Market Place
In
its continuous endeavor to bolster the competitiveness of the generics
market, the US Food and Drug Administration (FDA) updated its list of ‘off-patent, off-exclusivity drugs without an approved generic’.
The
agency updates this list every six months to improve transparency and to
encourage the development and submission of abbreviated new drug applications
(ANDAs) in markets that have little competition.
The
latest compilation by the FDA, which was published in June, contains 452
entries with 307 classified as Part I (drug products for which FDA could
immediately accept an ANDA without prior discussion), 136 as Part II (drug
products for which ANDA development or approval may raise potential legal,
regulatory, or scientific issues that should be addressed with the Agency prior
to considering submission of an ANDA) and 9 products being added to the Appendix
which indicates one or more ANDAs referencing NDA drug products that have been
approved since the publication of the previous list.
View FDA's List of Off-Patent, Off-Exclusivity Drugs with No Approved Generics
Injectables make up one-third of the products in June list
A
total of 69 entries, which were present in the December 2019 compilation, are
missing from the recent compilation posted in June 2020, whereas 25 entries
have been added to the December list. The new additions are an outcome of drugs
for which patents and/or exclusivities expired after December 2019. Products
that have been added include the commonly used anti-cancer drug Docetaxel
as well as the peptic ulcer treatment Esomeprazole Magnesium suspension.
Almost one-third of the products in the latest list —158 out of 452 — are drug products delivered as injectables, while there are 83 entries for oral solid dosage forms (such as tablets, capsules and modified release forms).
In
2017, FDA had announced the Drug Competition Action Plan (DCAP)
to encourage robust
and timely market competition for generic drugs and help bring greater
efficiency and transparency to the generic drug review process, without
sacrificing the scientific rigor underlying their generic drug program.
In
February this year, as part of this initiative, the FDA had
approved the first generic of toxoplasmosis drug, Daraprim
(pyrimethamine),
the drug which made ‘pharma bro’ Martin Shkreli infamous in 2015 after he raised the price of the drug, first approved by FDA in 1953, from US$ 17.50 to US$ 750 per tablet.
To date, the FDA has focused its efforts under
the Drug Competition Action Plan on three key areas:
1. Improving the efficiency of the generic drug development, review, and approval process.
2. Maximizing scientific and regulatory clarity with respect to complex generic drugs.
3. Closing loopholes that allow brand-name drug companies to “game” FDA rules in ways that delay the generic competition.
View FDA's List of Off-Patent, Off-Exclusivity Drugs with No Approved Generics
New guidance on CGTs to improve generic competitiveness
In March 2020, FDA had issued the guidance on Competitive Generic Therapies (CGTs). This guidance describes the process
that potential ANDA applicants should follow to request designation of a drug
as a CGT. It also outlines the criteria for designating a drug as a CGT,
provides information on the actions FDA may take to expedite the development
and review of ANDAs for drugs designated as CGTs, and explains how FDA
implements the statutory provisions providing for a 180-day exclusivity period
for certain first approved applicants that submit ANDAs for CGTs.
An
example of the FDA improving generic competitiveness through their various
initiatives is the case of the suspension form of Pfizer’s
Revatio,
which contains the same active ingredient as Viagra (sildenafil)
and is indicated for the treatment of pulmonary arterial hypertension (PAH).
The
drug was first approved in 2012 and generated sales of US$ 227 million in 2018. Since the approval of the first generic in May 2019, there are now seven approved generics of the drug on the US market. As a result, Pfizer reported a 37 percent drop in sales to US$ 144 million in 2019.
View FDA's List of Off-Patent, Off-Exclusivity Drugs with No Approved Generics
Impressions: 57843
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#PharmaFlow by PHARMACOMPASS
16 Sep 2020
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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: 54733
https://www.pharmacompass.com/radio-compass-blog/top-drugs-and-pharmaceutical-companies-of-2019-by-revenues
#PharmaFlow by PHARMACOMPASS
29 Apr 2020
In the third last week of 2017, Phispers takes a look at the steps being taken by Teva’s new CEO Kare Schultz to pull the drugmaker out of doldrums. Former CEO of Teva, Jeremy Levin, on the other hand, cited five reasons behind the Israeli drugmaker’s downfall. Meanwhile, the Cancer Research Institute undertook a comprehensive study of the global clinical landscape for immunotherapies. Its report found significant immuno-oncology agents in development. The USFDA found a 14 percent reduction in the usage of antibiotics in food producing animals. Regulatory issued cropped up in Bangladesh and India. And Viagra finally faced competition from generics in the US.
