Market Place
We usher in 2023 with the key highlights of the US Food and Drug Administration’s December 2022 list of Off-Patent, Off-Exclusivity (OPOE) Drugs with No Approved Generics. With this list, the FDA hopes to bolster competitiveness
in the generics market.The OPOE list gets updated every six months. Such updates are a part of FDA’s initiative to improve transparency and encourage the development and submission of abbreviated new drug applications (ANDAs) in markets with little competition.Since 2017, the FDA has been publishing the OPOE list of drugs without an approved generic. For a year now, the FDA has been publishing two versions of the OPOE list — one for prescription drug products and one for over-the-counter (OTC) drug products that are approved and marketed under a new drug approval (NDA).View FDA's 2022 List of Off-Patent and Off-Exclusivity Drugs (Free Excel)Four
new applications added to Dec 2022 list; 96 first generics approved last yearWhile the FDA’s June 2022 list of OPOE Drugs with No Approved Generics had 98 new applications for prescription drugs, the December 2022 list saw a sharp decline — only four new applications were added during this period. We had witnessed a similar trend in 2021 — the December 2021 list had only 16 new applications as
opposed to 35 new applications in the June 2021 list.The four new applications were for diclofenamide (a drug to treat glaucoma), ephedrine sulfate (a drug used to treat asthma and
heart failure that also acts as a central nervous system stimulant), meloxicam (an arthritis drug) and pemetrexed (a chemotherapy medication). In
May 2022, the FDA approved the first generics for pemetrexed injection
developed by several companies, including Accord Healthcare, Fresenius Kabi, Apotex, Qilu Pharmaceutical, Biocon, Dr. Reddy’s Laboratories and
Zydus, to treat non-small cell lung cancer (NSCLC) and mesothelioma. Almost one-third of the prescription products – 184 out of 505 – are drug products delivered as injectables, and 68 entries are for oral solid dosage forms (such as tablets, capsules and modified release forms).In the June 2022 list, a total of 60 OTC
drug products were listed. This time too, the same number of OTC drug products
figured in the OPOE list. These include antiseptic agent chlorhexidine gluconate,
non-steroidal anti-inflammatory drug ibuprofen, anti-allergy drug loratadine and painkiller acetaminophen. Of these, 19 are delivered as
oral solid dosage forms (such as
tablets, capsules and modified release forms).In 2022, the FDA approved 96 first generics. This is slightly higher than
the 93 approved by the agency in 2021.As the name suggests, “first generics” are the first approvals handed by the FDA to manufacturers to market a generic product in the United States. The agency considers first generics to be important to public health, and prioritizes review of these submissions.View FDA's 2022 List of Off-Patent and Off-Exclusivity Drugs (Free Excel)AbbVie’s Humira, Novartis’ Entresto to finally face generic competitionAbbVie is facing one of the steepest patent cliffs in the industry’s history, with Humira slated to face the onslaught
of eight biosimilars this year. The blockbuster drug had generated US$ 21.2 billion in 2021. Amgen’s Humira biosimilar – Amjevita – will hit the market this month. The other Humira
biosimilars that will be launched this year include Abrilada (Pfizer), Cyltezo (Boehringer), Hadlima (Samsung Bioepis), Hyrimoz (Sandoz), Hulio (Viatris) and Yusimry (Coherus BioSciences). In mid-December, Fresenius Kabi became the latest
company to win US approval for its Humira copycat — Idacio.Novartis’ heart failure drug Entresto will also go off patent this month. The blockbuster drug had generated US$ 3.5 billion in 2021.View FDA's 2022 List of Off-Patent and Off-Exclusivity Drugs (Free Excel)Our viewIn our previous OPOE drug listing, we had talked about FDA’s intent to bring down drug prices, with the agency putting 98 new applications of prescription drugs in the OPOE list for June 2022. That intent has only become stronger with the US Patent and Trademark Office (USPTO) and the FDA joining hands to promote
competition. The two bodies are working towards improving the patent system in an effort to stop its misuse through “patent thickets”, “evergreening” and “product-hopping”. With this clear intent to lower drug prices in the US, the OPOE lists for 2023 and beyond are likely to get more interesting. For now, all eyes are set on what generic competition will do to blockbusters like AbbVie’s Humira and Novartis’ Entresto.
