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AstraZeneca’s vaccine, Gilead’s remdesivir stumble; FDA finds water leakages from ceiling at Aurobindo’s US facility
This week, Phispers brings you more updates on Covid vaccines and therapies. While Pfizer-BioNTech submitted their vaccine candidate for an emergency use authorization (EUA) to the FDA, Oxford-AstraZeneca announced efficacy results of their vaccine.
The FDA granted EUA to Eli Lilly’s arthritis drug, baricitinib, in combination with Gilead’s remdesivir, to treat Covid-19 patients. Regeneron’s antibody cocktail (casirivimab and imdevimab) for Covid-19 also received an EUA from the FDA.
However, remdesivir received a major setback from the WHO, as one of its panels advised against the use of the drug in hospitalized patients. Merck, on the other hand, strengthened its portfolio of Covid-19 drugs by buying biopharmaceutical company OncoImmune for US$ 425 million.
In regulatory news, the FDA issued a warning letter to Aurobindo’s US facility where it uncovered multiple compliance concerns including instances of water leakages in critical operation areas. And Trump announced two new rules to slash drug prices that will come into effect on January 1.
‘Dosing error’ pushes Oxford-AstraZeneca vaccine’s efficacy to 70 percent
After Pfizer-BioNTech and Moderna posted their vaccine efficacy results that exceeded expectations, AstraZeneca-Oxford announced efficacy of its vaccine, AZD1222. After going through AstraZeneca’s statement and various news reports, we find the data rather disappointing with an average efficacy of 70 percent. However, one dosing regimen (sample size, or n=2,741) showed vaccine efficacy of 90 percent when AZD1222 was given as a half dose, followed by a full dose at least one month apart.
Another dosing regimen (n=8,895) showed an efficacy rate of only 62 percent when given as two full doses at least one month apart. The combined analysis from both dosing regimens (n=11,636) resulted in an average efficacy of 70 percent.
“The reason we had the half-dose is serendipity,” Mene Pangalos, head of AstraZeneca’s non-oncology research and development, told Reuters. Due to this ‘dosing error’, the vaccine could be around 90 percent effective when administered as a half dose followed by a full dose a month later, AstraZeneca said.
The biggest advantage of the Oxford-AstraZeneca vaccine is the fact that it is cheaper and easier to distribute than the shots developed by Moderna and Pfizer. Vaccines from Pfizer and Moderna may have proven to be 95 percent effective, but they need to be frozen during distribution and kept at very cold temperatures. In contrast, AstraZeneca’s vaccine can be transported and stored under refrigerated conditions for at least six months.
The British drugmaker will submit preliminary data from large clinical trials in the UK and Brazil to the FDA as part of an application for emergency authorization. The company will also seek an emergency use listing from the World Health Organization (WHO) as a quicker way of making the vaccine available in low-income countries.
WHO panel advises against use of Gilead’s remdesivir in hospitalized patients
Last month, the World Health Organization (WHO) led Solidarity trial had said that Gilead’s remdesivir had little or no effect on the 28-day mortality or length of hospital stays for Covid-19 patients. A week after this news, the US Food and Drug Administration (FDA) approved remdesivir for hospitalized patients.
In yet another setback to Gilead’s remdesivir, the WHO’s Guideline Development Group has said the drug should not be used for patients hospitalized with Covid-19, regardless of how ill they are, since there is no evidence that the drug improves survival or reduces the need for ventilation.
In fact, the WHO has suspended remdesivir from its so-called pre-qualification list, an official list of medicines used as a benchmark for procurement by developing countries.
In a statement, Gilead said it is “disappointed” with the WHO guideline, as it ignores other studies. Remdesivir is approved for use as a Covid-19 treatment in more than 50 countries.
The European Medicines Agency (EMA) has requested the full Solidarity data from the WHO and the marketing authorization holder. Once the data is available, it will see if any changes are required to the marketing authorization of Veklury (remdesivir) in the EU, the EMA said in a statement.
Meanwhile, the Infectious Diseases Society of America (IDSA) has said remdesivir should be used for hospitalized Covid-19 patients despite the WHO’s recommendation.
After favorable results from Phase 3 trials, Pfizer submits vaccine for EUA to the FDA
After sharing favorable results from a completed phase 3 clinical trial, Pfizer and BioNTech have submitted an emergency use authorization (EUA) application to the US Food and Drug Administration (FDA).
The FDA has set December 10 as the date for the Vaccines and Related Biological Products Advisory Committee to review the EUA request. The messenger RNA vaccine developed by Pfizer and BioNTech has demonstrated 95 percent efficacy.
“It is with great pride and joy – and even a little relief – that I can say that our request for emergency use authorization for our Covid-19 vaccine is now in the FDA’s hands,” said Pfizer’s CEO, Albert Bourla. The vaccine is already under rolling review in Europe, Japan, Australia, and Canada, he added.
Pfizer and BioNTech expect the FDA to grant the EUA by mid-December. Bourla said that Pfizer and BioNTech will be prepared to produce up to 50 million doses globally in 2020, and up to 1.3 billion by the end of 2021.
In the UK, Pfizer-BioNTech are likely to bag an approval soon. “It is our job now to rigorously assess these data and the evidence submitted on the vaccine’s safety, quality and effectiveness,” June Raine, CEO of Britain’s Medicines and Healthcare products Regulatory Agency said.