As Teva’s new CEO plans 10K lay-offs, former CEO cites reasons behind its downfall
In November-end,
Kare Schultz, the new CEO of the Israeli generic drug giant Teva Pharmaceutical
Industries, shook its top order and booted out Michael Hayden, the
chief scientific officer, Rob Koremans, head of global specialty medicines, and
Dipankar Bhattacharjee, head of the global generic medicines group.
This month has
brought more bad news for Teva’s employees. Schultz is considering cutting as many as 10,000 jobs, or
nearly 15 percent of the total jobs at the beleaguered drug maker, in order to
reduce expenses and pull it out of the US$ 35 billion debt burden it undertook
when it decided to acquire Allergan Plc in 2015.
With these job cuts, Teva hopes to reduce its expenses by US$ 1.5 billion to US$ 2 billion over the next two years. “No final decision has been taken, and the targets may be modified, with a range of 5,000 to 10,000 jobs being discussed,” a Bloomberg
news report quoted sources as saying.
Meanwhile, in an
interview published in Globes (Israel’s financial newspaper), the former CEO of Teva — Jeremy Levin — has thrown more light on what may have caused the generic drug giant’s downfall. Levin, a non-Israeli, had quit as the CEO of Teva four years ago.
In the interview, Levin cited five reasons behind Teva’s downfall — the attack on Mylan, the acquisition of Allergan,
the acquisition of Rimsa, the failure to build
a significant innovative business and the failure to improve the generics business.
“The drop in prices in the generics market was also expected… When I got to Teva, everything was already clear — the expected consolidation of drug purchasers and the growing competition from India and China,” Levin said.
According to Levin, 90 percent of the prescriptions now written in the US are generics prescriptions. “But in order to maintain profit margins in such a competitive market, you have to renew yourself more quickly than the market,” Levin added.
Data-integrity
concerns uncovered in Bangladesh; FDA observations at two Indian firms
Bangladesh’s efforts to emerge a
hub for generic drug product manufacturing suffered a serious setback this week as The Acme Laboratories Limited, based in Dhaka, was found to be non-compliant with Good Manufacturing Practices (GMP) by the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA).
In this first
inspection of the site, the inspectors uncovered “evidence of data integrity issues with GMP documents.” This brought up the question of the data “being used to support GMP decisions such as product release”. Acme is a manufacturer of Metronidazole tablets sold in the UK.
FDA observations at Glenmark and Shilpa
Medicare in India: In the past week, the USFDA also posted
its observations during recent inspections performed at Glenmark Pharmaceuticals and Shilpa Medicare in India.
Similar to the observations that resulted in Lupin receiving a warning letter recently, the FDA investigators expressed concerns over Glenmark and Shilpa’s failure to thoroughly review out-of-specification (OOS) investigations.
The inspection at Shlipa found that
the initial out of specification (OOS) laboratory results were invalidated in
favor of passing results without adequate investigation. Despite repetitive
complaints from the market, all investigations concluded the complaint
batch/product was acceptable.
During the inspection of Glenmark’s finished dosage manufacturing facility located at Baddi, India, the inspectors conclude that there were “no written procedures for production and process controls designed to assure that the drug products have identity, strength, quality and purity they purport or are represented to possess”.
The FDA investigators also found “quality documents shredded in the teeth and surrounding internal moving parts” of a shredder located in the Regulatory Affairs staff room at Glenmark. The documents (that were destroyed) included forms and chromatographs.
At Shilpa, the software in quality control used to conduct high performance liquid chromatography (HPLC) analysis of finished products for unknown impurities, was “configured to permit extensive use of multiple processing methods without scientific justification”.
During the analysis
of impurities, analysts could change integration parameters for each sample run
which included parameters such as inhibit integration, peak slice minimum area,
sensitivity, baseline point peak group start and peak group end.
Observations similar
to those at Glenmark and Shilpa sites
have resulted in the FDA issuing warning letters to the concerned companies.