Impressions: 2696
https://www.pharmacompass.com/radio-compass-blog/fda-s-list-of-off-patent-drugs-suggests-higher-approvals-of-first-generics-in-2022
#PharmaFlow by PHARMACOMPASS
05 Jan 2023
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While the world feels the heat of the Covid-19 pandemic with the global pharmaceutical supply chain getting impacted, normalcy is returning
to China. According to new reports, the production of drugs and APIs in China is also returning to normal.
In a press conference held by top Chinese officials this week, the country’s ministers highlighted that as of March 28, the average operating rate of industrial enterprises across China had reached 98.6 percent and the production of some key vitamin, antibiotic and analgesic raw material drug companies had returned to normal with yields of major products reaching above 80 percent.
Officials had paid heed to resumption of production
The officials
highlighted that during the critical period of epidemic prevention and control,
the Chinese government had paid close attention to the resumption of production
of API companies. After receiving reports that some companies in Hubei had not
resumed work, which would impact the supply chains of products like metronidazole, ibuprofen, and taurine, the
authorities urgently coordinated with the relevant departments of Hubei, other
provinces, cities and counties to carry out key scheduling for some API
manufacturers and actively organized employees to return to work.
However, despite
these initiatives, due to the impact of the epidemic, wherein some enterprises
had stopped production and subsequently faced challenges with logistics and
transportation difficulties, there was a shortfall in supply.
The export
volume of APIs did decrease this year compared with the same period last year
and the officials estimated that most products witnessed a drop of about 10 to
20 percent, and in some cases the decline of individual varieties had reached
30 percent. Repeated communications between the officials and these
companies revealed that the main contributor to the decline in exports was sea
freight, as international shipping had greatly reduced, and transportation
costs have also increased.
Although
international transportation has become a bottleneck for the supply of some
APIs, the press conference highlighted that the output of other APIs had
exceeded the level of the same period last year.
China to meet global demand for chloroquine
The officials
made a special mention of medications like chloroquine phosphate which have
received significant attention as a potential treatment of the novel
coronavirus. After chloroquine phosphate was identified as a potentially
effective treatment, the government worked with the two major API manufacturers
in China to organize the companies to meet international demand. For example, Chongqing Kangle Pharmaceuticals exported 4.9
tons of chloroquine APIs within five days.
This news from
China is encouraging to the global supply chain as following the rising interest in a chloroquine analog — Hydroxychloroquine (HCQ) — the
Indian government issued a directive which
prohibits the export of HCQ API and formulations made from HCQ. The directive
did, however, offer exemptions to exports from special economic
zones/export-oriented units and in cases where export is made to fulfill an
export obligation under any advance license issued on or before the date of the
notification.
Last week, Hungary, which is also one of the world’s largest exporters of HCQ, also banned the commercial export of the ingredient and the
United Kingdom (UK) banned the export of finished formulations of HCQ as part
of a list of 135 medicines posted that cannot be exported from the UK
because they were needed for the UK patients.
In early
March, the Indian government had also restricted the exports of
13 APIs along with some of their finished formulations. The list included paracetamol tinidazole metronidazole acyclovir vitamin B1 vitamin B6 vitamin B12 progesterone chloramphenicol and neomycin.
However, a recent report published in The Economic Times highlighted that out of 13 drugs whose exports were restricted, the government is likely to lift the ban on the following five APIs — paracetamol, tinidazole, metronidazole, ornidazole and azithromycin. There were
also reports of significant pressure from the US on the Indian government for products
like paracetamol and the officials expect the ban to be lifted in the coming
days.
The Chinese
officials further went on to provide assurances that the supply of chloroquine phosphate can be increased in accordance with international market demand and that China’s Ministry of Industry and Information Technology will also organize the implementation of monitoring and production scheduling of key products, coordinate and solve the export transportation difficulties encountered by enterprises and strengthen communication.
Our view
The press
conference highlighted that China attaches great importance to the safety of
the global pharmaceutical industry supply chain and President Xi Jinping had
promised at the G20 summit of member states on March 26 that China will
increase its efforts to supply APIs to the international community.
