Market Place
Acquisitions and spin-offs dominated headlines in 2019 and the tone was set very early with Bristol-Myers Squibb acquiring
New Jersey-based cancer drug company Celgene in a US$ 74 billion deal announced on
January 3, 2019. After factoring
in debt, the deal value ballooned to about US$ 95 billion, which according
to data compiled by Refinitiv, made it the largest healthcare deal on
record.
In the summer, AbbVie Inc,
which sells the world’s best-selling drug Humira, announced its acquisition of Allergan Plc, known for Botox and other cosmetic
treatments, for US$ 63 billion. While the companies are still awaiting
regulatory approval for their deal, with US$ 49 billion in combined 2019
revenues, the merged entity would rank amongst the biggest in the industry.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
The big five by pharmaceutical sales — Pfizer,
Roche, J&J, Novartis and Merck
Pfizer
continued
to lead companies by pharmaceutical sales by reporting annual 2019 revenues of
US$ 51.8 billion, a decrease of US$ 1.9 billion, or 4 percent, compared to
2018. The decline was primarily attributed to the loss of exclusivity of Lyrica in 2019,
which witnessed its sales drop from US$ 5 billion in 2018 to US$ 3.3 billion in
2019.
In 2018, Pfizer’s then incoming CEO Albert Bourla had mentioned that the company did not see the need for any large-scale M&A activity as Pfizer had “the best pipeline” in its history, which needed the company to focus on deploying its capital to keep its pipeline flowing and execute on its drug launches.
Bourla stayed true to his word and barring the acquisition of Array Biopharma for US$ 11.4 billion and a spin-off to merge Upjohn, Pfizer’s off-patent branded and generic established medicines business with
Mylan, there weren’t any other big ticket deals which were announced.
The
Upjohn-Mylan merged entity will be called Viatris and is expected to have 2020
revenues between US$ 19 and US$ 20 billion
and could outpace Teva to
become the largest generic company in the world, in term of revenues.
Novartis, which had
followed Pfizer with the second largest revenues in the pharmaceutical industry
in 2018, reported its first full year earnings after spinning off its Alcon eye
care devices business division that
had US$ 7.15 billion in 2018 sales.
In 2019,
Novartis slipped two spots in the ranking after reporting total sales of US$
47.4 billion and its CEO Vas Narasimhan continued his deal-making spree by buying New
Jersey-headquartered The Medicines Company (MedCo) for US$ 9.7
billion to acquire a late-stage cholesterol-lowering
therapy named inclisiran.
As Takeda Pharmaceutical Co was
busy in 2019 on working to reduce its debt burden incurred due to its US$ 62
billion purchase of Shire Plc, which was announced in 2018, Novartis also purchased
the eye-disease medicine, Xiidra, from the Japanese drugmaker for US$ 5.3 billion.
Novartis’ management also spent a considerable part of 2019 dealing with data-integrity concerns which emerged from its 2018 buyout of AveXis, the
gene-therapy maker Novartis had acquired for US$ 8.7 billion.
The deal gave Novartis rights to Zolgensma,
a novel treatment intended for children less than two years of age with the
most severe form of spinal muscular atrophy (SMA). Priced at US$ 2.1 million,
Zolgensma is currently the world’s most expensive drug.
However,
in a shocking announcement, a month after approving the drug, the US Food and
Drug Administration (FDA) issued a press release on
data accuracy issues as the agency was informed by AveXis that
its personnel had manipulated data which
the FDA used to evaluate product comparability and nonclinical (animal)
pharmacology as part of the biologics license application (BLA), which was
submitted and reviewed by the FDA.
With US$
50.0 billion (CHF 48.5 billion) in annual pharmaceutical sales, Swiss drugmaker
Roche came in at number two position in 2019
as its sales grew 11 percent driven by
its multiple sclerosis medicine Ocrevus, haemophilia drug Hemlibra and cancer medicines Tecentriq and Perjeta.
Roche’s newly introduced medicines generated US$ 5.53 billion (CHF 5.4 billion) in growth, helping offset the impact of the competition from biosimilars for its three best-selling drugs MabThera/Rituxan, Herceptin and Avastin.
In late 2019, after months of increased
antitrust scrutiny, Roche completed
its US$ 5.1 billion acquisition of Spark Therapeutics to strengthen its presence in
gene therapy.
Last year, J&J reported almost flat worldwide sales of US$ 82.1 billion. J&J’s pharmaceutical division generated US$ 42.20 billion and its medical devices and consumer health divisions brought in US$ 25.96 billion and US$ 13.89 billion respectively.
Since J&J’s consumer health division sells analgesics, digestive health along with beauty and oral care products, the US$ 5.43 billion in consumer health sales from over-the-counter drugs and women’s health products was only used in our assessment of J&J’s total pharmaceutical revenues. With combined pharmaceutical sales of US$ 47.63 billion, J&J made it to number three on our list.
While the sales of products like Stelara, Darzalex, Imbruvica, Invega Sustenna drove J&J’s pharmaceutical business to grow by 4 percent over 2018, the firm had to contend with generic competition against key revenue contributors Remicade and Zytiga.
US-headquartered Merck, which is known as
MSD (short for Merck Sharp & Dohme) outside the United States and
Canada, is set to significantly move up the rankings next year fueled by its
cancer drug Keytruda, which witnessed a 55
percent increase in sales to US$ 11.1 billion.
Merck reported total revenues of US$ 41.75 billion and also
announced it will spin off its women’s health drugs,
biosimilar drugs and older products to create a new pharmaceutical
company with US$ 6.5 billion in annual revenues.
The firm had anticipated 2020 sales between US$ 48.8 billion and US$ 50.3 billion however this week it announced that the coronavirus pandemic will reduce 2020 sales by more than $2 billion.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Humira holds on to remain world’s best-selling drug
AbbVie’s acquisition of Allergan comes as the firm faces the expiration of patent protection for Humira, which brought in a staggering US$ 19.2 billion in sales last year for
the company. AbbVie has failed to successfully acquire or develop a major new
product to replace the sales generated by its flagship drug.
In 2019, Humira’s US revenues increased 8.6 percent to US$ 14.86 billion while internationally, due
to biosimilar competition, the sales dropped 31.1 percent to US$ 4.30 billion.
Bristol Myers Squibb’s Eliquis, which is also marketed by Pfizer, maintained its number two position
and posted total sales of US$ 12.1 billion, a 23 percent increase over 2018.
While Bristol Myers Squibb’s immunotherapy treatment Opdivo, sold in partnership with Ono in Japan, saw sales increase from US$ 7.57 billion to US$ 8.0 billion, the growth paled in comparison to the US$ 3.9
billion revenue increase of Opdivo’s key immunotherapy competitor Merck’s Keytruda.
Keytruda took the number three spot in drug sales that
previously belonged to Celgene’s Revlimid, which witnessed a sales decline from US$ 9.69 billion to US$ 9.4 billion.
Cancer treatment Imbruvica, which is marketed
by J&J and AbbVie, witnessed a 30 percent increase in sales. With US$ 8.1
billion in 2019 revenues, it took the number five position.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Vaccines – Covid-19 turns competitors into partners
This year has been dominated by the single biggest health emergency in years — the novel coronavirus (Covid-19) pandemic. As drugs continue to fail to meet expectations, vaccine development has received a lot of attention.
GSK reported the highest vaccine sales of all drugmakers with
total sales of US$ 8.4 billion (GBP 7.16 billion), a significant portion of its
total sales of US$ 41.8 billion (GBP 33.754 billion).
US-based Merck’s vaccine division also reported a significant increase in sales to US$ 8.0 billion and in 2019 received FDA and EU approval to market its Ebola vaccine Ervebo.
This is the first FDA-authorized vaccine against the deadly virus which causes
hemorrhagic fever and spreads from person to person through direct contact with
body fluids.
Pfizer and Sanofi also reported an increase in their vaccine sales to US$ 6.4
billion and US$ 6.2 billion respectively and the Covid-19 pandemic has recently
pushed drugmakers to move faster than ever before and has also converted
competitors into partners.
In a rare move, drug behemoths — Sanofi and GlaxoSmithKline (GSK) —joined hands to develop a vaccine for the novel coronavirus.
The two companies plan to start human trials
in the second half of this year, and if things go right, they will file
for potential approvals by the second half of 2021.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Our view
Covid-19 has brought the world economy to a grinding halt and shifted the global attention to the pharmaceutical industry’s capability to deliver solutions to address this pandemic.
Our compilation shows that vaccines and drugs
for infectious diseases currently form a tiny fraction of the total sales of
pharmaceutical companies and few drugs against infectious diseases rank high on
the sales list.
This could well explain the limited range of
options currently available to fight Covid-19. With the pandemic currently infecting
over 3 million people spread across more than 200 countries, we can safely
conclude that the scenario in 2020 will change substantially. And so should our
compilation of top drugs for the year.
View Our Interactive Dashboard on Top drugs by sales in 2019 (Free Excel Available)
Impressions: 54752
https://www.pharmacompass.com/radio-compass-blog/top-drugs-and-pharmaceutical-companies-of-2019-by-revenues
#PharmaFlow by PHARMACOMPASS
29 Apr 2020
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This week, Phispers has news from across the world. While China is trying to speed up approval of drugs by accepting data from overseas trials, the US achieved record approval of generic drugs last fiscal. In India, pharma companies may face legal action for releasing effluents into a lake in Hyderabad that killed thousands of fish last week. In France, a reformulated thyroid pill from Merck led to severe side effects in patients. And, there was more bad news for Israel’s Teva as its competitors won approvals from regulators in the US and Europe to market cheaper versions of its blockbuster multiple sclerosis drug — Copaxone.
Data-integrity uncovered in AstraZeneca’s US$ 4 billion Acerta buy
In
February 2016, pharma giant AstraZeneca had invested US$ 4
billion in acquiring 55 percent stake in Acerta Pharma — a biopharmaceutical company based in the Netherlands and the US. The acquisition provided AstraZeneca with a cancer drug under clinical trials — acalabrutinib.
An AstraZeneca press release issued at the time of acquisition had said: “Acalabrutinib is a highly selective, irreversible, second generation BTK inhibitor, with approximately 1,000 patients treated to date in clinical studies across the entire development programme.”
But
the acquisition brought some bad news for AstraZeneca last week, as a story published in Retraction
Watch said one of Acerta’s former researchers had falsified early data on acalabrutinib.
“The data, published as an abstract in August 2015 in the journal Cancer Research, reported a therapeutic benefit of acalabrutinib in a mouse model of pancreatic cancer,” the report said. The drug is now in human trials.
Additional
trials published in the New England Journal of Medicine and Blood in 2015 showed acalabrutinib had “promising safety and efficacy profiles in patients” with relapsed chronic lymphocytic leukemia.
However,
investigation into the data underlying the 2015 abstract revealed some of it
was falsified. As a result, the journal retracted on the abstract.
Interestingly
a few weeks ago, acalabrutinib had won breakthrough
therapy status at the US Food and Drug Administration (US FDA) along with an
accelerated review plan for its first approval.
However,
all news was not bad news for AstraZeneca. Its innovative treatment for a type of lung cancer won “breakthrough” designation by the US FDA. The endorsement is for therapy Tagrisso for use in the US by
patients with previously-untreated non-small cell lung cancer and a genetic
mutation known as EFGR. This paves the way for fast-track approval of the drug.