However, it remains to be seen how well these companies address the concerns of
the regulators.
FDA report finds
reduction in usage of antibiotics in food producing animals
All those awareness campaigns on how antibiotic use in food producing animals to promote growth and prevent illness fuels dangerous, antibiotic resistant “superbug” infections in human beings seems to be bearing fruit.
A recent report by the US
Food and Drug Administration, titled ‘2016 Summary Report on Antimicrobials Sold or Distributed for Use in Food-Producing Animals’, shows that the sale
and distribution of antibiotics approved for use in food-producing animals in
the United States decreased by 10 percent from 2015 to 2016.
According to food
and consumer health groups, this is the first such decline in year-on-year
sales since the FDA began collecting data in 2009. For several years now,
scientists have cautioned the regular use of antibiotics to promote growth and
prevent illness in healthy farm animals.
A Reuters report said several American food companies, including McDonald’s and Tyson Foods, have stepped up efforts to curtail, and in some cases eliminate, antibiotics in their products.
Last month, the
World Health Organization had urged farmers to completely stop using
antibiotics to enhance growth of farm animals and to prevent disease in the healthy
ones.
2,004
immunotherapies under development, says Cancer Research Institute study
Advances
in immuno-oncology (IO) are changing the standard of care for patients with
many types of cancer. The Cancer Research Institute (CRI), a leading non-profit
organization, undertook an analysis of global IO clinical landscape (from
pre-clinical development to regulatory approval). And in its report, CRI has
quantified a significant number of IO agents in development. The institute is
dedicated exclusively to IO, also known as cancer immunotherapy.
The
report, titled, “Comprehensive Analysis of the Immuno-Oncology Landscape,” tracks 2,004 IO agents,
of which 940 are already in clinical development.
According to Aiman Shalabi, CRI’s chief medical officer and director of the Anna-Maria Kellen Clinical Accelerator, the institute has for the first time “established a bird’s eye view of the entire immunotherapy landscape spanning the planet”.
Immunotherapies for the treatment of cancer are therapies that simulate the body’s immune system to fight the disease. The net result of this targeted approach is decreased toxicity and increased efficacy of immunotherapy.
“This is the first independent analysis that quantifies and confirms the level of excitement and potential of immuno-oncology,” Shalabi said.
There
are 344 cancer vaccines in human studies, and 224 are clinical-stage cell therapies,
the report said.
Five trends
that are impacting the US drug wholesaling industry
Adam J. Fein,
President of Pembroke Consulting and CEO of Drug Channels Institute (DCI), has
highlighted five significant industry trends
affecting the US drug wholesaling industry. The trends had been published in an earlier article, which was an excerpt from DCI’s 2017–18 Economic Report on
Pharmaceutical Wholesalers and Specialty Distributors.
“Many of these issues are headwinds for the wholesalers. The profit declines and negative trends partly explain why, when compared with last year’s report, the stocks of the largest public wholesalers are valued at a steeper discount to the overall stock market average,” said Fein.
1. Revenue growth will continue to be slow as brand-name drug inflation falls. Profits from brand-name drugs will remain under pressure. “Wholesalers will benefit from growth in demand for prescription pharmaceuticals and the corresponding increase in drug spending,” Fein said.
2. Wholesalers’ profits from generic drugs will remain below historical levels due to generic deflation and pharmacy negotiations.
“Over the past four years, prices of generic drugs have been highly volatile. Wholesalers initially profited from generic drug inflation from 2013 to 2015. However, generic deflation, combined with lower gross margins, has significantly reduced wholesalers’ total gross profits from generic drugs in 2016 and 2017,” Fein said.
3. Wholesalers
will be forced to alter conventional pricing and contracting approaches to
address profit challenges of specialty pharmacy drugs.
“Pharmacy industry revenues are shifting from traditional brand-name drugs to specialty drugs. We project that in 2021, specialty drugs will account for 42 percent of the pharmacy industry’s revenues,” Fein said.
4. Multifaceted
partnerships will secure wholesalers' role with certain channels.
“Retail chains continue to shift away from self-warehousing in favor of direct-store deliveries from a wholesaler. As retailers eliminate self-warehousing capabilities, full-line wholesalers become virtually impossible to displace for traditional drugs dispensed by retail pharmacies,” Fein said.