The Chinese
government is working earnestly to implement the commitment to maintain the
production of API manufacturers and ensure the safety and stability of global
industrial chain supply, the statement emerging out of the press conference
said.
Given the global pharmaceutical supply chain’s overwhelming dependence on China, the nation’s return to normalcy is a positive sign for countries across the world. For the time being, the pandemic has only increased the world’s dependence on China. All countries that want to reduce their reliance on China will take time not just to build capacities, but also to emerge out of the Covid-19 crisis.
Impressions: 1618
https://www.pharmacompass.com/radio-compass-blog/chinese-industrial-activity-revival-at-98-6-percent-officials-assure-of-api-supplies
#PharmaFlow by PHARMACOMPASS
02 Apr 2020
As we come to an end of the shortest month of the year, we are
back this week with another edition of PharmaFlow, a monthly
roundup of deals and investments from across the globe.
If you have been following pharma news, you would already know
that January was a big month for M&As. Here we look at some deals announced
last month, and hope our roundup gives you an insight into the breakthrough technologies and business trends of
tomorrow.
Big bang M&As: Sanofi acquires Bioverativ, Ablynx;
Celgene acquires Juno Therapeutics
The year started with big bang M&A deals and was the most active January for deal
making in over a decade with Sanofi and
Celgene
dominating the headlines.
French drugmaker Sanofi started off by announcing it had closed a deal to
acquire Biogen spinout Bioverativ, a maker of drugs for
hemophilia, for almost US$ 11.6 billion.
The second biggest deal in January, announced in the same week,
was the acquisition announcement of Juno Therapeutics by Celgene Corporation for approximately US$ 9 billion.
Click here to view the major deals in January 2018
(FREE Excel version available)
Juno is a pioneer in the development of CAR (chimeric antigen receptor) T and TCR (T cell receptor) therapeutics with a broad, novel portfolio evaluating multiple targets and cancer indications. This acquisition will add to Celgene’s lymphoma program, JCAR017. Regulatory approval for JCAR017 in the US is expected in 2019. With this acquisition, Celgene hopes to deliver a new CAR-T with peak sales of US$ 3 billion a year.
Sanofi, on the other hand, bet big on the fast-changing hemophilia market, where Bioverativ’s business is threatened by Roche and
developers like BioMarin and
Spark/Pfizer, who are
looking to disrupt the business with new gene therapies now in late-stage
development.
Recently, Roche won a nod for its
hemophilia drug Hemlibra.
Sanofi didn’t stop at the Bioverativ buy — it agreed to buy Belgian biotech company Ablynx for US$ 4.8 billion (Euro 3.9 billion), beating Denmark’s Novo Nordisk. Ablynx had earlier rejected a US$
3.2 billion (Euro 2.6 billion) offer from Novo Nordisk.
Ablynx specializes in the research of novel drugs based on nanobodies (which are found in the immune systems of llamas and alpacas). Ablynx partners with several of the world’s largest pharmaceutical companies.
Click here to view the major deals in January 2018 (FREE
Excel version available)
Sanofi and its
partners at Regeneron also announced they were boosting
their development budget for cemiplimab to a minimum of US$ 1.65 billion — one billion dollars more than what had been agreed upon in the development agreement signed three years ago.
Celgene buys Impact Biomedicines, a startup that bought Sanofi’s cast off drug
In January, Celgene also agreed to acquire Impact Biomedicines for US$ 7 billion, subject to
certain milestones associated with regulatory hurdles and sales performance.
Celgene’s buy was driven by its interest in Impact Biomedicines’ fedratinib, a kinase inhibitor that has shown promise as a potential treatment for myelofibrosis. Myelofibrosis is a group of rare cancers of the bone marrow in which the marrow is replaced by scar tissue and is not able to make healthy blood cells.
San Diego-based Impact Biomedicines had bought fedratinib — Sanofi’s cast off drug — in 2013. Fedratinib was a flop for Sanofi as patients began to develop a dangerous neurological condition tied to vitamin B deficiency called Wernicke’s encephalopathy. As a result, the US Food and Drug Administration (USFDA) put a clinical hold on it in 2013 and Sanofi ultimately shelved the effort. However, last fall, Impact Biomedicines began convincing regulators that patients can be protected from the lethal side effects of fedratinib.