Merck buys OncoImmune for US$ 425 million to strengthen Covid-19 portfolio
Merck has been building its portfolio of Covid-19 medicines through a series of deals in recent months, including the acquisition of Australian drugmaker Themis and a partnership with Ridgeback Biotherapeutics. This week, there is news that Merck is acquiring privately-held biopharmaceutical company OncoImmune for US$ 425 million. The deal will give Merck control of CD24F, a therapeutic candidate in phase 3 trials for Covid-19.
With these recent acquisitions, Merck has two Covid-19 vaccines in the clinic, albeit at an earlier stage than rival candidates, and an antiviral in phase 2/3 development.
The therapy CD24F, which is administered as an injection, increased the likelihood of symptom improvement in serious Covid-19 cases and also reduced the risk of respiratory failure and death, said Roger Perlmutter, who heads research at Merck.
Perlmutter said CD24F could potentially complement dexamethasone, a generic steroid that is the current standard of care for the most serious Covid-19 cases. Merck is aiming to develop the manufacturing capacity needed to produce the therapy.
Before bidding adieu, Trump announces new rules to lower Medicare drug prices
Friday, November 20, was the last day the Trump administration could release a rule which would then be finalized in the 60 days before Inauguration Day. And the US President Donald Trump didn’t forego that opportunity.
In a last-ditch bid to deliver on his 2016 campaign promise to slash drug prices, Trump unveiled two plans on November 20 — one, he would be instituting the “most favored nations” (MFN) rule, tying prices in the US to those in other developed countries; and two, he would be ending certain rebates paid to middlemen, also known as pharmacy benefit managers, in Medicare.
The two rules were a part of four executive orders unveiled in July. Trump said the rules will begin to take effect on January 1 and are slated to run for the next seven years.
Trump also accused Pfizer “and others” of delaying vaccine trial results for political reasons. “The drug companies don’t like me too much, but we had to do it,” he said.
Experts said the rules are unlikely to survive legal challenges since the Trump administration had circumvented critical parts of the rule-making process to get them finalized before President-elect Joe Biden assumes office. It is not clear if the incoming Biden administration will keep the rules.
Criticizing the new rule, drug industry lobby group Pharmaceutical Research and Manufacturers of America’s (PhRMA) president and CEO, Stephen Ubl, said in a statement: “It defies logic that the administration is blindly proceeding with a ‘most favored nation’ policy that gives foreign governments the upper hand in deciding the value of medicines in the United States.”
FDA grants EUA to Lilly’s arthritis drug, in combination with remdesivir, to treat Covid
Last week, the US Food and Drug Administration (FDA) approved emergency use of Eli Lilly’s arthritis drug, baricitinib, in combination with Gilead’s remdesivir, to treat Covid-19 patients. Sold under the brand name of Olumiant, baricitinib is an FDA-approved oral medication used to treat moderate-to-severely active rheumatoid arthritis.
The approval was based on a review of the data from a clinical trial of hospitalized Covid-19 patients. The trial showed around a one-day reduction in median recovery time for patients treated with the combination versus those treated with remdesivir.
Regeneron’s antibody cocktail also bags EUA: Regeneron Pharmaceuticals has also announced that their antibody cocktail, casirivimab and imdevimab administered together as a therapy for use in Covid-19, has received emergency use authorization (EUA) from the FDA.
The antibody cocktail is authorized for the treatment of mild to moderate Covid-19 in adults, as well as in pediatric patients at least 12 years of age and weighing at least 40 kg, who have received positive results of direct SARS-CoV-2 viral testing and are at high risk for progressing towards severe Covid-19 and/or hospitalization.
The casirivimab and imdevimab combination therapy continues to be evaluated in Phase 2/3 clinical trials for the treatment of Covid-19. To date, more than 7,000 people have participated in the casirivimab and imdevimab clinical trials.
FDA issues warning letter to Aurobindo’s US facility
The US Food and Drug Administration (FDA) posted a warning letter issued to Aurolife Pharma, a subsidiary of Indian drugmaker Aurobindo Pharma, on its website. Aurolife’s New Jersey unit was inspected by the FDA from January 13 to February 12, 2020. The warning letter has summarized significant violations of current good manufacturing practice (CGMP) regulations for finished drugs.
Significantly, the inspection uncovered multiple incidences of water leakage from the ceiling into the facility’s encapsulation and packaging rooms.
The warning letter highlights that in 2018 there were four incidences of water leakage from the ceiling of the encapsulation room which exposed multiple batches of Gabapentin capsules, USP 100 mg, to these leaks. The New Jersey facility also experienced water leaks during the encapsulation operations of phentermine capsules.
In addition, there were at least five instances of water leaks in the packaging area and some of these occurred while tablets were being filled into open containers. The FDA inspectors found that Aurolife failed to ensure that the root cause of these leaks was addressed promptly. It also did not adequately assess the risks due to exposure of products to elevated ambient moisture.
During the inspection, FDA investigators also observed surfaces covered in powder throughout the facility including API sampling rooms, raw material dispensing rooms, common production corridor areas, granulation rooms, and compression rooms.
Aurolife was also found to invalidate initial out-of-specification (OOS) impurity testing results for olanzapine active pharmaceutical ingredient (API) and finished drug product without sufficient investigation to determine the root cause of the failures.
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