5. Wholesalers
will still be unlikely to profit from biosimilars over the next few years.
Regulatory uncertainty and legal challenges from manufacturers of biological reference products have delayed the launch of biosimilars. “We expect that even if these products launch, payers, PBMs (pharmacy benefit managers) and prescribers will control access and product selection,” he added.
Generic
versions of Viagra from Teva and Pfizer launched in the US
This week, Viagra was subjected to competition in the US from a generic
from Teva Pharmaceuticals US.
Viagra is the brand name for Pfizer’s sildanefil, a drug for erectile dysfunction (ED)
that hit the market in 1998. This popular drug, also known as the little blue
pill, posted over US$ 1.5 billion in revenues in 2016.
Though Viagra’s patent will expire in April 2020, a deal
negotiated four years ago allows Teva USA to start selling a generic
version of Viagra in the US
from December 11, 2017.
However, Pfizer is not taking things lying down. The pharma giant will counter Teva’s generic with its own generic version of Viagra, a white pill, manufactured by its subsidiary Greenstone LLC. Though the original little blue pill is priced at US$ 65, Greenstone’s copy is priced at US$ 30 to US$ 35 a pill.
The launch of
Viagra had changed the American society in many ways. And the launch of Viagra
generics too is likely to have an impact. Availability of Viagra had helped
approximately 18 million men in the US, who suffered from ED, said a study
published in the American Journal of Medicine.
Impressions: 4811
https://www.pharmacompass.com/radio-compass-blog/teva-plans-10-000-job-cuts-former-ceo-cites-reasons-for-the-downfall-data-integrity-concerns-emerge-in-india-and-bangladesh
#PharmaFlow by PHARMACOMPASS
14 Dec 2017
This
week in Phispers, we bring you the latest twists in the GSK-Gilead rivalry over
HIV drugs. India, which recently banned beef nationwide, plans to now replace
gelatin with cellulose-based capsules. A lawsuit in the US says Mylan may have
overcharged the government US$ 1.27 billion in the form of rebates on EpiPens.
And, there is an update on the opioid crisis. Read on.
After beef, India mulls banning animal-based gelatin capsules
As India deals with the aftermath
of the controversial cattle trade ban, the Health Ministry is reviewing a proposal to replace gelatin capsules with cellulose-based capsules which are of plant origin and are “safe for use” as compared to animal-based gelatin capsules. Various stakeholders, NGOs and consumers have 21 days to weigh the pros and cons of this proposal and respond.
India’s ministry of health and family welfare constituted an expert committee on March 20 this year to address all technical issues pertaining to replacement of gelatin capsules with cellulose-based capsules for encapsulation of drugs.
The Indian government's ban on the
trade of cattle for slaughter threatens US$ 4 billion in annual beef exports and millions of
jobs if the government does not revoke it.
Indian meat traders, under the
aegis of the Qureshi Action Committee and other trade and industry
associations, plan to petition India's Supreme Court to get the government
order revoked.
As Pfizer
hikes price of 91 drugs, Maryland enacts law to curb generic drug price gouging
Last week, we had shared our list of drugs with ‘no patents and no competition’.
While our list provides tremendous opportunities for generic companies in the short-term, we also warned that the FDA’s continued focus on accelerating review of these drugs will require companies to rely on strategies less opportunistic than price gouging, to drive their future business growth.
On
October 1, 2017 Maryland will become the first state in the United States to enact a law prohibiting “price gouging” by generic pharmaceutical manufacturers. The Bill was passed by the Maryland General Assembly on April 20, 2017. On May 26, Maryland Governor Larry Hogan sent a letter to the Speaker of the
House stating that he would allow the bill to become law without his signature.
The move coincides with Pfizer
hiking the price of 91 drugs by an
average of 20 percent so far this year in the United States. This includes
price hikes for its erectile dysfunction treatment, Viagra, and
its pain drug, Lyrica, on
June 1.
There are two essential provisions of the Maryland Bill. First, it prohibits a generic drug manufacturer or wholesale distributor from engaging in price gouging in the sale of an “essential off-patent or generic drug.”