Click here to view the major deals in January 2018
(FREE Excel version available)
The US$ 7 billion deal is structured in three parts,
with Celgene paying US$ 1.1 billion in cash upfront to Impact
Biomedicines. Celgene will pay an additional US$ 1.4 billion on receiving USFDA
milestone approvals.
Finally, Celgene will make payments depending on sales, with a maximum of US$ 4.5 billion due if annual net sales of Impact’s treatments exceed US$ 5 billion.
While the deal is considered a great buy for drug inventors, and that includes
John Hood, one of the co-inventors of fedratinib, analysts say the acquisition
may not be great for Celgene.
According to a Bloomberg report, Celgene’s shares are “suffering because the company promised investors the world, then significantly revised the planet’s size”.
In October 2017, Celgene had reported weak third-quarter
earnings and significantly cut its ambitious 2020 revenue guidance that it had
set in 2015.
Click here to view the major deals in January 2018
(FREE Excel version available)
Cast off natural products meet artificial intelligence in Pfizer’s deal with Adapsyn
In a deal valued up to US$ 162 million, Adapsyn Bioscience Inc announced it had completed a round
of financing that was co-funded by Pfizer R&D Innovate and Genesys Capital.
In addition, the company also announced a research collaboration with Pfizer Inc.
Adapsyn technology platform combines genomic and
metabolomic data with artificial intelligence and machine-learning to identify
novel, mechanistically diverse evolved small molecules.
Adapsyn’s technology could potentially help take much of the guess work out of the process of discovering truly novel compounds that exhibit new pharmacological signatures from natural products. The process to reveal novel chemistry and biology from natural product samples has historically been a very time- and labor-intensive process.
Under the terms of the research agreement, Adapsyn and Pfizer are working together to employ Adapsyn’s proprietary platform technologies with the goal to identify and test previously undiscovered natural products from Pfizer’s collection of microbial strains.
Click here to view the major deals in January 2018
(FREE Excel version available)
Indian firms on buying spree:
Ipca buys Pisgah Labs; Torrent expands in US
Two Indian pharmaceutical companies Ipca Laboratories and Torrent Pharmaceuticals also made news in the M&A space in January .
In June 2017, the USFDA had banned almost all drugs manufactured by India’s Ipca Laboratories at its facilities at Pithampur, Silvassa and Ratlam for violation of current good manufacturing norms (cGMPs).
While continuing to be on the import alert list of the USFDA,
Ipca Laboratories said its two subsidiaries have fully acquired US-based Pisgah Labs Inc for US$ 9.65 million.
Pisgah, a
contract manufacturer and developer of APIs and intermediates, will continue to
operate out of its North Carolina manufacturing facility under the Pisgah trade
name.
Meanwhile, Ahmedabad-based Torrent Pharmaceuticals announced the acquisition of Bio-Pharm Inc, a drugmaker based in Pennsylvania, US. The company did not
disclose the deal size or other financial details.
Bio-Pharm, a generic pharmaceuticals and over-the-counter (OTC)
drugs company, has a proven track record in the research and development and
manufacturing of oral solutions, suspensions and suppositories, it said.
Click here to view the major deals in January 2018
(FREE Excel version available)
With an annual revenue of more than US$ 911.8 million (INR 58
billion), Torrent Pharma is the flagship company of the US$ 2.9 billion (Rs 183
billion) Torrent Group.
Indian companies to bid for Sanofi’s European generics business: Indian drug companies — Aurobindo Pharma, Zydus Cadila, Torrent Pharma and Intas — also expressed preliminary interest in buying the European
generics business of Sanofi.
The Indian drug majors are positioned against top drugmakers in China, as well as several global private equity players. Therefore, the Indian drug majors may tie-up with strategic players to pitch for the Paris-headquartered drug major’s generic business.
Europe’s leading private equity player Apax Partners is joining forces with Zydus Cadila while Intas is backed by Temasek and Chrys
Capital.
In January 2017, Sanofi had said it plans to finalize the sale of its
generic drugs business by the end of 2018. The unit employs 3,000 people and
reported about US$ 977.25 (Euros 800 million) in sales in 2016.