Dead fish in Hyderabad leads to pharma majors being booked
for fouling lake water
Pharmaceutical companies in India — such as Hetero Pharma, Aurobindo Pharm, Mylan, SMS Pharma, Vantec and Sriram — that have their manufacturing facilities in Kazipally industrial area and Industrial Development Area (IDA) have been booked under a case for “fouling water of public spring or reservoir”.
This
happened last week after the Gandigudem lake, which is barely a few
meters away from Hyderabad's Outer Ring Road (ORR), reported hundreds of bloated, dead fish washed ashore after it rained heavily. The 266-acre lake is
situated near the IDA.
The
lake has been plagued with pollution for a while now. According to news reports, the Pollution
Control Board (PCB) had found traces of chloromethane, a solvent used in the
pharma industry, in the samples of the water and dead fish collected from the
lake. The diluted traces of the chemical in the lake confirm
contamination.
Officials
said that 230,000 fish had been washed ashore within a span of two days,
causing heavy loss to the fishermen dependent on the lake. According to an
official, the fish lost was worth US$ 230,038 (Rs 15 million)
These
companies have been booking under Section 277 (fouling water of
public spring or reservoir) and Section 278 (making atmosphere noxious to
health) of the Indian Penal Code.
A
video of a news report on the story can be viewed here.
China to accept data from overseas trials in order to speed up drug
approvals
China plans to speed up approval of drugs, and will accept data from overseas clinical trials in order
to facilitate that. The move could be a boon for international drugmakers as
well as for patients who often face lengthy delays for new medicines to reach
the market.
China has approved just over 100 innovative new drugs in the last 15 years — about a third of the drugs approved in the developed markets. This is the key reason behind the country taking this step to speed up drug approvals.
The move also seeks to address high medicine costs, and improve access to healthcare for China’s 1.4 billion population.
The
Chinese Cabinet will also look into improving the protection of medical
intellectual property and boost the number and quality of clinical trial
testing centers in China. However, the proposals contained no timeline for
implementation.
In
March this year, China had proposed ways to speed up approvals for
imported drugs, including reforming clinical trial requirements.
Merck’s French reformulation of most prescribed US drug leads to severe side effects
Popular thyroid drug Levothyroxine reportedly received many complaints of severe side effects from patients in France. The drug works as a stand-in for the hormone thyroxine in patients suffering from hypothyroidism, a condition that affects the body’s metabolism.
According
to a Reuters report, French police searched German drugmaker Merck KGaA’s plant in Lyon last week
as part of a probe into complaints by patients about changes to its thyroid
drug Levothyrox.
In
March this year, Merck had removed lactose from Levothyrox to make it easier to
tolerate and replaced it with citric acid and mannitol, a type of sugar
alcohol. The new formulation had been requested by the French medicines
regulator ANSM in 2012. According to patients, this resulted in severe side
effects such as memory loss, hair loss, weight gain and palpitations.
Around
3 million people in France, 80 percent of them women, use Levothyrox. According
to a Medscape article, levothyroxin is also the most prescribed drug in the US. The prescriptions for
Levothyroxine (in the US) stood at 112 million in 2012 and 123 million in 2016.
The drug was far ahead of the number two drug on the list (Lisinopril — with 99 million prescriptions in 2012 and 110 million in 2016).
Last
month, a prosecutor in Marseille had launched a probe into whether Merck had deceived patients with the change in the drug’s formula. Since then, Merck has restored the original drug to the market.
Teva fights to hold market share as competitors receive nod for
its blockbuster drug
Bad
news from Israeli generic drug giant Teva Pharmaceutical Industries doesn’t seem to relent. Last week, Teva was taken unawares when its competitors won approvals from regulators in the
US and Europe to market cheaper versions of its flagship Copaxone drug for multiple
sclerosis.
The launch of the competing products will result in “significant declines” in Teva’s largest product effective this year, Moody’s Investors service said in a note.
On
October 3, Mylan said it received approval from the US FDA for the marketing of generic versions of Teva’s Copaxone (glatiramer acetate) in 40 mg and 20 mg dosages. Mylan said it would
start shipping the generic version immediately.
According
to Bernstein analyst Ronny Gal, Mylan is serving up 25 to 30 percent discounts versus the “prevailing price” on Teva’s Copaxone and Teva is countering it, he added.
Analysts
had written off Mylan’s long-delayed generic Copaxone until next year. The
approval last week surprised analysts and investors.
Two
days later, Alvogen said it had received an
approval from European regulators to market the 40 mg dose of generic Copaxone
in Europe. Alvogen has been selling the 20 mg dose of the drug in Europe.
These approvals could mean a “downside” to both revenue and profit estimates for 2018, Citi’s Liav Abraham said.
Generic drug approvals in US hit all time high; Indian firms
corner large chunk
The US FDA
approved a record 763 generic drugs
in the US fiscal year that ended on September 30, 2017. Amongst these, Indian
companies accounted for nearly 40 percent of the approvals, a news report
published in the Mint said. The regulator also gave 174 tentative
approvals during 2016-17.
In comparison, the
US FDA had approved 651 generic drugs last year, the latest Activities Report
of the Generic Drug Program of the FDA said.
Indian companies received a total of 295 product approvals in 2016-17. Amongst them, “the pace of drug approvals was strong for Aurobindo Pharma, Cadila Healthcare and Lupin,” the Mint report added.
As per the FDA
report, total filings of abbreviated new drug applications (ANDAs) for generic
drugs with the US FDA rose to 1,292 in 2016-17 from 852 a year ago.
According to
analysts, the increasing number of product approvals and filings indicate an
increase in competitive intensity in the US, which is a major market for many
Indian drug companies. This would also result in more pressure on drug pricing.
Impressions: 3243
https://www.pharmacompass.com/radio-compass-blog/dead-fish-in-hyderabad-puts-pharma-majors-under-scrutiny-false-data-uncovered-in-astrazeneca-us-4-billion-buy
#PharmaFlow by PHARMACOMPASS
12 Oct 2017
This week, Phispers brings you the latest from the world of biosimilars, with Samsung Bioepis tying up with Japan’s Takeda, Biocon transferring its biosimilar business to a subsidiary, and South Korea’s Celltrion denying reports that its proposed biosimilar of Herceptin could face delays in Europe. Teva faced yet another bad week, with two Congressmen in the US attacking it over price increases of its multiple sclerosis drug. Meanwhile, Mylan and J&J will have to pay millions of dollars for cases against them. In vaccines, GSK faces flak for shortage of its Hepatitis B vaccine in the UK. And Pfizer won a pneumonia vaccine patent battle in India.
Biocon transfers biosimilar business to subsidiary; Samsung
Bioepis ties up with Takeda
A lot has been going on in the world of biosimilars. Last week, in
a stock exchange filing, Biocon said it has withdrawn the dossier for the biosimilar products — Fulphila® (pegfilgrastim) and Ogivri® (trastuzumab). Since the
approval of its trastuzumab and pegfilgrastim applications would require re-inspection of its drug product facility (for these products), the “request of withdrawal of the dossiers and re-submission is part of the EMA procedural requirements linked to this reinspection…,” Biocon said in the statement.
The announcement came a fortnight before
the FDA was supposed to take a decision on the trastuzumab application.
This week, the board of Biocon approved
the transfer of the biosimilar business of the company to Biocon Biologics India, a step-down subsidiary of the company, subject to the consent of its shareholders. The transfer of the biosimilar business has been done by way of a ‘slump sale’ as a going concern — wherein a sale is done for a lump sum consideration without values being assigned to the individual assets and liabilities.
Concerns also emerged over Biocon’s Herceptin
biosimilar competitor — Celltrion — as it denied a news report that its proposed biosimilar of Herceptin (a breast cancer drug) could face delayed European approval due to late submission of data. With global sales of around US$ 7 billion a year, Herceptin is one of Roche’s best-selling drugs.
According to the Celltrion, the European Medicines Agency
(EMA) found no lapses during a pre-approval inspection of its product site and drug substance Herzuma — its copy version of Roche’s Herceptin. The South Korea-headquartered biopharmaceutical firm also managed to hand in the documents that it was required to provide after inspection.
“We don’t expect any major changes in approval procedures although the inspection date had been pushed back a little because of differing schedules,” a Celltrion official said. There was news that the EMA could postpone approval of Herzuma to 2018 as the company failed to submit documents on time. However, it seems like Celltrion’s Herzuma may get EMA’s nod this autumn.
Any delays in approval procedures for Herceptin biosimilar candidates could have an impact on other drug makers eyeing the US$ 2 billion EU market for the original drug including another South Korean biosimilar firm — Samsung Bioepis — which filed for EU approval in September 2016.
The biosimilar industry is keeping a close
watch on which of the two South Korean firms is the first to get the nod for
its Herceptin biosimilar, after Biocon withdrew its application last week.
Meanwhile, Samsung Bioepis unveiled a new alliance this week — with Japan’s Takeda. Together with Takeda, Samsung Bioepis hopes to accelerate the development of effective therapies. The Japanese firm
has been open to devising new alliances that will share the risk in order to
broaden its overall drug development work.
More bad news for Teva as US
Congressmen attack pricing of its flagship therapy
Two US Congressmen accused Teva of hiking the price of its flagship multiple sclerosis (MS) drug — Copaxone (glatiramer acetate) — by more than 1,000 percent since 1996. Copaxone generated US$ 4.22 billion in sales last year.
The Congressmen — Elijah Cummings and Peter Welch — want to fully investigate Teva’s pricing practices, while also calling out firms such as Novartis, Bayer and Biogen.
According to the Congressmen, a year’s worth of 20 mg Copaxone was priced at US$ 8,292 in 1996. This increased to US$ 51,315 in 2012 and US$ 91,401 in 2017. Lack of generic competition permitted Teva to increase the price of the drug to such high levels.
Cummings and Welch said they were launching an investigation into
why prices for MS treatments have nearly quintupled since 2004. According to
the National Multiple Sclerosis Society, the average annual cost of MS therapy
rose to US$ 78,000 in 2016 from US$ 16,000 in 2004.
Meanwhile, Teva is planning to tie up with other drugmakers to fund some
of its development pipeline as it struggles with debts and expiring patents.
Teva needs funds to develop new drugs, and striking alliances with big pharma
players is one way of doing that.
Earlier this month, Teva reported a steep
drop in second-quarter earnings. Teva is saddled with debts of around US$ 35
billion, which it took on when it acquired Actavis (Allergan’s generic business) for US$ 40.5 billion last year.
Sanofi
gains millions via Mylan’s EpiPen settlement; J&J to pay US$ 417 million in baby powder case
Last week, Mylan NV and the US Justice Department finalized a US$ 465 million
settlement to resolve claims that Mylan had defrauded taxpayers and overcharged
the government by misclassifying its EpiPen emergency allergy treatment as a generic drug.
EpiPen had become the center of a drug
price-hikes controversy last year.
The probe into the price of EpiPen followed
a whistleblower lawsuit filed under the False Claims Act that rival drugmaker Sanofi SA filed in 2016. As a result of the settlement, Sanofi will
receive US$ 38.7 million as a reward, authorities said.
Meanwhile, lawmakers in the US say the settlement wasn’t tough enough. According to Democratic Senator Richard Blumenthal of Connecticut, the agreement was a “feeble fraction” of the US$ 1.27 billion that a government report found taxpayers may have overpaid for EpiPen over the last decade.