Second,
the Bill authorizes the Maryland Medical Assistance Program (MMAP) to notify
the Maryland Attorney General of a price increase when the Wholesale
Acquisition Cost (WAC) of a prescription drug increases by at least 50 percent
from the WAC within the preceding one-year period. Or, when the price paid by
MMAP would increase by at least 50 percent from the WAC within the preceding
one year period and the WAC for either a 30-day supply or a full course of
treatment exceeds US$ 80.
Mylan may have
received US$ 1.27 billion more in rebate for EpiPens
In
the US, Senate Judiciary Committee Chairman Charles Grassley released a Medicaid
investigator's report which highlighted that Mylan’s EpiPen may have received US$ 1.27 billion more from the rebate program from 2006 through 2016 than what the company was entitled to receive.
The
amount is nearly three times a proposed settlement that the company had
announced in October 2016.
Earlier,
Mylan had said it would return US $465 million
to the government as part of settlement negotiations with the Department of
Justice (DOJ). Talks with the DOJ continue.
Senator Grassley has been involved in a long exchange with Mylan questioning
the significant price-hikes which the company had implemented over the years.
The
EpiPen auto-injector, used to treat allergic reactions, cost US$ 57 a shot when
Mylan purchased it in 2007. However, a series of price increases has raised the cost
to more than US$ 600 for a pair of EpiPens.
Before the price hike controversy hit Mylan, the Epipen generated more than US$ 1 billion in sales and contributed about 40 percent to Mylan’s overall profits.
GSK, Gilead’s HIV contest heats up, as GSK goes for priority review
Two
of the top 10 fastest growing drugs in 2016 were those used to treat HIV. GlaxoSmithKline’s Triumeq (abacavir,
dolutegravir, lamivudine) and Gilead’s Genvoya (elvitegravir,
cobicistat, emtricitabine, tenofovir alafenamide), both generated a
sales growth in excess of US$ 1 billion.
For
a long time, Gilead dominated the HIV market. But GSK fought back recently. In
an effort to stay ahead in the game, GSK used a priority review voucher,
for which it paid US$ 130 million, to shave four months off its application approval process.
ViiV Healthcare, the global specialist
HIV company majority-owned by GSK, with Pfizer Inc and Shionogi Limited as its shareholders,
announced regulatory submissions to the European Medicines Agency (EMA) and US
Food and Drug Administration (FDA) for the first HIV maintenance regimen
single-tablet, which comprises of only two medicines. The two-drug regimen
contains dolutegravir (Tivicay, ViiV
Healthcare) and rilpivirine (Edurant,
Janssen Sciences Ireland UC).
However,
don’t count Gilead out. In four late-stage studies, the US company's new drug
bictegravir was found to be as effective as GSK's established dolutegravir,
which has been the cornerstone of the British group's growing HIV business in
recent years.
This
year, Gilead plans to apply for regulatory approval to sell its combination of
bictegravir and emtricitabine/tenofovir alafenamide
(FTC/TAF), with a submission in the US in the second quarter and in Europe in
the third quarter.
If
Gilead uses a priority voucher at the US FDA, it could launch in the US market
in the first quarter of 2018, industry analysts said.
Mallinckrodt
explores divestment of its generics business
Mallinckrodt Plc plans to sell off its generic drug unit in a deal that could fetch the company around US$ 2 billion. The move would also help the specialty
pharmaceutical maker shift towards higher-margin branded drugs.
Mallinckrodt's generics unit has
seen its sales plummeting, in part because some of its products include
opiate-based pain killers, which have fallen out of favor with doctors due to
their addictive potential.
The divestment would complete the company’s gradual shift away from its original focus on generic drugs and nuclear imaging towards branded specialty pharmaceuticals, which now make up for bulk of its revenues.
Between 2015 and 2016,
Mallinckrodt's generic drug sales declined around 18 percent, to just over US$
1 billion. During the same period, sales of branded specialty drugs increased
by around US$ 2.3 billion.
The England-based Mallinckrodt has reportedly hired investment bank Credit Suisse
Group AG to run a sale process for the unit.
Canadian researchers trace
the origins of the opioid crisis, as Ohio sues drug makers
Last week, the state of Ohio in
the US sued five major drug manufacturers, accusing them of misrepresenting the risks of prescription
opioid painkillers that have fueled a skyrocketing drug addiction epidemic.