Click here to view the major deals in January 2018
(FREE Excel version available)
J&J
opts out of the race for Pfizer’s US$ 20 billion consumer unit
The mother of all M&A deals would be the sale of Pfizer’s consumer health unit. It could be as big as all the M&A
deals announced in January put together.
Johnson & Johnson was once considered the strongest
contender for Pfizer’s consumer health unit. However, it announced last
month that it is pulling out of the race to buy Pfizer’s consumer health business.
Back in 2006, J&J had snapped up Pfizer’s previous consumer health business for US$ 16.6 billion. And the same was expected of J&J in 2018, with plans of Pfizer to put its consumer unit on the block. The unit makes Advil painkiller, Centrum multivitamins and Chapstick
lip balm.
Click here to view the major deals in January 2018
(FREE Excel version available)
J&J is cash rich — it is about to bring home US$ 12 million in overseas cash, thanks to new tax laws in the US. It also wants
to continue expanding its portfolio.
However, CEO Alex Gorsky told
investors the company would put a good chunk of that money back into R&D.
With J&J out, drugmaker GlaxoSmithKline and consumer goods group Reckitt Benckiser are left in the game. And the
two players are learnt to be preparing bids.
The deal could be a game-changer
for GSK or Reckitt by making them one of the biggest global players in consumer
health, which has emerged as a booming sector worldwide.
Though the company is yet to
make public any details about the sale process, a Reuters report
says Pfizer wants to sell this unit for no less than US$ 20 billion.
Click here to view the major deals in January 2018
(FREE Excel version available)
Our view
Experts predict that 2018 will
be a bumper year for M&As. The year began with more than enough signs that
validate this prediction.
During January, we saw biotech
M&As worth US$ 26.3 billion. According to Thomson Reuters data,
this is more than 80 percent of the value of all deals in 2016 and far ahead of
any comparable January tally in over a decade.
There is much consolidation
happening in generics. And biotech is also witnessing hectic M&A activity.
Deals in the biotech space are driven by the need for large drug makers to tap
the promising new medicines being developed by smaller rivals in order to rev
up their sluggish growth engines.
With new tax policies in the US,
stay connected with PharmaFlow to follow all the action.
Click here to view the major deals in January 2018
(FREE Excel version available)
Impressions: 3526
https://www.pharmacompass.com/radio-compass-blog/pharma-deals-investments-and-m-as-in-january-2018
#PharmaFlow by PHARMACOMPASS
22 Feb 2018
This week, Phispers brings you news on an apex court ruling in Canada that overhauls its patent law and makes it more NAFTA-friendly. While
a new director-general took office at the WHO, malware Petya stalled operations
at Merck. We also report on a warning letter to a heparin testing laboratory in
China, and how the FDA has proposed a delayed enforcement of new serialized
product identifier on drug packages by one year.
Heparin testing laboratory in China receives FDA warning
letter
In early 2008, ‘fake’ heparin-based medicines caused deaths in the US and other parts of the world. In a bid to realize cost-saving opportunities, Chinese producers had added a potentially toxic substance — known as ‘over-sulphated chondroitin sulphate’ (OSCS) — to pharmaceutical grade heparin.
The counterfeit product was cheaper to manufacture, did not offer
the intended therapeutic effect and was difficult to differentiate from heparin
using the existing test methods.
After the 2008 heparin crisis, the analysis of heparin and
heparin-related drugs has become of prime importance to the FDA.
Shandong Analysis and Test Center, a contract testing lab
situated in Shandong in China that analyzes samples of heparin and
heparin-related drugs for the presence of OSCS using nuclear magnetic resonance (NMR)
spectroscopy, received a warning letter after a January 2017 FDA inspection.
The inspectors found the laboratory routinely failed to establish
analytical system suitability while testing samples for OSCS. In one instance,
when the system suitability test failed, the lab did not investigate why the
equipment failed system suitability for detection of OSCS. It also did not
determine the reliability of other OSCS tests conducted prior to the system
suitability failure.
The warning letter said: “System suitability testing determines whether requirements for precision are satisfied and ensures the NMR spectrometer is fit for the intended testing before analyzing samples. It is critical that your system be demonstrated as suitable for detecting OSCS contamination in heparin to avoid the possibility of samples erroneously passing when an instrument is not working properly.”
