AV-COVID-19

With little explanation for why Merck’s potential Covid-19 antiviral was less effective in reducing Covid hospitalizations and deaths in a full analysis of a Phase III trial versus an interim look, the FDA’s antimicrobial drugs advisory committee on Tuesday voted 13-10 in favor of the pill’s benefits outweighing the risks for adults within 5 days of developing Covid symptoms. Molnupiravir will likely be authorized by FDA in the coming days for adults with mild or moderate Covid-19. While Pfizer’s antiviral may prove to be more effective, Merck’s pill will be another weapon in the armamentarium of Covid-19 treatments for countries around the world, adding to the mAb treatments already in use in the outpatient space from Regeneron, Eli Lilly and Vir/GlaxoSmithKline. Adcomm member David Hardy of the Charles Drew University School of Medicine and Science said he voted “yes” because the pandemic is still an emergency situation, and this is the first opportunity for an oral drug to be available. There needs to be a warning about using this drug in pregnant women, he said, noting of the potential for fetal abnormalities. Panelist Timothy Burgess of the Uniformed Services University of the Health Sciences said he voted “no” on the basis of the very difficult to explain differences in the population before and after the interim analysis (see below), and the heterogeneity of the benefit, particularly for those with diabetes. During the discussion portion of the adcomm, panelists centered their questioning on the Merck pill’s efficacy and the cause of this drop off in preventing hospitalizations and deaths, from 50% to 30% between interim and final results. Neither Merck nor the FDA could really offer any specific causes. Subgroup analyses seem to suggest that molnupiravir did better against the Gamma and Mu variants than the Delta variant, but that doesn’t explain how steeply the efficacy fell. For instance, in the post-interim analysis population, FDA showed how there were more Covid-related hospitalizations among trial participants receiving molnupiravir compared to those receiving placebo. “It doesn’t really add up to us,” Nicholas Kartsonis, SVP of clinical research, infectious diseases at Merck, said. He noted that the company expected some regression to the mean with the later data, but not this kind of reduction in benefit. He pointed to several potential factors, including the rise of Delta, more female trial participants who are less likely than their male counterparts to be hospitalized or die of Covid, and more participants in Europe in the second part of the trial. “I don’t have a satisfying answer but that’s the totality of data,” Kartsonis said. When FDA sought to direct the conversation to questions about the efficacy of molnupiravir in pregnant women, several panelists also questioned the efficacy in adults in general. “We’re skirting the issue of is there a benefit of the medication in adults,” said adcomm panelist Uma Reddy, who’s an OBGYN at Yale. Panelist Michael Green, professor of the University of Pittsburgh School of Medicine, voted in favor of the pill’s benefits and noted the lack of availability of an alternative oral treatment for unvaccinated people, and the potential loss of mAbs due to the new variant Omicron, which Merck said it thinks the antiviral will be effective against. “Should an alternative oral drug with a better safety profile, the agency might consider this authorization,” Green said. Another issue for the adcomm members is the way that molnupiravir works, which is to drive the mutagenesis of the SARS-COV-2 virus to kill it off, and which could theoretically increase the likelihood of variants occurring as a result of widespread treatment. But the FDA noted in its presentation that there’s no evidence that the emergence of spike protein amino acid changes affected virologic or clinical outcomes in outpatients. Kartsonis said Merck will be strongly recommending that people complete their 5-day treatment courses to avoid any theoretical concerns. “We are exploring the feasibility of using sequence databases to monitor for the emergence of these novel variants,” Kartsonis added. “To date, if you treat people for 5 days, we’ve yet to identify a single case of infectious virus at day 5, so that’s a very positive sign.” Several panelists also said they thought the risk for the general public is low compared to the substantial amount of natural mutations, but a few did raise concerns, particularly if millions of people access the drug. The overall thumbs up from the panel is based on results from a Phase III trial of about 1,500 unvaccinated adults, finding 68 hospitalizations and 9 deaths in the placebo group, compared to 48 hospitalizations and one death for those on the Merck pill. The FDA said in its analysis of Merck’s data that the pill is safe and reduces the risk of hospitalization or death among adults with mild to moderate Covid-19 and who are at high-risk for progression to severe Covid. Similar to the UK, the FDA is not likely to recommend the pill for pregnant women due to the potential of embryo-fetal toxicity. The US has now purchased more than 3 million courses of the Covid-19 antiviral, to be acquired from authorization through early 2022, Merck said. The contracts have earned Merck a cool $2.2 billion so far, and there are two million courses available through further options.