Opioid drugs, including
prescription painkillers and heroin, killed more than 33,000 people in the
United States in 2015, more than any year on record, according to the US
Centers for Disease Control and Prevention.
Canadian researchers have traced
the origins of the current opioid crisis to a letter published in the New England Journal of Medicine (NEJM) in 1980,
which stated that opioids were not addictive. The original letter
titled ‘Addiction Rare in Patients Treated with Narcotics’, was just a
paragraph long.
The lone evidence the letter cited
was an anecdote that out of 11,882 hospitalized patients treated with
narcotics, only four patients with no history of addiction became addicted.
The journal's prestige helped fuel
this misguided belief. The letter was cited over 600 times, usually to argue
that opioids were not addictive.
Last week, the NEJM published an unusual warning for readers about the 1980 letter.
The editor's note on the original letter in the NEJM reads,
"For reasons of public health, readers should be aware that this letter
has been 'heavily and uncritically cited' as evidence that addiction is rare
with opioid therapy."
The five companies
Ohio sued were Purdue Pharma LP, Johnson & Johnson's Janssen Pharmaceuticals Inc unit, a unit of Endo International Plc, Teva Pharmaceutical Industries Ltd's Cephalon unit and Allergan Plc".
Impressions: 3174
https://www.pharmacompass.com/radio-compass-blog/after-beef-india-may-ban-gelatin-capsules-gsk-gilead-s-hiv-race-heats-up
#PharmaFlow by PHARMACOMPASS
08 Jun 2017
Yesterday, on July 1, 2015, the Drug Supply
Chain Security Act (or Drug Quality
and Security Act) became effective in the United States.The law is designed to secure the supply chain of
medicines and restrict counterfeit drugs, an industry estimated to be bigger
than Pfizer and GSK combined.
Laws against counterfeit drugs have also led to the arrest of Toyota’s highest-ranking female employee for alleged smuggling banned painkillers from the U.S. to Japan… What exactly are counterfeit drugs? An
estimated market of $75 billion, by the World Health Organization’s own admission, “counterfeit
drug is defined differently in different countries”. What the FDA calls “fake medicine”, WHO calls any medicine, “which is deliberately and fraudulently mislabeled with respect to identity and/or source”. For this reason, Toyota executive Julie Hamp’s efforts to “disguise illegal drug tablets” of painkiller oxycodone, legal with a prescription in the U.S., while a narcotic in Japan, would also fall under the same, loose classification. Why is it such a big issue? Counterfeit
drugs present a big challenge for users of medicines since there is no easy way
for patients to know whether or not the medicines they consume are safe.The WHO believes
that between 1% and 10% of drugs sold around the world are counterfeits and
this number could be as high as 50% in some countries. The primary distribution channel for such products are
illegal pharmacies operating over the internet. However, it is when fake drugs get
mixed with the normal medicine supply chain that countless horror stories get
reported. We have decided to cover some headlines made in recent times. Recent impact of counterfeit drugs- 365 children died in Panama due to a “toxic cough syrup” in which pharmaceutical manufacturers used toxic brake fluid component, diethylene glycol instead of glycerine. - FDA
discovered
that foreign distributors had supplied unapproved, counterfeit versions of Roche’s Altuzan 400mg/16ml (bevacizumab), an injectable cancer medication unapproved in the United States but approved in Turkey. Lab tests found
that the injections contained no active ingredient. - Counterfeit
versions of orlistat (Alli), GlaxoSmithKline’s over-the-counter weight-loss medication, were distributed over the internet, which did not contain the active ingredient. The fake product had been made with varying amounts of a controlled substance called sibutramine instead (anorexiant, removed from the US market due to concerns about heart attack and stroke). - A
brand of Viagra in
India, Kamagra, could not be sold outside India due to patent laws. So while Kamagra
was not a counterfeit drug in India, the success of Kamagra made it available
in other countries at prices much lower than Viagra. - In early 2008, ‘fake’ heparin based medicines caused deaths in the U.S. and other parts of the world. Chinese producers, trying to realize cost saving opportunities, had added a potentially toxic substance called ‘over-sulphated chondroitin sulphate’ to pharmaceutical grade heparin. The counterfeit product was cheaper to make, did not offer the intended therapeutic effect and was difficult to differentiate with existing test methods. - FDA discovered counterfeit versions of Roche’s cancer drug Avastin had entered the U.S. supply chain. Two Turkish nationals were arrested for shipping the drugs to the United States with false customs declarations.