Mylan had acquired EpiPen in
2007. It is a handheld device that treats life-threatening allergic reactions
by automatically injecting a dose of epinephrine. Mylan had raised the price of a pair of EpiPens to US$ 600,
from US$ 100 in 2008.
J&J baby powder case: A US court directed Johnson & Johnson to pay US$ 417 million to a woman who alleged that the company’s baby powder causes ovarian cancer.
In her lawsuit, 63-year-old Eva Echeverria
had claimed that she used the talcum powder from the 1950s till 2016, and
developed ovarian cancer in 2007. Echeverria alleged that J&J failed to warn consumers about the risks involved in using
their talcum powder. The court awarded the woman US$ 68 million as compensatory
damages, and US$ 340 million as punitive damages.
Hikma raises price of diarrhea drug by 400
percent; Trump signs user fee law
Last
week, the US saw another price-gouging incident. The US subsidiary of Hikma Pharmaceuticals Plc raised the price of a common diarrhea drug by more than 400 percent. Known as West-Ward Pharmaceuticals, the US division of Hikma is also charging more
for five other medicines.
According
to a Financial Times report, the average
wholesale price of a 60 ml bottle of liquid atropine-diphenoxylate,
a common diarrhea drug also known as Lomotil, went from about US$ 16 a bottle
to US$ 84.
FDA Reauthorization Act: Last week, President
Donald Trump signed the FDA Reauthorization Act of 2017 into law. With this, the FDA saw the end of a
two-year long process that was threatening to disrupt its operations.
The law comes at a time when the FDA, under
the new commissioner Scott Gottlieb, is approving generics at a record pace.
Though the legislation had been passed by both the houses of the Congress, it faced a number of threats, including Trump’s intent to fund the FDA entirely with user fees from companies. Between 2018 and 2022, the FDA is expected to collect US$ 9 billion in fees — US$ 8 billion for prescription drugs and US$ 1 billion for devices — based on the fee level set in the Senate bill.
GSK
faces flak for Hep B vaccine shortage in
UK;
Pfizer wins vaccine patent in India
In
the UK, drug giant GlaxoSmithKline faced flak and an increasing number of questions over shortages of its vaccine for the deadly liver disease hepatitis B. The shortage of this vaccine in the UK has led to rationing.
Earlier this month, Public Health England (PHE) took the rare step of advising doctors to limit prescription of the vaccine, citing a “global shortage”.
This comes at a time when GSK’s supplies of the vaccine to the US appear to be unaffected. The disparity has led to suggestions from liver disease campaigners that GSK may be “prioritizing” the massive American market.
Hepatitis B is considered a “silent killer” leading to 900,000 global deaths a year. However, the disease is more prevalent in the developing world and is rare in the UK. Meanwhile, the World Health Organisation (WHO), has said there is no global shortage of the vaccine. The WHO is responsible for monitoring stocks of vaccines worldwide.
In
India, Pfizer Inc was granted a patent for its powerful pneumonia vaccine —Prevenar 13.
The
decision bars other companies from making cheaper copies of the vaccine and
allows Pfizer to exclusively sell it
in India until 2026.
The
patent came as a blow to some health groups that said this would put the
treatment out of reach of thousands in poorer nations. The move comes at a time
when India is facing increased pressure from the US to tighten its patent laws.
In a report published in June this year, the United States Trade Representative
expressed concerns over India’s intellectual property laws.
India has the largest number of pneumonia cases, and for Pfizer, this is a big gain. The decision also has international implications, as several poorer nations rely on India’s robust pharmaceutical industry to supply cheaper copies of medicines and vaccines.
FDA to start
sharing full inspection reports with European regulators
This week, the European Commission (EC), the US Food and Drug Administration (FDA)
and the European Medicines Agency (EMA) signed a new confidentiality commitment that allows the FDA to
share non-public and commercially confidential
information, including trade secret information relating to
inspections with European regulators.
In
March 2017, the United States and the European Union (EU) finally announced that they will be able to utilize each other’s good manufacturing practice (GMP) inspections of pharmaceutical manufacturing facilities.
The
deal is expected to enable the US Food and Drug Administration (FDA) and the EU
to avoid duplication of drug inspections, lower inspection costs and enable
regulators to devote more resources to other parts of the world where there may
be greater risk.
This confidentiality commitment is a step in the ongoing
implementation of the mutual recognition of inspections
program.
Impressions: 4148
https://www.pharmacompass.com/radio-compass-blog/fda-to-share-full-inspection-reports-with-eu-difficult-week-for-teva-j-j-mylan
#PharmaFlow by PHARMACOMPASS
24 Aug 2017
This week, Phispers brings you the high-pitched drama from President Trump’s American Manufacturing Council, with Merck CEO Ken Frazier leading the pack of CEOs who abandoned it over the Charlottesville unrest, even as J&J’s CEO said he’ll stay on. But then, Trump disbanded the council.
We bring you
news on more generic companies in distress due to a drop in their business in
the US and compliance problems. Meanwhile, companies like Intas and Aurobindo
Pharma from India and Fosun from China are looking for growth via acquisitions.
And Softbank has invested US$ 1.1 billion in Roivant. Read on.
Merck CEO’s Trump council resignation over ‘intolerance’ has others follow; council disbanded
The US President Donald Trump’s American Manufacturing Council has been in the news for the last few days. First, Merck CEO Kenneth Frazier resigned from the council, after urging American leaders to reject expressions of ‘hatred, bigotry and group supremacy’ on Twitter.
In a statement, Trump had blamed “many sides” for the violence in Charlottesville, Virginia, over the last weekend. A white nationalist rally had turned violent in the city when a car rammed into many people who were protesting peacefully against the demonstration. White supremacists and other hate groups had assembled in the city to protest the removal of a statue of Confederate General Robert E. Lee.
Trump has since faced widespread criticism for not specifically denouncing the white supremacists. Following Frazier’s resignation, many CEOs — including Intel
Corp’s Brian Krzanich, Under
Armour Inc’s Kevin
Plank and AFL-CIO chief Richard Trumka — quit Trump’s council over his ‘response to the Charlottesville
violence’.
Though Frazier
said he was taking a stand “against intolerance and extremism”, Trump mocked at him on Twitter, and said he will now “have more time to LOWER RIPOFF DRUG PRICES!” Later, Trump did condemn the hate groups, but it seemed too little to late.
Only three
weeks back, Trump had called Frazier a “business genius” and a “great, great business leader” and had thanked Merck for investing in American jobs. Frazier is one of the few African-Americans to head a Fortune 500 company.
Meanwhile, on
Tuesday, Johnson & Johnson’s CEO Alex Gorsky said he isn’t abandoning Trump’s council. In a statement, Gorsky said he’ll stick with the council as a way to express “the values of Our Credo as crucial public policy is discussed and developed.” He said J&J is “an important voice on healthcare.”
However, as the CEO resignations
continued to mount, Trump tweeted, “Rather than putting pressure on the business people of the Manufacturing Council & Strategy & Policy Forum, I am ending both. Thank you all!”
Trump made
the announcement on Twitter, less than an hour after one of the groups was planning to inform
the White House that it would disband, a CNBC report said.
Dr. Reddy’s fails EU GMP inspection; can’t export to EU until it clears next inspection
Less than two
months after providing positive inspection updates with regard to the status of its
manufacturing compliance, Dr. Reddy’s Laboratories (DRL)
failed a European cGMP manufacturing inspection last week. The inspection, by the German regulatory authority, at DRL’s FTO 2 finished formulation plant (situated in Hyderabad) uncovered critical deficiencies.
The inspectors concluded that the ‘essential elements of the Pharmaceutical Quality System’ were not effective. Due to this, the plant will not be able to make any further dispatches to the European Union until the next inspection, “to be initiated by an invitation from betapharm,” DRL said in a filing.
Betapharm Arzneimittel GmbH is DRL’s wholly-owned subsidiary in Germany and the Hyderabad plant produces tablets and capsules.
Previously, PharmaCompass
had observed that the inspection focus of regulators has moved beyond audit trails. In the case of DRL, the inspectors found that out of specification (OOS) results were “systematically invalidated in hundreds of cases”.
The integrity of the batch manufacturing/packaging record at the Hyderabad facility was also questioned. The absence of recording “negative events” on the “clean” batch manufacturing records prevented successful investigation into market-complaints.
In addition to
the integrity of the cleaning being questioned, the design, condition and maintenance of rooms and
equipment were also major concerns at DRL. The inspectors found dirty rooms and
equipment, along with unsuitable doors and dispensing equipment for
manufacturing.
Generics in distress: Sun reports its first loss in 12 years; Mylan cuts
forecast
Generic
drugmakers have seen their US businesses plummet as the US Food and Drug
Administration (USFDA) has stepped up product approvals, ushering in more
competition and prompting a steady erosion in prices.
As a result,
generic drug stocks have been under pressure. Last week, Phispers
reported on how Teva Pharmaceutical had reduced its earnings goal. Well, companies like Mylan NV and Sun Pharmaceutical Industries have
joined the pack by reporting lackluster quarterly results and cutting
guidance.
After a gap of 12 years or more, Sun Pharma reported its first quarterly loss last week, after it
settled an antitrust case in the US. Sun Pharma paid US$ 148 million (INR 9.5
billion) to plaintiffs including Canadian rival Apotex in July to settle an antitrust
lawsuit in the US over sleep-disorder drug modafinil.
Sun, which is India’s biggest drugmaker, posted a total loss of US$ 66.3 million (INR 4.25 billion) in the three months ended June 30, 2017.
Last week, Mylan also said it is likely to see a decline in its profitability due to delays in the launch of key new drugs and erosion in the prices for generics in the US.
Though the FDA is speeding up generics approvals, it’s just not speeding up the ones that Mylan badly needs.
Mylan said it plans to remove copies of big drugs like Copaxone from Teva and Advair from GlaxoSmithKline—from its 2017 guidance, pushing them into 2018. It now expects revenues to hit between US$ 11.5 billion and US$ 12.5 billion for the year, down from a previous range of US$ 12.25 billion to US$ 13.75 billion.
Chip Davis, CEO of the Association of Accessible Medicines — a trade group for generic and biosimilar drugs — said some of the (demand-supply) imbalances in the generic marketplace haven’t happened overnight. But the “reality is that the sustainable, robust competitive market is at risk now.” He expects generic drugmakers to continue to feel the pressure, amid declining prices and flat revenues.
From June 2016
to June 2017, the number of generic prescriptions is nearly flat, with an
increase of only around 1 percent; while revenue is down 12 percent, Davis
said.
However, one
generic company that bucked the trend was Perrigo. It reported US$ 1.24 billion in sales and adjusted
earnings of US$ 1.22 per share, topping the consensus for US$ 1.18 billion and
92 cents, respectively.
However, this performance too did not come on the back of generics — Perrigo’s generic business declined 13 percent
year-on-year. The company performed well due to its consumer business.
India’s Intas and Aurobindo, PE player SK Capital and China’s Fosun in acquisition mode
Even during
these bad times for generics, some pharma companies are on the prowl. For
instance, Ahmedabad-based Intas Pharmaceuticals is on the look out for buying into a larger piece of Israeli-drugmaker Teva’s existing operations in Europe. Last year, it had bought out Teva’s UK and Ireland assets.