In addition, analysts were unable to retrieve original electronic
data for analysis of heparin and heparin-related drug samples. During the
inspection, access to information necessary to conduct the inspection was also restricted.
FDA proposes delayed enforcement of DSCSA (track and trace
/serialization)
The US Food and Drug Administration (FDA) has proposed a delayed
enforcement of new serialized product identifier on drug packages and
verification requirements by one year. This draft guidance, published by the FDA last week,
could have major ramifications for the industry.
As part of the Drug Supply Chain Security Act (DSCSA) requirements, referred within some parts of the industry as either ‘track and trace’ or ‘serialization’, all drug manufacturers are required to begin affixing or imprinting a product identifier to each package and homogenous case of a product intended to be introduced in a transaction into commerce no later than November 27, 2017. Repackagers are required to do the same no later than November 27, 2018.
In the draft guidance, the FDA says it does not intend to take
action against manufacturers who do not affix or imprint a product identifier
to each package and homogenous case of products before November 26, 2018.
“This represents a one year delay in enforcement of the requirement for manufacturers to affix or imprint product identifiers. For the products that manufacturers introduce in a transaction into commerce before November 26, 2018, without a product identifier, FDA also does not intend to take action against manufacturers who do not use a product identifier to verify such product at the package level,” the draft guidance said.
“Almost all of the manufacturer requirements set to go into effect on November 27, 2017 would not be enforced” due to this proposed one year delay, an industry analysis said.
A delayed rollout will, however, still require “manufacturers to provide the transaction information, transaction history and transaction statement in electronic format only, except when selling directly to a licensed healthcare practitioner who is authorized to prescribe medication under State law, or to other licensed individuals who are under the supervision or direction of such a practitioner who dispenses product in the usual course of professional practice,” it added.
BASF announces significant enhancements in ibuprofen manufacturing capacity
BASF
is building a new plant to manufacture the active pharmaceutical ingredient (API) — ibuprofen — in Ludwigshafen, Germany. The plant is scheduled to come onstream in 2021.
The company is also expanding its ibuprofen capacities at its production site in the US, situated at Bishop (Texas), to fill the existing supply gaps for ibuprofen in the market. The expansion will come onstream in early 2018. The company is investing around US$ 226 million (€200 million) in both these projects.
Ibuprofen is used to treat pain, fever, and inflammation. The Ludwigshafen plant will be “the first world-scale ibuprofen plant in Europe,” Dr Markus Kamieth, member of the board of executive directors, BASF SE, said. With this investment, BASF aims to ensure high supply security for its customers and meet the growing global demand for the API.
After Sanofi, GSK forays into artificial intelligence by tying up with Exscientia
An increasing number of companies on both sides of the Atlantic
are applying artificial intelligence (AI) to drug research. The latest to join
the bandwagon is British drug major GlaxoSmithKline — the company unveiled a US$ 43 million strategic drug discovery deal with
Exscientia on July 1.
As per this tie-up, Scotland-based Exscientia will leverage its
AI-enabled platform with the expertise of GSK, in order to discover novel and
selective small molecules for up to 10 disease-related targets. In May,
Exscientia had signed a similar deal with Sanofi.
The AI-based drug discovery process harnesses modern supercomputers and
machine learning systems to predict how molecules will behave, and how they
could make a useful drug, thereby saving time and money on unnecessary tests.
AI systems already play a central role in other high-tech areas such as the
development of driverless cars and facial recognition software.
Besides Sanofi and GSK, Merck
and Johnson & Johnson are also exploring the potential of AI to help streamline the
drug discovery process.
Andrew Hopkins, CEO of Exscientia, said: “This agreement with GSK is the second we have signed in recent months with a top global pharma company. The alliance provides further validation of our AI-driven platform and its potential to accelerate the discovery of novel, high-quality drug candidates.”
However, big pharma is treading cautiously when it comes to AI. “It's still to be proven, but we definitely think we should do the experiment,” John Baldoni, GSK's head of platform technology and science, said.