- A physician, supplied with a research version of onabotulinumtoxinA (Botox), which was much more concentrated than the actual dosage, and not intended for human use. The research version resulted in respiratory paralysis and near death for several patients, including the physician who was using it himself. A very profitable businessAn expert estimates that counterfeit drugs are significantly more profitable than selling illegal drugs like heroin or cocaine. A
$1000 investment in counterfeit prescription drugs can result in a $30,000
return, which is 10 times the profit rate of trafficking heroin. Another source reported that selling counterfeit Viagra (sildenafil) “can be as much as 2000 times more profitable” than selling cocaine.Finally, the criminal penalties for the sale of
counterfeit medications are far less than the penalties for selling illegal
narcotics. Given the variation in global prices of the same drug, supply of medicines with incorrect documentation
through internet based models is common practice. An international effort, Operation Pangea VIII, earlier in June, shut down 2,800 websites across, 115
countries and seized medicines worth $81 million. Bring it on! In addition to restricting the entry of
counterfeit products at different ports, FDA scientists have developed a counterfeit detection device, CD-3. A battery-operated, hand-held and
inexpensive tool, using CD-3 costs a
fraction of the price of existing laboratory-based and field-deployable
technologies. Africa, where the counterfeit drug problem
is the most prevalent, has also initiated trials of the CD-3 device. While detection is only part of the
solution, laws designed to implement product
serialization, a comprehensive system to track and trace prescription drugs
through the entire supply chain, have been drafted. ChallengesThe intent of track and
trace systems is to enable comprehensive product traceability (down to lot
number details) from the manufacturer to the patient. Europe, India, Nigeria, Brazil, China have all announced
measures to combat the counterfeit drug problem. However, there are differences in each country’s approach towards the implementation of product serialization. The lack of harmonization, to achieve compliance in
different countries, will impact production and packaging processes of many
pharmaceutical manufacturers with global operations. Given the scale of this
endeavor, the U.S. planned implementation timeframes for the Drug Supply Chain
Security Act are stretched across a 10-year period. Digital
solutions?In the meantime, some
pharmaceutical companies are already moving ahead of the curve. EMD Serono,
part of Merck
KGaA, launched a mobile application called Check My Meds TM for product verification and is already
available for download for U.S. patients.As some medicines and such apps are not available yet all over the world, where ever you are, it’s important to be careful, since problems with counterfeits can occur everywhere on
the planet.
Impressions: 2599
https://www.pharmacompass.com/radio-compass-blog/counterfeit-drugs-toyota-s-highest-ranking-female-employee-arrested-it-s-time-to-understand
#PharmaFlow by PHARMACOMPASS
02 Jul 2015
A clinical study published in one of the leading oncology journals, Cancer, shows that Cimetidine can be synergized with other drugs, including existing therapies, and that its potential as an anti-cancer therapeutic should be explored much further.
Cimetidine has historically been used to treat indigestion through its ability to block histamine receptors in the gut. A widely available generic, Cimetidine was launched by GlaxoSmithKline under the trade name Tagamet. In some countries, like the USA, the product is available over-the-counter and is used for treating ulcers and heartburn.
The authors in their research share abundant pre-clinical and clinical evidence which demonstrate the therapeutic effects of Cimetidine in a range of cancers, especially cancers of the gastrointestinal tract, renal cell carcinoma and melanoma.
Recycling old drugs makes drug repositioning, or repurposing, an attractive form of drug discovery and accounts for approximately 30% of the newly approved drugs and vaccines by the FDA (US Food and Drug Administration) in recent years.
An enormous source of profits for the pharmaceutical industry and one of the most famous examples of drug repositioning is Viagra. Viagra was originally identified in connection with angina, and was successfully repositioned for erectile dysfunction.
The ReDO project (the repurposing drugs in oncology project), an international global collaboration of researchers, is dedicated to promoting common medicines such as mebendazole (for threadworm infections), nitroglycerin (used to treat angina), itraconazole (broadly used anti-fungal), diclofenac (a commonly prescribed painkiller) and clarithromycin (an antibiotic) as anti-cancer therapies.