Intas — with Temasek and Chrys Capital as its investors — is bidding for Teva’s women's health, oncology and pain management divisions in Europe for US$ 1.5 billion. The company has reportedly reached out to several Indian and global banks, such as ICICI, Axis, Citi, Bank of Tokyo Mitsubishi UFJ, HSBC among others, to finalize the financing before putting in a bid by the month-end. If successful, this will be the largest cross-border M&A involving an Indian pharma company.
PharmaCompass has been routinely covering the troubles at Teva, the world’s largest maker of generic drugs. Teva plans to sell off its assets, in order to reduce its US$ 36 billion debt.
There is another company that Intas has set its eyes on — Mallinckrodt's US generic business. According to a news report, India’s Aurobindo Pharma and Intas are in the race to buy
UK-based Mallinckrodt’s generic drugs business in the US
valued at US$ 2 billion.
Once complete, this will be the biggest-ever overseas acquisition made by an
Indian drug company.
The generic
business of Mallinckrodt generates sales of around US$ 1 billion. The companies have submitted an initial bid for Mallinckrodt’s generic business, which has been up for sale for the last couple of months.
Meanwhile, US specialty drugmaker — Arbor Pharmaceuticals — too is up for grabs. And amongst the bidders for a stake in Arbor are companies like Fosun International Limited’s healthcare business and Shanghai Pharmaceuticals Holding. The two companies are competing to buy a stake of at least 20 to 30 percent, sources said. The holding in the Atlanta-based Arbor could fetch around US$ 600 to US$ 700 million.
In the US, SK
Capital, a private investment firm focused on specialty materials, chemicals
and pharmaceuticals, said it has signed a definitive agreement to acquire Perrigo API, the active pharmaceutical ingredients (API) business
of Perrigo Company Plc.
The two
parties have agreed to enter into a long-term supply agreement for Perrigo API
to supply multiple existing commercial and pipeline APIs to Perrigo. The
transaction is expected to close during the last quarter of this year.
Softbank invests US$ 1.1 billion in Vivek Ramaswamy’s abandoned drug venture —Roivant
Last week, Roivant
Sciences announced that Japanese conglomerate — SoftBank Group — is leading a US$ 1.1 billion investment to fund its expansion. SoftBank is the largest
private financier in healthcare.
Roivant was
founded by Vivek Ramaswamy, a 32-year old American entrepreneur who began his
career as an investor in the biotechnology sector. Roivant is a holding company
with companies like Axovant Sciences and Myovant Sciences under its umbrella,
along with private-subsidiaries like Dermavant, Urovant and Enzyyant.
According to Endpoints
News, SoftBank’s US$ 1.1 billion mega-investment in Roivant won’t likely be its last in biotech. Quoting reports, it says SoftBank group’s global US$ 100 billion equity fund has begun a recruitment campaign for scientists with an eye to backing more companies that use new data technology to identify drugs with solid development potential.
Ramaswamy’s business model has relied on therapies that have been taken off the shelves of some big players. Back in December 2014, Ramaswamy had bought an old Alzheimer’s drug that GSK had dropped for US$ 5 million. Six months after purchasing the compound from GSK, and without doing any clinical development, the drug resulted in the biggest biotech IPO ever for Axovant, which got valued at US$ 2 billion. Since then, Ramaswamy has been setting up more companies.
Biocon,
Mylan suffer another setback as European biosimilar applications are withdrawn
Last month, PharmaCompass broke the story about Biocon’s biosimilar
program suffering a serious setback as a current Good Manufacturing Practices (cGMP) inspection by the French health agency — ANSM — in March 2017 of its drug product site located in Bengaluru, India, uncovered 35 deficiencies, of which 11 were deemed major.
The inspection was conducted on behalf of the European Medicines Agency (EMA) by the ANSM as a pre-approval inspection for the drug product manufacturing activities of the following (three) biosimilar products — Fulphila® (pegfilgrastim), Ogivri® (trastuzumab) and Semglee® (insulin glargine).
This week, in
a stock exchange filing, Biocon said it has withdrawn the dossier for two of these products. Since the approval of its trastuzumab and pegfilgrastim applications would require a re-inspection of its drug product facility (for these products), the “request of withdrawal of the dossiers and re-submission is part of the EMA procedural requirements linked to this reinspection…,” Biocon said in the statement.
The
announcement comes two weeks before the FDA is supposed to take a decision on
the trastuzumab application.
Although Roche’s European patents
on Herceptin (trastuzumab) expired in 2014, it is still the third-biggest drug,
with 2016 sales of US$ 6.7 billion (CHF 6.8 billion) for the Swiss Group.
Until the news of the
ANSM inspection surfaced, Mylan and Biocon were expected to be the first to bring a Herceptin biosimilar to market.
Impressions: 4444
https://www.pharmacompass.com/radio-compass-blog/dr-reddy-s-fails-eu-inspection-trump-disbands-business-councils-after-merck-ceo-and-others-quit-it-over-intolerance
#PharmaFlow by PHARMACOMPASS
17 Aug 2017
This week, Phispers brings you news on GSK, whose new CEO is planning a slew of initiatives to make the British drug giant more competitive. This means more challenges for Luke Miels, AstraZeneca CEO Pascal Soriot’s former deputy who is joining GSK as head of pharma division. Soriot, on the other hand, put all rumors to rest in a memo to his staff. In other news, Donald Trump unveiled a glass vial project that will create more jobs in America. And Teva announced job cuts in Israel. While Momenta-Sandoz lost a case to Amphastar.
GSK overhaul begins under new CEO; AZ’s Soriot puts (Teva) rumors to rest in a memo
Pascal Soriot, chief
executive of AstraZeneca, put all rumors to rest and told his
staff that he expects to work together with them and see the company succeed. A report in the Israeli media earlier this month had
said Soriot was in talks to join Teva. Last week, PharmaCompass reported
that Soriot had dropped the offer.
Though he did not mention Teva, in a memo, Soriot said: “Together, we are poised to achieve something remarkable and that few thought possible…Nothing can break the momentum you have established, and certainly not rumors.”
Soriot
is reportedly attending the European Society for Medical Oncology (ESMO)
annual meeting in Madrid in September, in case AstraZeneca has its clinical
data on its new immunotherapy medicine ready to present at the event.
Meanwhile, Soriot’s deputy, Luke Miels, is joining GlaxoSmithKline as head of its pharma
division. And if news reports are to be believed, employees are going to need courage to work under the Emma Walmsley,
the new CEO of the British drug giant.
Walmsley is looking for ways to make GSK more competitive. And in order to achieve that, she is pushing some functions and a lot of accountability into GSK’s three divisions. Their leaders will own the successes, as well as any failures.
According
to news reports, GSK is selling its Horlicks brand in the UK, shutting the Slough plant
where the malt drink is made and is abandoning a proposed US$ 457 million (£350 million) biopharmaceutical manufacturing plant in Cumbria.
Walmsley
also wants to improve drug research productivity, and wants GSK to have fewer but potentially more lucrative new drug launches in
the future. GSK is planning on scrapping more than 30 drug development programs and will focus 80
percent of its R&D budget on the top candidates in four therapeutic areas
and potentially exit the rare disease space.
Momenta-Sandoz lose case to Amphastar; AbbVie to
pay US$ 150m in damages
In
the US, Amphastar Pharmaceuticals won a case in a federal court against Momenta
Pharmaceuticals Inc and its partner Novartis AG’s Sandoz unit. The two had sought nearly
US$ 940 million in damages against Amphastar.
Momenta
and Sandoz had filed the lawsuit in 2011 after the US Food and Drug Administration (USFDA) had approved Amphastar’s generic version of Sanofi’s blockbuster Lovenox, an anticoagulant used to treat and
prevent blood clots.
The
two companies had accused Amphastar of infringing on a patent held by them,
through the production of a generic version of the blood-thinner Lovenox.
In
a statement, Momenta CEO Craig Wheeler said the company was disappointed and was considering its options, including a potential appeal. “We continue to believe in the importance of investing in innovative techniques for bringing products to market and protecting those innovations from unauthorized use,” he said.
Momenta
and Sandoz suffered a major setback earlier this year when Pfizer’s fill/finish manufacturing facility in
McPherson, Kansas, received a warning letter from the USFDA. The compliance
concern had been initially revealed by Momenta in a press statement as the
company, in collaboration with Sandoz, is developing a generic version of Teva’s
long-acting Copaxone® 40mg/mL (glatiramer acetate injection). Sandoz had tied up with Pfizer as its fill/finish manufacturing
partner.
Copaxone generated US$ 4.22 billion in sales last year.
Meanwhile,
a federal jury in Chicago found AbbVie Inc fraudulently misrepresented the risks of its testosterone replacement drug — AndroGel. The jury ordered AbbVie to pay US$ 150 million in punitive
damages.
A
lawsuit had been filed in 2014 against AbbVie by Jesse Mitchell and his wife.
The decision in the Mitchell case is the first in a series of test trials aimed
at helping plaintiffs and manufacturers of AndroGel assess the range of damages
and define a legal strategy and settlement options for such trials.
The jury said AbbVie was not “negligent or strictly liable” for a heart attack Mitchell suffered after taking AndroGel. However, it said AbbVie falsely marketed the drug. And, it did not award Mitchell compensatory damages for his injuries and losses.
Trump unveils glass vial project that is likely to
create 4,000 jobs in the US
Last
week, the US President Donald Trump announced an initiative to manufacture a
new kind of glass for injectable drug vials. Corning Inc is making a US$ 500 million
investment along with pharma giants Merck and Pfizer to manufacture these vials, which are
likely to create nearly 1,000 jobs at facilities in New York and New Jersey and another ‘yet to be announced’ site in southeastern USA.
This initiative was part of Trump's ‘Made in America’ week, during which he showcased America-made products. Trump also defended his administration’s ‘America First’ policies. He was joined by the
CEOs of Corning, Merck and Pfizer.
Trump said the deal could eventually result in a total investment of US$ 4 billion and create around 4,000 jobs. “This initiative will bring a key industry to our shores that for too long has been dominated by foreign countries. We’re moving more and more companies back into the United States,” Trump said.
According
to Trump, the glass is called Valor Glass and is a “substantial improvement” in
quality over existing products. It has superior strength and is more
damage-resistant.
In Israel, Teva pulls out the job axe; Japan’s Mitsubishi Tanabe buys Neuroderm
Teva
Pharmaceutical Industries recently announced that it is beginning negotiation
with the labor groups in Israel. It is expected to cut 300 to 350 workers and managers at production sites in
Histadrut and Ramat Hovav in the coming months.
This move will be yet another step towards Teva’s restructuring and business focus, aimed at bolstering the competitiveness of its sites in Israel.
Post
this announcement, Histadrut called a work dispute, which will permit employees
to strike in 14 days time. Teva currently has 7,000 employees in Israel.
Histradrut spokesman Yaniv Levy said: “We will not accept any unilateral measure in which workers are laid off at Teva. We expect the company’s management to act responsibly, and not to involve Teva’s plants in Israel in a series of conflicts that will escalate labor relations.”
Meanwhile,
Japan's Mitsubishi Tanabe Pharma has agreed to buy Israeli drug maker
Neuroderm for US$
1.1 billion in cash as part of a strategy to grow its business in the US.
Mitsubishi Tanabe said it is particularly attracted by Neuroderm’s Parkinson’s disease drug that is in advanced clinical trials in the US and Europe and is likely to be launched in 2019.