Canada overhauls patent law; multinationals favored over startups
A Supreme Court
ruling in Canada last week overhauled its patent law. And now, the law will largely favor multinational patent holders over Canada’s own startups. According to news reports, the step may ease North American Free Trade Agreement (NAFTA) talks, due to begin in August.
This decision, aimed at reshaping intellectual property rights in
Canada, effectively lowers the bar to receive and defend a patent in the country,
tilting the playing field in favor of existing patent holders.
However, though the larger firms may have lauded the ruling, it threatens to hurt the domestic technology sector and undercut Prime Minister Justin Trudeau’s vision of reshaping Canada as a leader in innovative industries.
The Supreme Court ruled that a current standard, known as the “promise doctrine,” goes too far, because it allows for patents to be invalidated if an invention doesn’t do any of the things it promised.
The decision resolves an issue that had been flagged by the US in the NAFTA talks. The Supreme Court decision came after another ruling last week that ordered Alphabet’s Google to remove search results from websites offering goods that infringe on intellectual property.
The ruling “removes a key irritant,” Michael Geist, a law professor at the University of Ottawa, said in a written statement. “Combined with the Google case from earlier this week, Canada is now home to some of the toughest anti-piracy laws in the world along with some of the friendliest patent rules for patent holders,” Geist added.
Merck’s operations shutdown due to computer malware Petya
Last week, Petya/NotPetya cyberattack hit Merck
and several other companies. The cyberattack, known as ransomware, works by locking users out of
their computers and demanding a ransom in order to regain entry.
New Jersey-based Merck made the announcement of the
attack last week. Internal communications instructed employees to disconnect mobile devices from the network and refrain from posting on
social media.
The core technology in Petya is called ETERNALBLUE. According to news reports, it was developed by American spy agencies. It relied on bugs in Windows that Microsoft presumably wasn’t aware of until earlier this year.
Merck missed two critical opportunities earlier this year to
inoculate itself from this vicious cyberattack. In March, Microsoft had issued a critical bulletin advising IT
administrators of the steps needed to prevent hackers from using the
ETERNALBLUE technology to gain unauthorized access into their networks.
Then in May, the first global attack based on this exploit, known
as WannaCry, had spread widely, shutting down 16 hospitals in the UK. In the
aftermath of WannaCry, Microsoft issued yet another patch. In fact, most
prominent security firms worldwide asked companies to immediately employ these
crucial patches to prevent unauthorized access to private networks.
A Merck spokesperson said: “We have made good progress in our response to the June 27 global cyber attack…Government authorities working with us have confirmed that the malware responsible for the attack contained a unique combination of characteristics that enabled it to infect company systems despite installation of recent software patches.”
The Petya attack hit at least five other countries. In Ukraine,
the attack was being described as the biggest in the country's history.
Tedros Adhanom Ghebreyesus takes office as the new WHO director-general
On July 1, Dr Tedros Adhanom Ghebreyesus took over as director-general of the World Health Organization
(WHO). He succeeded Dr Margaret Chan.
Tedros was elected on May 23, 2017, by vote of WHO member states at the 70th World Health Assembly. The director-general is WHO’s chief technical and administrative officer and oversees the policy for WHO’s international health work.
This is the first time that member states at the World Health
Assembly selected a director-general
from among multiple candidates. In previous elections, a single nominee was
forwarded by the WHO executive board to the World Health Assembly for
consideration, a statement said.
Prior to his election as the director-general of WHO, Tedros served as minister of foreign affairs of Ethiopia from 2012 to 2016. He also served as the minister of health of Ethiopia from 2005 to 2012 where Tedros led a comprehensive reform effort of the country’s health system, including the expansion of the country’s health infrastructure.
“The right of every individual to basic health services will be my top priority. I will champion mechanisms to meaningfully listen to, learn from and engage people and communities — including migrant, displaced and disabled individuals; people living in rural, urban slum and low-income areas; and other vulnerable populations,” Tedros said in his vision statement.