The team of researchers combines the expertise of the Anticancer Fund, which is focused on expanding cancer treatment options by repurposing drugs, and Global Cures, a non-profit, medical research organization dedicated to curing patients with cancer.
The authors believe that, should positive results be obtained in an underway clinical trial that is studying the effect of Cimetidine in Colorectal Cancer, the focus on the potential of Cimetidine as an anti-cancer therapeutic will be re-ignited.
Drug Repositioning has been subject to extensive studies over the past few years and there are numerous examples of successful repositioning of products. Success of the ReDO project would allow cheaper access to solutions in the fight against cancer and once again support the case of looking at existing drugs instead of only focusing on novel, and potentially expensive treatments. It indeed brings a lot of hope for cancer patients since many existing treatments carry unwelcome side effects, and so existing drugs whose effects are already well understood and documented may well be utilized to assist treatment without the risk and without the massive cost and side effect implications.
Impressions: 2249
https://www.pharmacompass.com/radio-compass-blog/can-cimetidine-a-common-antacid-be-repurposed-for-cancer
#PharmaFlow by PHARMACOMPASS
12 Mar 2015
A recent study published in the Journal of the American Medical Association (JAMA) showed that patients who received the anticoagulant fondaparinux (Arixtra®) and had experienced a certain type of heart attack had a lower risk of major bleeding events and death, both in the hospital and after six months, compared to patients who received low-molecular-weight heparin (LMWH).
The authors analyzed data from a Swedish registry, which included 40,616 patients who had experienced an NSTEMI (non-ST-segment elevation myocardial infarction). A certain pattern on an electrocardiogram following the heart attack was observed, and 14,791 patients (36.4 percent) received fondaparinux, while 25,825 (63.6 percent) received LMWH.
Fondaparinux, an injectable blood thinner that fights clots in the legs (deep vein thrombosis – DVT) and lungs (pulmonary embolism – PE), is a synthetic pentasaccharide, which is difficult to manufacture on a commercial scale.
Arixtra belonged to GSK as recently as 2013, when it was sold off to the South African company Aspen Global Incorporated. Due to Aspen’s lack of a sales representative in the US, they were forced to enter into a $300 million agreement with Mylan for the US market, through which Mylan would pay Aspen $225 million upon completion of the transaction, and an additional $75 million would be held in escrow until certain conditions were met. Apotex had previously been given the rights to sell the authorized generic of Arixtra, the rights of which would eventually transfer to Mylan, which was scheduled to occur by the end of 2014.
Arixtra and the authorized generic of Arixtra had US sales of approximately $18.8 million and $95.3 million, respectively, for the 12 months ending on June 30, 2014, according to IMS Health.
Currently, the only approved product on the US market, other than Mylan’s, is that of Dr. Reddy’s, which was approved in 2011. Dr. Reddy’s entered into a partnership with the Australian company Alchemia, who claims to have been granted patents over novel synthetic pathways that prevent others from using Alchemia’s proprietary process to manufacture fondaparinux until at least 2022.
The regulatory filing review on PharmaCompass shows two suppliers of the key intermediates who have submitted USDMFs, along with multiple API DMF fillings indicating increased availability of the drug substance. This should overcome a major barrier to entry into the Fondaparinux business.
What makes us believers in Fondaparinux? Here are some facts:
$150 million – This is the size of the market in the United States alone.
There are only 2 approved US marketing authorization holders (Mylan and Dr. Reddy’s).
There are alternative API supply sources emerging other than Aspen (through Sanofi’s Sisteron site and Alchemia).
Blood thinners are a booming opportunity. Pfizer’s Eliquis, Bayer’s Xarelto, and Boehringer Ingelheim’s Pradaxa are all expected to achieve sales of more than $1 billion each.
There has been limited development activity in India as demonstrated by the trade data.
The high development costs will keep this market niche in the long run.
The recently published study data is extremely positive and will increase sales.
Impressions: 5018
https://www.pharmacompass.com/radio-compass-blog/fondaparinux-an-opportunity-worth-developing
#PharmaFlow by PHARMACOMPASS
11 Mar 2015