A minor molecule twist could be the
solution to cancer that killed Steve Jobs
Last
week, a nuclear medicine targeted at the type of cancer that killed former
Apple Inc co-founder and CEO Steve Jobs got a nod from the European Medicines
Agency (EMA), boosting prospects for its developer — Advanced Accelerator Applications (AAA).
The EU drugs regulator said its Committee for Medicinal Products for Human Use (CHMP) had recommended the product — Lutathera (lutetium 177 dotatate). This emerging treatment targets gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. The drug is likely to get a full approval in the coming two months.
Stefano Buono, chief executive officer of AAA, said
the company was also ready to re-file its application for US marketing approval
with the USFDA this month.
This French biotech company has described the new drug as a “multi-hundred million” dollar opportunity. Lutathera has the potential to transform AAA’s fortunes.
Buono’s AAA, which was spun off from Europe’s physics research centre CERN 15 years ago, had sales from existing diagnostic products of US$ 34.9 million in the first quarter of 2017. Lutathera is unusual in harnessing the same molecule that is already used to diagnose cancer to also deliver treatment.
After Celgene, Cardinal Health pulls out of China due to regulatory concerns
After Celgene
decided to reduce its footprint in China earlier this month, in order to
support only its clinical development and regulatory affairs activities in the
country, this week we heard about US drug distributor Cardinal Health putting its
China business on the block.
As per news reports, state-backed Chinese pharma companies
have evinced interest in a deal that may be worth up to US$ 1.5 billion. Shanghai Pharmaceutical, China Resources Pharmaceutical, and Sinopharm are
among those evincing interest in buying Cardinal Health, one of China’s largest drug distributors.
Ohio-based Cardinal wants to exit the country due to concerns around China's upcoming drug distribution reform, which is likely to slow down its growth. Cardinal has also been diversifying — in April it announced a US$ 6.1 billion deal for Medtronic Plc’s medical supplies units.
It has reportedly hired Lazard as an adviser for the China sale and the first
round of bidding is due later this week.Meanwhile, Celgene is offloading its Chinese operations to
the biopharmaceutical major Beigene. It is also giving Beigene the rights to Abraxane, Revlimid and Vidaza in China. This way, Beigene will assume responsibility for making and selling the approved drugs, along with Celgene’s pipeline prospect CC-122 in China. Celgene had also announced that it would buy a stake in BeiGene to help
develop and commercialize the China-based cancer immunotherapy developer's
treatment for solid tumor cancers, expanding its position in the field of
immuno-oncology. When the deal closes in the third quarter of this year,
Beigene will instantly become a commercial-stage biotech.
Impressions: 2909
https://www.pharmacompass.com/radio-compass-blog/gsk-s-overhaul-begins-under-new-ceo-sandoz-loses-us-940-million-lawsuit
#PharmaFlow by PHARMACOMPASS
27 Jul 2017
This week in our compliance round up, we look at the continuing problems at Pfizer’s McPherson unit in the US and China FDA’s entry into the ICH as a regulatory member. Yet again, WHO sources API from a plant in China, where USFDA had raised data integrity concerns. Meanwhile, Aurobindo Pharma’s Unit VII clears FDA inspection with zero observations.
Problems continue at Pfizer’s US facility; its sure-shot biosimilar gets rejected
Earlier this year,
Pfizer’s fill/finish manufacturing facility in McPherson, Kansas, received a warning letter from the US Food and Drug Administration (USFDA). The compliance concern was initially revealed in a press release issued by Momenta Pharmaceuticals — a biotechnology company developing a generic version of Teva’s long-acting Copaxone® 40mg/mL (glatiramer acetate injection). Momenta is working in
collaboration with Sandoz, which in turn has tied up with Pfizer as its fill/finish
manufacturing partner.
This week, a month after the FDA staff found that Pfizer’s biosimilar of Amgen’s drug Epogen (epoetin alfa) was nearly identical and an FDA advisory committee followed to recommend approval with a 14-1 vote, the FDA issued a complete response letter (CRL) to Pfizer.
The letter cited
concerns which had already been raised in the warning letter issued on February 14, 2017, following a
routine inspection of the facility.
This development
continues to be positive news for Teva, as Copaxone generated US$ 4.22 billion in sales last year. Continued
compliance concerns at Pfizer indicate that Momenta will still have to wait for
its generic to get approved.
While
previous FDA inspections at the McPherson facility had raised concerns over the assurance of product sterility, no warning letter had ever been issued to this site.
In
February 2015, Pfizer acquired the McPherson site through its US$ 17 billion acquisition of Hospira. Pfizer was aware of Hospira's manufacturing record
when it struck the deal, as the company was issued FDA warning letters in four of the seven continents — Europe, North America, Asia and Australia.
Once again, WHO sources API from Chinese firm where FDA had
raised concerns
Three
weeks after PharmaCompass shared the differences in assessments of the World Health Organization (WHO) and the USFDA over
the observations at a Mylan finished formulation
site in India, a similar situation has arisen at an active pharmaceutical
ingredient (API) facility in China.
An
inspection conducted by the USFDA at Qinhuangdao Zizhu Pharmaceutical from November 28 to December 1, 2016 uncovered significant data
integrity concerns and failures in the level of adherence to cGMP (current good
manufacturing practices) for APIs.
In
the warning letter issued to the firm, the laboratory analysts admitted to FDA inspectors that they had been “setting the clock back and repeating analyses for undocumented reasons.”
At Qinhuangdao Zizhu, “initial sample results were overwritten or deleted” and the company “reported only the passing results from repeat analyses”.
In addition to not having effective measures to control data within their computerized systems, the FDA investigators found that the firm “relied on incomplete information” to determine whether Qinhuangdao Zizhu’s drugs met established specifications.
The investigators found “a recurring practice of re-testing samples until acceptable results were obtained” and that batch production records “contained blank or partially completed manufacturing data”.
On
March 8, 2017, Qinhuangdao Zizhu Pharmaceutical was placed on the import alert by the USFDA.
Almost
a year prior to the USFDA inspection, in October 2015, the company had been
inspected by a WHO Prequalification Team (PQT) for levonorgestrel, mifepristone and ethinylestradiol APIs. The inspection concluded with “five major deficiencies including data integrity issues and several minor deficiencies”.
The
WHO went ahead and closed their inspection as compliant based on corrective and
preventive actions (CAPAs) provided by the manufacturer.
In
view of the USFDA actions, and the fact that Qinhuangdao Zizhu Pharmaceutical
is the only WHO-PQT prequalified source of levonorgestrel API, as in the case of Mylan, the WHO approach towards the compliance position has been
to focus extensively on product quality.
The WHO has requested manufacturers that use levonorgestrel manufactured by Qinhuangdao Zizhu to take “additional measures such as comprehensive testing upon receipt” to help ensure that the quality of all batches of levonorgestrel is assured.
In
addition, the WHO has said that procurement agencies may continue to procure
FPPs that contain API produced at Qinhuangdao Zizhu Pharmaceutical, until
further notice.
The WHO-PQT is planning to conduct an on-site inspection of
Qinhuangdao Zizhu Pharmaceutical and also plans to work with finished
pharmaceutical products manufacturers to identify additional sources for
levonorgestrel.
China
FDA approved as an ICH member
In a major boost to China’s pharmaceutical growth plans, the International Council for Harmonization (ICH) Assembly approved the China Food and Drug Administration
(CFDA) as a new Regulatory Member. This decision was taken during a meet in
Montreal, Canada, from May 31 to June 1, 2017.
While compliance concerns linger over some pharmaceutical factories in the country, China’s acceptance of this membership indicates that the country is prepared to bring its drug manufacturing and testing practices in line with international quality standards.
ICH was created in
1990 to bring regulatory authorities and the pharmaceutical industry together
in order to discuss scientific and technical aspects of drug registration. Over
the last 25 years, ICH has worked on achieving greater global harmonization so
that safe and effective drugs are developed and registered in the most
resource-efficient manner.
In India, Aurobindo’s Unit VII gets zero observations; Lupin founder passes away
Indian pharmaceutical industry lost a
veteran this week. Desh Bandhu Gupta, the founder chairman of Lupin and a self-made billionaire, died in Mumbai at the age of 79.
Five years back, he had handed over the reins of Lupin to his eldest daughter Vinita
Gupta and son Nilesh Gupta.
Desh Bandhu Gupta, or DBG as he was
known, was a deft businessman who founded Lupin in 1968 with just Rs 5,000
borrowed from his wife. Prior to this, he was the professor of chemistry at the
Birla Institute of Technology and Science, Pilani. He went on to become India’s 20th richest person with an estimated net worth of US$ 5.1 billion (according to the 2016 Forbes India Rich List).
While much of the industry abandoned making anti-TB drugs, given the low margins and the government's price controls, Lupin remained consistent as the world’s largest supplier of anti-TB drugs. DBG forged global alliances to develop new medicines to fight tuberculosis.
Meanwhile, another Indian company — Aurobindo Pharma — sailed through a USFDA inspection with zero observation. Aurobindo Pharma’s Unit VII is a formulations manufacturing facility and one of the
largest facilities for the company from which has filed the maximum ANDA
applications to the FDA.
According to a recent company presentation to investors, the company has filed 158 ANDAs (abbreviated new drug application) from this facility, of which 88 drugs received final approvals and 20 drugs have tentative approvals and 50 are currently under review.
Impressions: 4004
https://www.pharmacompass.com/radio-compass-blog/fda-problems-at-pfizer-s-us-facility-continue-china-fda-joins-ich
#PharmaFlow by PHARMACOMPASS
29 Jun 2017
This
week, Phispers brings you a short analysis on how FDA might be promoting
European drugmakers over others. There is also news on how India plans to set
up a drug audit office in China to check quality of APIs coming from there.
Besides, there is news on lawsuits against J&J, a report on drug spends in
the US and updates on new drug trials and approvals.
Does
the FDA promote European manufacturers over others?
Does
the US regulator have more faith on European manufacturers over those based in
India and China? Recent news reports seem to suggest it does.
Thomas Cosgrove, the Director of the Office of Manufacturing Quality (OMQ) within US Food and Drug Administration’s Center for Drug Evaluation and Research (CDER) spoke at the Food and Drug Law Institute's annual conference last week. Cosgrove directs CDER’s compliance activities with respect to current good manufacturing practice (cGMP) and product quality.
In
the coverage provided by RAPS, Cosgrove detailed some of the biggest challenges drugmakers face when contracting with foreign manufacturers. “If any firm in the supply chain falls down, the supply chain itself can fall down. This is a very real risk," Cosgrove said, noting that the agency can reject applications for drugs over good manufacturing practice (GMP) issues.
He further said: “You're pretty confident that those European companies you're dealing with have a strong culture of quality and can perform pretty consistently," But, like in other parts of the world, these companies might not have a deep experience with how the US regulations work or even how to deal with the FDA, and may not have been inspected by the agency before, he added.
Cosgrove’s comments come at a time when a compilation by Barbara Unger on FDAZilla.com highlighted that the warning letters issued
due to data-integrity concerns to firms in US and Europe (13 total) were more
than those issued to firms in India (9) and almost equivalent to firms in China
(14).
There
have also been other examples where inspection data highlights a difference in
inspection outcomes for the same facilities. PharmaCompass had recently covered the US and EU’s efforts to utilize each other’s GMP inspections, and how such a dependence maybe problematic.