Impressions: 2888
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#PharmaFlow by PHARMACOMPASS
06 Jul 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: 5511
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
Over
700 commonly used generic medicines were
recommended for suspension by the European Medicines Agency (EMA) based on data
integrity concerns, over clinical studies conducted at GVK Biosciences in
Hyderabad, India.What
will be the global fallout of the European decision? The European decision has
impacted products from companies such as:Abbott Laboratories, Accord Healthcare (Intas), Actavis, Alembic, Apotex, Betapharm (Dr. Reddy’s), Brown & Burk UK, Fair Med Healthcare AG, Glenmark, Lupin, Micro Labs, Mylan, Orion Corporation, Ranbaxy, Ratiopharm, Sandoz, Sanofi-Aventis, Stada, Teva, Torrent, Wockhardt, Zydus… and many, many more.The
original recommendation of suspending
some of the medicines
made in January 2015, was an outcome of an inspection of GVK Biosciences’ site in Hyderabad (GVK BIO is a Clinical Research Organization-
CRO) by the
French medicines agency (ANSM) through the EMA. The EMA stated in their official release: “The
inspection revealed data manipulations of electrocardiograms (ECGs) during the
conduct of some studies of generic medicines, which appeared to have taken
place over a period of at least five years. Their systematic nature, the
extended period of time during which they took place and the number of members
of staff involved cast doubt on the integrity of the conduct of trials at the
site.” 1000 drugs reviewed// 700
rejectedWhile
over 1,000 pharmaceutical forms and strengths were reviewed at the GVK site,
over 300 of them had sufficient supporting data available from other sources.
As a result, these medicines were allowed to remain on the market in the EU.However, for the over 700 other medicines, the EMA after its second review, maintained its previous recommendation of January 2015, to suspend medicines, where no additional supporting data from other studies was available. Only one exception after that second review was spared from suspension, as the company was able to address the EMA’s concerns: it was Bivolet Nebivolol (5 mg tablets/ marketing authorisation holder: Neo Balkanika EOOD).While the agency noted that “there is no evidence of harm or
lack of effectiveness linked to the conduct of studies by GVK Biosciences at
Hyderabad. Some of these medicines may remain on the market” if they are of critical importance for patients. However, the recommendation
will now be sent to the European Commission for a legally binding decision,
which will apply to Member States regardless of the decision taken in the
interim period.The updated list of medicines for which, the CHMP (Committee
for Medicinal Products for Human Use) recommends suspension, is available on the EMA website. Companies
are given 12 months to submit additional data. The potential global impact of the European
suspensions?The GVK Biosciences
scandal is almost as severe in magnitude and impact, as the data falsification
concerns, which were discovered at Ranbaxy (Katherine Eban’s stunning investigation in Fortune, “Dirty Medicine” covers this extensively). One of the main promoters of GVK Biosciences is Mr. D.S. Brar who was CEO & Managing Director of Ranbaxy from 1999-2004. The impact of GVK
Biosciences’ misdeeds is already being felt on new product launches. Mylan recently withdrew its European application for generic
Abilify (aripiprazole) (2014 sales US$6.2x billion) citing “identification of major GCP issues (Good
Clinical Practices).” What about the impact on the US market?In 2010, FDA discovered data integrity
violations, which bankrupted
clinical research organization, Cetero Research/PRACS. Based on the Cetero findings
in the United States, the EMA suspended seven drugs. Now it remains to
be seen, how the FDA will handle the data integrity concerns found in Europe
since products like repaglinide & candesartan cilexitil (Mylan), levetiracetam (Dr. Reddy’s), clonazepam (Sandoz), metformin hydrochloride (Actavis), tacrolimus (Panacea Biotech) all have U.S. FDA approvals. Leading GVK Biosciences’ defense is the Indian government, who warned last month that if the European Union does not reconsider their decision, it may go to the World Trade Organization. The Indian government’s position is based on an appeal by GVK Biosciences, which made the “Indian government set up a panel of experts last year to investigate
the matter and found no manipulation”, GVK Biosciences CEO Manni Kantipudi told Reuters.However, globally reputed GMP expert, Lachman Consultants, believes that the GVK Bioscience episode “could potentially impact data integrity, similar to the Cetero/PRACS
case”.It’s clear for us that this is not the end of the story…
Impressions: 4076
https://www.pharmacompass.com/radio-compass-blog/will-data-integrity-concerns-on-clinical-trials-done-at-gvk-biosciences-go-beyond-europe
#PharmaFlow by PHARMACOMPASS
28 May 2015