While
FDA has stepped up its inspections of foreign drug manufacturers in recent
years, there are more than 1,000 foreign drug facilities the agency has never
inspected.
India
to restart inspection of Chinese API manufacturers
India
is cracking the whip on quality and will restart inspecting drug manufacturing facilities in China soon, in order to ensure only quality
active pharmaceutical ingredients (API) are imported from countries like China.
“In the light of the fact that India has faced repeated scrutiny of its manufacturing facilities in the name of quality medicines, the commerce ministry along with other concerned ministries are serious to set up a permanent audit office in China to conduct inspections on a regular basis in China,” G N Singh, Drug Controller General of India, said.
The
plan to set up a drug audit office in China for inspecting manufacturing units
there is not new. It has been in the pipeline for the past three years, as the
project is awaiting approval from several ministries in both India and China.
India’s health ministry is also in the final stages to release a draft guideline towards enhancement of GMP to align India-specific standards with global regulations for better product quality of pharmaceutical products.
The ice-bucket challenge
winner! First new treatment approved by the FDA for ALS in 22 years
Last
week, the US FDA approved Radicava (edaravone)
— a drug to treat patients with the rare amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease.
ALS is a progressive disease that attacks and kills the nerve cells that control voluntary muscles. Eventually, the brain’s ability to start and control voluntary movement is lost, and the patient succumbs to the disease — usually after three to five years from the onset of the symptoms.
Around
12,000-15,000 Americans are said to have ALS. Most people with ALS die from
respiratory failure. British physicist Stephen Hawking is suffering from ALS.
An “ice bucket challenge” conducted in 2014 drew global attention back to ALS. The challenge involved people pouring ice-cold water over each other’s heads, and posting a video on social media, seeking funds for research on the condition.
Edaravone
is an intravenous drug. The drug is being sold in Japan and South Korea by Mitsubishi Tanabe Pharma Corp.
The company is selling the drug at US$ 145,000 per year.
In
the US, the last drug approved to treat this disease was Riluzole in 1995. However, the drug isn’t a cure for ALS, it only delayed the need for a breathing tube. Six months of treatment with edaravone reportedly reduced the rate of functional decline in patients by about a third.
Another
bad week for Teva — its new MS drug fails to meet primary endpoint
Teva’s bad days don’t seem to relent. Last week, it’s late-stage
trial for laquinimod — considered a successor to the aging flagship multiple sclerosis therapy Copaxone — failed the test on the relapsing-remitting form of the disease.
The
drug did not meet the primary endpoint, trying to significantly improve the
time to disability progression compared to placebo after three months.
Teva’s laquinimod was heralded as its brightest pipeline prospect. Investigators are still testing this drug for primary progressive MS and Huntington’s disease. But due to this failure, it’s unlikely that analysts will ascribe much potential value to the drug.
Early last year, Teva (which had partnered with Active
Biotech) was forced to suspend use of
the highest dose of laquinimod due to cardio side effects. Despite this
setback, Teva was hopeful of a win with the lower doses and was preparing for a
launch after completing studies this year.
Trump
administration gets FDA to switch TVs from CNN to Fox News
The
Trump administration is ensuring researchers at FDA view the media of its
choice. This week, CBS News confirmed an email was sent to researchers at the
FDA's Center for Biologics Evaluation and Research to change the channel on
internal television screens from CNN to Fox News.
CNN and Donald Trump have been feuding for several months now. On May 2, CNN had refused to air an advertisement issued on 100 days of Trump administration, that called mainstream media “fake news” — a term frequently used by the president.
The email from “[White Oak] Digital Display” sent on Wednesday, May 3, was sent to inform the researchers of the “reason for the change from CNN to Fox". White Oak is the name of the FDA’s campus.
The email informs employees that the decision came from the Trump administration. “The reason for the change is that a decision from the current administration, administrative officials has requested that all monitors, under our control, on the White Oak Campus, display FOX news,” the email reads.
People
are paying less for drugs, says IMS
Quintiles report
While there
is widespread outrage in the US over soaring drug prices, a new study by
QuintilesIMS Institute shows people are, on an average, actually paying less for their medications than they did a
few years ago.
QuintilesIMS Institute is a research organization that specializes in
healthcare analysis. The report is independent, and did not receive
industry funding.
While drug prices are on the rise with net prices rising 3.5 percent last year, patients’ out-of-pocket costs for medicines have declined — from US$ 32 per name-brand prescription in 2013 to US$ 28 today, the study said.
“The outlook for medicine spending through 2020 is for mid-single digit growth driven by further clusters of innovative treatments, offset by a rising impact from brands facing generic or biosimilar competition,” says a QuintilesIMS report titled ‘Medicines Use and Spending in the U.S. – A Review of 2015 and Outlook to 2020’.
However, this isn’t the only report that shows this counterintuitive pattern of declining out-of-pocket costs. A Peterson-Kaiser Health System Tracker report last year found a slight decline in patients' personal spending on prescriptions, even as the overall costs increased.
Mixed
week for J&J, as it loses talc verdict and wins Xarelto case
Last week was a mixed week for Johnson & Johnson (J&J). On the one hand, the St. Louis jury
ordered Johnson & Johnson to pay US$ 110 million to Lois Slemp, a lady who claimed several decades of using talc products caused her ovarian cancer that later spread to her liver. On
the other hand, J&J won a bellwether case last week over the alleged risks
of its blockbuster drug, Xarelto.
The Slemp trial lasted several weeks and had Slemp’s attorneys call upon scientists to testify studies documenting a link between ovarian cancer and talc use.
Slemp’s attorneys also presented documents showing that J&J knew about the risks. J&J, however, said it will appeal against the verdict.
A company spokesperson said a previous victory (for J&J) in St. Louis and two in New Jersey “highlight the lack of credible scientific evidence behind plaintiffs’ allegations."
In the other case, a US court (the federal jury
in New Orleans) cleared Bayer AG and J&J of liability in the first trial emanating from thousands of lawsuits that blamed
injuries on the blood thinner Xarelto.
“The jury's verdict affirms both the safety and efficacy of Xarelto, and that its FDA-approved label contains accurate, science-based information on the benefits and risks of this life-saving medicine,” Bayer said in a statement.
Rivaroxaban's total 2016 sales were $ 5.392 billion.
Impressions: 3209
https://www.pharmacompass.com/radio-compass-blog/does-the-fda-promote-european-manufacturers-over-others-the-ice-bucket-challenge-winner
#PharmaFlow by PHARMACOMPASS
11 May 2017
Within two
months of 2017, we have already seen several pharmaceutical companies come
under the regulatory lens and face action.
This week, PharmaCompass
does a compliance recap, wherein companies like Pfizer saw lapses in their current good
manufacturing practices (cGMPs) and companies in India, like Dr. Reddy’s and Cadila Healthcare, who received warning letters in the
past, were busy with regulatory re-inspections at the erring sites.
Pfizer’s US facility receives a warning letter from the FDA
Pfizer’s fill/finish manufacturing facility in the United States recently received a warning letter from the US Food and Drug Administration (USFDA). This information was revealed in a press release
issued by Momenta Pharmaceuticals a
biotechnology company developing a generic version of Teva’s long-acting Copaxone® 40mg/mL (glatiramer acetate injection).
Momenta’s Glatopa 20 mg/mL product is already
available in the US market and is promoted by Sandoz, which in turn has contracted the fill/finish manufacturing operation to Pfizer’s facility in McPherson, Kansas.
In February 2015, Pfizer
acquired the McPherson site through its US $17 billion acquisition
of Hospira. Pfizer was aware of Hospira's manufacturing record when it struck
the deal to buy the drugmaker as the company was issued FDA warning letters on four of the seven continents
Europe, North America, Asia and Australia.
While previous FDA inspections
at the McPherson facility had raised concerns over the assurance of product
sterility, no warning letter had ever been issued to this site.
This has been the first
positive news for Teva this year, after a series of setbacks. Copaxone
had generated US $ 4.22 billion in sales
last year.
And as per Momenta’s press statement, “Glatopa 40 mg ANDA (abbreviated new drug application) remains under regulatory review.” While Momenta says it is working with Sandoz to resolve the matter, it is of the view that “an approval in the first quarter of 2017 is unlikely.”
“Pfizer has indicated that the warning letter does not restrict the production or shipment of the Glatopa 20 mg (glatiramer acetate injection) product,” Momenta stated in its press release.
The Pfizer warning letter
will also be welcome news for Mylan as it had recently won a court ruling where four Orange Book-listed patents relating to Copaxone® 40 mg/mL were invalidated based on obviousness. Mylan has “filed a substantially complete ANDA” for a three times per week Glatiramer Acetate Injection 40 mg/mL.
Baxter’s cGMP deficiencies result in US$ 18 million settlement
Last
month, Baxter International and Baxter Healthcare Corporation settled a type of civil lawsuit that
whistleblowers are known to bring. It was settled under the False Claims Act
(FCA) case with the Department of Justice (DOJ) for US$ 18 million.
The
settlement in which there was
neither an admission of liability by Baxter nor a concession by the United States that its claims are not well founded was an outcome of the government alleging that Baxter submitted false claims for a drug sold to the Department of Veterans Affairs and Department of Defense, as well as reimbursed by the Medicare and Medicaid programs, because the drug was “adulterated.”
A detailed blog written by Stephanie Trunk and Emily M. Leongini
highlights that the issue emanated from the “presence of visible mold on HEPA filters installed above the clean rooms” where Baxter manufactured sterile intravenous (IV) solutions. The managers at Baxter prevented the relator and others from removing the moldy filters and from cleaning or sanitizing other associated contaminated surfaces, says the complaint.
This
handling of the moldy filters by Baxter allegedly violated numerous cGMP
requirements set forth in the FDA regulations. This includes the requirement
that a manufacturer establish, and also follow, its own internal standard
operating procedures.
While the government acknowledged that there was no evidence to suggest that Baxter’s IV solutions had been impacted by the moldy filters, it alleged that the IV solutions violated the FCA because of “Baxter’s failure to comply with cGMP requirements.”
In
the past, cGMP violations have had the DOJ collect US$ 750 million from a GSK subsidiary in 2010 and US$ 500
million from Ranbaxy in India in 2013. With an increasing trend of warning letters being issued by the FDA to pharmaceutical manufacturers, it remains to be seen if DOJ will further “highlight the materiality of cGMP compliance to product purchases in support of FCA claims”.
Zydus turns around compliance problems with a zero 483 inspection
Zydus’ Moraiya (Gujarat, India) facility accounted for 60 percent of Cadila’s revenues
in the US, its largest market. In an inspection performed by the FDA in
September 2014, the investigators found that in 2013, Cadila had failed to
adequately review 106 consumer complaints (out of 106 complaints received) and
in 2014, up to the date of the inspection, they failed to adequately review
another 132 consumer complaints (out of 132 complaints received).
While at the time of the
inspection, Cadila had already taken the decision to recall products like Warfarin 2 mg (due to oversized tablets), Promethazine 25 mg (due to mixed tablets in the
same bottle) and Atenolol 25 mg (due to “thicker appearance”), the inspectors got “no assurance” that the quality system at Cadila was under control and stated that the “deficiency appears to be a pattern of problem” at the Cadila site.
Zydus
received a warning letter from the FDA in December 2015. Last week, Zydus announced
that it did not receive any observations from the USFDA for its formulation facility at Moraiya,
which indicates a successful resolution of the compliance at the plant.
The
company said that the USFDA inspected the plant from February 6 to 15.
What’s next at Dr. Reddy’s and Marksans in India?
Marksans Pharma, a company with a questionable compliance track record, saw its manufacturing facility in Goa (India) fail an inspection by the UK drug regulator last year. The inspectors noted critical data integrity violations which included “evidence of destruction of multiple parts of records of prime data”.
In
a filing with the Bombay Stock Exchange (BSE), the company announced that its plant in Goa had an inspection by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) from February 14-17, 2017. The inspection was completed without any critical observations, the company informed. It is now awaiting further instruction from the agency in this regard.
In a similar announcement, Dr. Reddy’s informed the bourses that its Miryalaguda facility has been issued a Form 483 by the USFDA with three observations, which the company is addressing. The audit of the company’s API manufacturing plant at Miryalaguda by the USFDA was completed on February 21, 2017.
Back
in November 2015, the same facility had received
a warning letter after FDA inspectors found partially-filled documents in the garbage.
Our view
Over
the past years, we have seen compliance concerns being raised time and again at
pharmaceutical manufacturing operations. Last week, Sato Pharmaceutical, a
company established in 1939 in Japan, received a warning letter from the FDA as it
failed to establish an adequate system for monitoring the conditions of its
cleanroom environments.
Prior to that, FDA’s April 2016 inspection of ACS Dobfar’s operations in Brazil Antibioticos do Brasil (ABL)
led to the issuance of a warning letter after
the FDA investigators found that the filling zone for sterile injectable
product was not sufficiently robust.
While
data integrity concerns dominated news headlines last year, it seems that
aseptic fill/finish may become a leading cause of concern with regulators.
It’s clear that manufacturing can no longer be taken for granted as companies of all sizes are suffering economically from their inability to comply with good manufacturing practices.
Impressions: 7176
https://www.pharmacompass.com/radio-compass-blog/pfizer-s-us-facility-receives-a-warning-letter-as-baxter-s-cgmp-deficiencies-result-in-multi-million-dollar-legal-settlement
#PharmaFlow by PHARMACOMPASS
23 Feb 2017
This week, Phispers highlights more bad news for Israeli drugmaker Teva, along with news on the ‘overwhelming efficacy’ of blood thinner Rivaroxaban over Aspirin, Sanofi’s plans to resubmit its application for Sarilumab, Denmark’s entry into the tug of war for hosting the EMA headquarters and are routine round up of global non-compliance concerns.
Teva CEO steps down, as
another bribery probe emerges and discussions of a split start
The chief executive of Teva Pharmaceutical Industries, Erez Vigodman, stepped down after serving for
three years. He has been replaced by Chairman Yitzhak Peterburg for the interim period. Teva is the world's biggest maker of generic
drugs.
In the last five years, he is the third CEO to vacate the position. A sudden change in the company’s leadership came just two months after the resignation of Sigurdur Olafsson, the former head of Teva’s main business unit — generic medicines. Both the executives played an important role in Teva’s US $ 40.5 billion purchase of Actavis Generics last year, touting it as a move that would provide growth.
Instead, the acquisition led to more bad news.
In a short statement after leaving, Vigodman stated: “I believe that now is the right time for me to step down. It has been a privilege to lead Teva, and I am proud of all we have accomplished. I am confident that the company’s future is bright.”
A lot of bad news has already piled up for Teva’s investors since the New Year. This includes the following negative events:
The market is criticizing Teva’s acquisition of Actavis (Allergan’s generics division) for US $ 40 billion in cash and shares.
Teva’s acquisition of Mexican company Rimsa proved to be a catastrophe. Rimsa's plants are now shut down.
Apart from the bad decisions over acquisitions,
Teva is also involved in two legal wrangles. One was a case of bribery in
developing countries, in which Teva agreed to pay US $ 519 million to US
authorities after paying bribes to officials in Mexico, Ukraine and Russia to
boost sales. Another legal issue
involves the investigation of Teva over bribe allegations by Israeli
authorities which came up a day after Vigodman stepped down.
A US district court ruling invalidated four patents out of five on its top seller — the multiple sclerosis drug Copaxone. The ruling, issued in late January, may open the door to generic
competition (Novartis and Mylan) for thr drug that generates a fifth of Teva’s US $ 20 billion in annual sales.
In the company’s own words: “New products stemming from that asset (Copaxone) would be unexpectedly delayed, while prices of its copycat medicines are likely to remain under pressure in the US, prompting a cut to its 2017 profit forecast.”
Following the resignation, at the company's earnings call
earlier this week, analysts started asking if Teva would consider a split-up?
FDA issues Warning Letters to
Indian, Japanese & Chinese firms
Sato
Pharmaceutical, a company established in 1939 in Japan, received a warning letter from the FDA as it failed to establish an adequate system for monitoring the conditions of its cleanroom environments. Following the inspection, the firm revised its standard operating procedure related to the “Aseptic Production Area”, however,
the FDA found the response to be deficient.
FDA inspectors also uncovered that the company had not
performed the necessary smoke studies to evaluate air flow characteristics of
its open Restricted Access Barrier System (RABS). The company released sterile
products manufactured on the aseptic processing line, without studies to
demonstrate unidirectional airflow over the exposed sterile product during
processing.
Although, Sato renovated its RABS to use a closed design and
conducted validation studies, the response was found deficient as it does not
address the quality of the products which had already been released
to the U.S. market using the original open RABS design.
An active
pharmaceutical ingredient (API) manufacturer in India, Resonance Laboratories Private Limited also
received a warning letter from the FDA as the inspectors
raised concerns over the facilities water systems and cleaning validation
methods.
The FDA found that the firm’s response to the inspection observations had failed to perform a retrospective review of CGMP deficiencies on the quality of the products which had already been distributed within the United States.
PharmaCompass
had shared the news about the compliance troubles at
Resonance in November, 2016.
The FDA also issued warning letters this week to two Chinese firms who
had been placed on its Import Alert list last year. The warning letters sent to
Ausmetics Daily
Chemicals (Guangzhou) Co., Ltd. and Zhejiang Bangli Medical Products Co., Ltd.
showed that the companies failed to sufficiently test the batches of the final
product they produced and did not adequately confirm the quality of the
incoming active raw materials.
Bayer’s Rivaroxaban shows 'overwhelming efficacy' over aspirin
Back in 1897, a young scientist at a Bayer laboratory in Wuppertal, Germany — Dr. Felix Hoffmann — synthesized a chemically pure and stable form of acetylsalicylic acid (ASA), which
became the active ingredient in Aspirin™.
Since then, Aspirin has been an important medicine due to its
remarkable pain relief, as well as cardiovascular (CV) event prevention
properties. The medicine has truly stood the test of time.
Last week, Bayer AG and its development partner Janssen Research & Development announced the successful outcome of a
large-scale Phase 3 study -- COMPASS, involving 27,402 patients, that assessed the
effect of blood thinner Xarelto (rivaroxaban)
in preventing major adverse cardiac events (MACE).
The trial was scheduled to finish next year but
was stopped early on the advice of an independent Data Monitoring Committee, after the primary endpoint of prevention of MACE — which includes cardiovascular death, myocardial infarction and stroke —reached its pre-specified criteria for superiority over aspirin.
The drug could potentially be used on 30 million
patients with coronary artery disease (CAD) and peripheral artery disease (PAD), in addition to the roughly 25 million patients
it sees in the atrial fibrillation market, says Bayer.
Xarelto is currently the only non-vitamin K
antagonist oral anticoagulant (NOAC) currently under assessment in this
high-risk patient population. The drug is already on the market for reducing the risk of stroke and blood clots.
Sanofi fixes problems
in French plant, to resubmit application for Sarilumab
In 2014 and 2015, while reviewing new drug
applications, the US Food and Drug Administration (FDA) had raised manufacturing questions in only one Complete Response Letter (CRL) sent to the applicant. However, by mid-December, 2016 “an astonishing 40 percent were specifically tied to questions the agency raised about the manufacturing capabilities of a drugmaker or its contractor.”
Manufacturing issues derailed sales forecasts through new drug
approvals of Sanofi, AstraZeneca, Valeant, Bristol-Myers Squibb, Pfizer and many others.
In October 2016, Sanofi received the FDA’s Form 483 for it’s Le Trait facility in France since manufacturing deficiencies were
discovered during a routine good manufacturing practice (cGMP) inspection where
Sarilumab and Dupilumab are manufactured.
This plant is involved in one of the last steps in the manufacturing process of Sarilumab — an investigational interleukin-6 receptor (IL-6R) antibody for the treatment of adult patients with moderate to severely active rheumatoid arthritis (RA) which is a combined program of Sanofi and Regeneron. Due to the manufacturing issues, FDA issued a CRL regarding
the Biologics License Applications (BLA) for Sarilumab.
Sarilumab is said to become a blockbuster after beating the world’s best-selling drug AbbVie's Humira (adalimumab) in a head-to-head trial. Analysts have previously
predicted the drug could bring in more than US $ 1 billion by 2020.
In response to the letter received from the FDA, the French company has filed a comprehensive corrective action plan with the FDA and is “working towards a timely resolution that addresses these concerns.” Once the issues are addressed, both companies said they intend to seek a way to bring the drug to market.
In January 2017, Sanofi and its drug development partner Regeneron Pharmaceuticals said they have resolved manufacturing defects at Le Trait facility, which caused the delay for the approval of Sarilumab drug. Sanofi’s CEO Olivier Brandicourt said: “We worked closely with the US FDA to implement a corrective plan and got positive feedback".
Assuming the formal inspection will also play out
positively, the companies have decided to resubmit their application for
Sarilumab by the end of March.
Denmark
officially bids for relocation of EMA head office
The future location of the European Medicines Agency (EMA) — one of the regulatory jewels of the EU — has been a consistent topic of conversation since the outcome of the Brexit vote.
The intervention of the Japanese government in
early September 2016 brought the EMA issue further into the open when a 15-page letter came up where Japanese officials told their counterparts in the UK that if “the EMA were to transfer to other EU Member States, the appeal of London as an environment for the development of pharmaceuticals would be lost, which could possibly lead to a shift in the flow of R&D funds and personnel to Continental Europe.”
And now, Denmark is also in the list of countries that are bidding for EMA headquarters’ relocation. Copenhagen’s candidacy launch on February 8 comes in the wake of similar launches by
Amsterdam, Milan, Stockholm, Barcelona and Dublin. Only the Czech Republic and
Estonia have ruled themselves out, according to the Financial Times.
Therefore, we may see a 20-way tug of war amongst cities that want to host the EMA.
The Danish Medicines Agency is excited about the Danish government’s decision. Thomas Senderovitz, Director General of the Danish Medicines Agency, said: “The EMA is the most important European coordination forum in the pharmaceutical field, and Copenhagen offers a visionary and innovative life science cluster. Major international pharmaceutical companies have a presence in Copenhagen, and we offer a strong administration and unique culture for collaboration between the health sector and universities in Denmark and southern Sweden”. As the news came out, healthcare giant Novo Nordisk backed and supported the decision of the Danish Government.
India’s Strides plans to spin off API unit
Just two months after Perrigo agreed to sell its entire shareholding in Perrigo API India to Strides for INR 1000 million (US $14.8
million), Strides announced an organizational restructuring plan. As per the
plan, Strides has decided to move away from its business-to-business (B2B) model to a business-to-consumer (B2C) model, which
includes de-merging and listing its APIs business, exiting
probiotics and capping its investment in the biotech business which was also
approved by SeQuent Scientific, which bought into Shasun several years ago.
SeQuent also has a veterinary drug business. Strides Shasun plans to rename itself as Strides Pharma. Post restructuring, the new
Strides Pharma will comprise its retained formulations business having four US
FDA-approved plants in India, Europe and Singapore, and three research and
development (R&D) centers. This business will have a front-end presence in
the regulated markets of Australia, US and the UK and emerging markets of
Africa and India.
Last year, Strides Shasun had mentioned they plan to hive off its commodity focused API manufacturing unit as a separate business. Strides — with two API manufacturing facilities, one in India and one in the UK — is a global supplier of painkiller (Ibuprofen), anti-epileptic medication (Gabapentin) and anti-acidity medication (Ranitidine). Strides had said that it would retain API capacities required for
captive use while setting up a separate company for manufacturing low-margin APIs such as Ibuprofen, Gabapentin and Ranitidine.
Impressions: 5515
https://www.pharmacompass.com/radio-compass-blog/teva-ceo-steps-down-fda-warning-letters-to-firms-in-japan-india-china
#PharmaFlow by PHARMACOMPASS
16 Feb 2017
This week, Phispers has lots on generics. While the global leader Teva has more troubles at hand, generic players in the US face fresh lawsuits, and Sanofi plans to sell its European generic unit. There is also talk of Novartis buying America’s generic-drugs maker Amneal. In other news, oncologists find problem with clinical trials, and China shuts plants to curb pollution
Teva braces declining sales, lawsuits
and closure of its Mexico plant
There is more bad news from Israel’s Teva Pharmaceutical Industries. First, its Rimsa plant in Mexico is said to be shut, and a lot of employees have been (reportedly) laid off. As per a news report, it’s difficult to make the Rimsa
plant operational anytime soon.
Teva had invested US $ 2.3 billion in the facility. There are reports that the company may
make a write-down on its investment in Rimsa. In September, the global leader
in generics had claimed that the Espinosa brothers, who had controlled Rimsa
until its sale to Teva, had deceived the regulatory authorities and patients
for years and sold defective and illegal drugs.
Teva’s troubles don’t end there. The company is also setting aside US $ 520 million in its bid to settle allegations of paying bribes in Russia, Mexico and Ukraine. In its latest earnings report released Tuesday, Teva noted that “advanced discussions” are under way with the federal courts in the US to resolve the incidents, which took place between 2007 and 2013.
Teva has
completed 12 acquisitions worth US $ 46 billion in the last four years. Teva’s blockbuster Copaxone,
which brings in 19 percent of its overall sales, has lost several patent
challenges in the US and is likely to face generic competition early next year,
putting more than US $ 4 billion in sales at risk. Even without a generic
competitor, sales declined 2.2 percent year-on-year in the third quarter this
year.
To control
pollution, north China industrial hub curbs drug production
If you live in Delhi, and are coping with the hazardous pollution levels, here’s something that will interest you. A wide-ranging ban has
been imposed in a northern Chinese industrial hub on production at drug plants,
steel mills and other businesses.
This is a
last-ditch attempt by the government of Shijiazhuang city to meet this year’s pollution control target — to reduce the levels of PM 2.5 (fine particles that pose a risk to human health) by 10 percent. Shijiazhuang is the capital of the northern Hebei province, which reported economic growth of 6.8 percent in the first three quarters of this year.
Last week,
the government of Shijiazhuang city said for the remaining 45 days of the year,
it will curb output at thermal power plants, halt all production at industries
such as steel and cement, and limit manufacturing of pharmaceuticals, chemicals
and even furniture.
In 2014,
President Xi Jinping had responded to public outrage over high smog levels. As
a result, local officials are trying hard to strike a balance between pollution
control and economic growth.
Shijiazhuang
is home to major active pharmaceutical ingredient (API) producers such as North China Pharmaceutical, CSPC Zhongnuo Pharmaceutical, CSPC Ouyi Pharmaceutical and many others. These companies are critical to the
global antibiotic supply chain as they provide the building blocks for
antibiotic manufacturing, such as 6-APA and 7-ACA, along with commonly used
antibiotics such as Penicillin, Amoxicillin, Amipicillin and Azithromycin.
PharmaCompass has been routinely
covering the Chinese bulk drug industry and its impact on the environment. In April this year, PharmaCompass
had reported how school children in China were wearing gas masks due to pollution concerns. And prior to that, we had
carried an article on how dependent the world has become on bulk drugs from China.
More trouble
for generic drug-makers in the US as unions file lawsuits
In a fresh
salvo at the generic drug industry, a union representing sergeants of the New
York Police Department is attempting to hit some companies with civil penalties. The generic industry is already facing charges from a
two-year US Justice Department antitrust probe.
The union
has filed two lawsuits against two groups of drug-makers, which includes Novartis AG’s generic drug unit, Ireland-based Perrigo Co., India’s Wockhardt and Taro Pharmaceutical Industries (Israeli subsidiary of India’s Sun Pharma). The union has alleged that the companies colluded to
raise prices of two dermatological creams by as much as 1,000 percent since
2013.
Besides
this, at least four other unions
have filed lawsuits of their own, with two of them adding Actavis Inc., acquired in August by Teva, to the list of
defendants. All the unions manage health benefits for their members. The
unions say they overpaid for the drugs due to the price collusion. They point
to data that the drug-makers took price hikes on certain medicines by nearly
the same amounts within months of each other.
A lawyer for
the New York sergeants’ union said he expects a judge will call a conference in December
to decide if the cases can be combined.
Novartis may
buy generic drug-maker Amneal for US $ 8 billion
Swiss
healthcare major Novartis AG is in talks to acquire American generic-drugs maker Amneal Pharmaceuticals. Through this acquisition, Novartis plans to strengthen
its Sandoz
business. According to Bloomberg, Novartis and Amneal may reach an agreement soon. Amneal
makes the antiviral acyclovir (to treat herpes) and gabapentin (for epilepsy and pain). The
acquisition could cost Novartis around US $ 8 billion. Amneal is a family-owned
business led by co-founders Chintu and Chirag Patel and has operations in North
America, Australia, Europe and Asia. Its portfolio of generic treatments
includes around 115 approved molecules in the US.
Sanofi to
sell off European generic drug unit
French drug
maker Sanofi
confirmed it has decided to sell off its generic drug unit in Europe. The decision will affect two
manufacturing plants in the Czech Republic and Romania.
Sanofi CEO Olivier Brandicourt recently informed investors that the company has “made a definitive decision to initiate a carve-out process and divest the generics portfolio in Europe.” The move is part of the company’s 2020 strategic roadmap. He, however, did not provide details.
Sanofi had
acquired Zentiva, a Czech generic business, in 2008 for US $ 2.6 billion. And Sanofi’s generic business is centered around this acquisition. The business is particularly strong in the Czech Republic, Romania and Turkey.
On Monday, Zentiva Romania informed
the Bucharest Stock Exchange that its majority shareholder Sanofi has decided
to sell its Romanian generic drug plant as part of a major divestment plan of
its EU generic drugs business.
A company spokesperson said the planned scope of the divestment is the generics business “related to Europe,” so it excludes Russia, the Commonwealth of Independent States (CIS) and Turkey. And it includes the two “dedicated manufacturing sites producing and distributing generics for the European market,” one in Prague (Czech Republic), and the other in Bucharest (Romania).
Former
Valeant executives arrested for fraud
Last week,
two former executives of Valeant Pharmaceuticals — Gary Tanner and Andrew Davenport, who had been the CEO of Philidor — were arrested on charges of running a fraud scheme that swindled millions of dollars out of Valeant. The fraud was allegedly conducted with the help of a mail-order pharmacy, that is now defunct.
According to
Preet Bharara, US Attorney for the Southern District of New York, the arrests
were part of an ongoing probe of the scheme.
The criminal
complaint alleges that Tanner and Davenport conspired to enrich themselves with
Valeant funds. The two helped Valeant set up Philidor in early 2013, which was primarily a vehicle to market and distribute
Valeant drugs.
According to
the complaint, Tanner focused on building Philidor’s business, resisted his superiors’ directives to line up other distributors for Valeant’s products and ultimately received a US $10 million kickback from Davenport.
The complaint alleges that in 2014, the two orchestrated Valeant’s agreement to buy an option to purchase Philidor, which cost Valeant at least US $ 133 million. More than US $ 40 million of that went to shell companies controlled by Davenport. One such shell company — called ‘End Game LP — gave a kickback of US $10 million to Tanner.
Homeopathy
products in the US may carry caveats soon
In a report on homeopathic advertising, the Federal Trade Commission (FTC) in the US said that homeopathic drugs should “be held to the same truth-in-advertising standards as other products claiming health benefits.”
Only the US
Food and Drug Administration (FDA) can prevent homeopathic marketers from
selling their products. The FTC has no teeth in the matter.
But very soon, homeopathic products could include statements such as ‘there is no scientific evidence backing homeopathic health claims’ and ‘homeopathic claims are based only on theories from the 1700s that are not accepted by modern medical experts.’
However, this may not affect sales of homeopathic products. There are claims that such statements could backfire because homeopaths and those who believe in homoeopathy don’t trust modern medicine. They could also believe that if
homeopathy has been around for that long, it must work.
This is not the first-time homeopathic medicines would carry caveats. In 1988, the FDA had struck a deal where it agreed that homeopaths could be self-regulating, if they include a disclaimer that their claims haven’t been evaluated by the FDA.
In February
this year, PharmaCompass had carried a news nugget on Professor
Paul Glasziou, a leading academic in evidence-based medicine at Bond
University, who had declared homeopathy as a “therapeutic dead-end”
after a systematic review concluded the controversial treatment was no more
effective than placebo drugs.
Cancer
clinical trials exaggerate benefits of new drugs, say oncologists
Two cancer physicians argue that large clinical trials — required for approval of new cancer drugs in the US — often overstate the effectiveness of the treatment in the real world.
During
cancer clinical trials, some volunteers take the experimental drug, while
others receive standard care with existing drugs. The groups are then compared
to see if their tumors have shrunk, how long it takes for the tumors to return,
and how long do the patients survive. This way, the trial sees whether the
experimental drug is safe and effective and can be sold to patients in the US.
The process
is based on the premise that trials give an accurate indication of safety
and efficacy among cancer patients in general, and not only those who are
eligible for and selected for the trial.
The trouble
is, participants in clinical trials are unlike the overall cancer population,
point out oncologists Dr. Sham Mailankody of Memorial Sloan Kettering Cancer
Center and Dr. Vinay Prasad of the Oregon Health and Science University in JAMA
Oncology. They’re younger, healthier, wealthier, better plugged in to the healthcare system, and better educated.
According to
these oncologists, if cancer patients are similar in age, socio-economic
status, have presence of other (similar) illnesses, and other
characteristics as those in a clinical trial, they might do as well. But for
everyone else, the trial results probably promise more than the drug can
deliver.
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https://www.pharmacompass.com/radio-compass-blog/china-shuts-plants-of-major-antibiotic-producers-to-fight-pollution-more-troubles-for-teva
#PharmaFlow by PHARMACOMPASS
24 Nov 2016