Mike Kemp/In PIctures via Getty Images The J.P. Morgan Healthcare Conference kicked off with a different look this year, a virtual platform due to the ongoing COVID-19 pandemic. Instead of the hustle and bustle of navigating hotel halls in San Francisco, pharma executives and investors only had to navigate Zoom calls and online presentations. BioSpace takes a look at some of the announcements that occurred Monday and will continue to update throughout the week. BioNTech’s Big Bet – The past year has been a good one for Germany-based BioNTech. The company quickly developed a vaccine for the novel coronavirus and then partnered with Pfizer to develop the medication. Pfizer and BioNTech’s mRNA vaccine, BNT162b2 demonstrated a 95% efficacy in clinical trials and has since received authorization for use in the United States, Europe and the United Kingdom. During a Monday presentation at J.P. Morgan, BioNTech Chief Executive Officer Ugur Sahin announced an aggressive vaccine manufacturing plan for the rest of the year. Sahin said the company intends to supply up to 2 billion doses of the vaccine by the end of the year. Manufacturing efforts will be supported by three U.S. based facilities, one in St. Louis, one in Kalamazoo, Michigan and one in Andover, Michigan. Three European facilities will also support ramped up manufacturing efforts for the mRNA vaccine, Sahin said. While COVID-19 is the infectious disease of the moment, Sahin said it’s not the only threat in the world. Infectious diseases represent a long-term growth pillar for BioNTech and many of them do not have available vaccines or therapies. The company will use its mRNA technology to develop vaccines for HIV, influenza and tuberculosis. Takeda’s Financial Goals – Over the course of the next decade, Takeda Pharmaceutical has a goal of reaching $47 billion in annual revenue by 2030. That financial goal represents a 50% growth from 2019, the company said at the conference. CEO Christophe Weber said the company’s externally-facing R&D engine has generated an innovative and modality diverse pipeline of approximately 40 clinical-stage new molecular entities (NMEs) that will help Takeda reach that lofty financial goal. The majority of revenue growth is expected to come from the company’s Wave 1 pipeline, which includes 12 unique NMEs, representing potential best-in-class/first-in-class therapies and its existing 14 global brands, the company said. That Wave 1 program includes five pipeline assets that have received Breakthrough Therapy designation and three that have been granted Fast Track designation by the U.S. Food and Drug Administration. Twelve pivotal milestones, including five pivotal data readouts, are expected through fiscal year 2022 with additional near-term development milestones expected across all Wave 1 programs, the company said. Assets in the Wave 1 pipeline include TAK-003, the company’s tetravalent dengue vaccine candidate. Dengue is the fastest spreading mosquito-borne viral disease and was recognized by WHO to be one of the top ten threats to global health in 2019. Also in Wave 1 is TAK-755, a potentially transformative therapy for thrombotic thrombocytopenic purpura (TTP), a rare and life-threatening clotting disorder. Updated 2020 Guidance – Gilead Sciences made waves in 2020 with the only COVID-19 antiviral to receive full approval from the FDA. On Monday, the company revised its guidance for 2020 to $24.30 billion to $24.35 billion, which was largely driven by the ongoing COVID-19 pandemic. Increased hospitalizations due to the virus have meant more people are receiving Veklury (remdesivir). CEO Stephen O’Day said use of Veklury has jumped from about 30% in October to nearly 60% due to the spike of COVID-19 cases. A Multi-Franchise Portfolio – Biogen CEO Michel Vounatsos said the Boston-based biotech’s goal is to build on its multiple sclerosis, spinal muscular atrophy and biosimilars businesses to diversify into a multi-franchise portfolio. Vounatsos said the company has made significant progress delivering on this strategy and expects “significant regulatory and clinical milestones” in 2021. He predicted this year will be transformative for Biogen. “Importantly, we have enhanced our pipeline by increasing the number of disease areas. We are targeting leveraging the interconnectivity neuroscience, including new programs with genetically validated targets, new modalities and new biosimilars,” Vounatsos said, according to a transcript. Biogen is waiting with bated breath for the potential approval of its Alzheimer’s disease treatment, aducanumab. Vounatsos said he is confident in the clinical pro aducanumab in Alzheimer’s and believes the data supports approval. In addition to aducanumab, Biogen is also advancing BAN240 and BAN241. Accelerated Growth – Regeneron is looking at a period of accelerated growth due to several anticipated launches, the company said Monday. CEO Leonard Schleifer said the strength of the company’s core products, a wave of new launches, and a broad pipeline positions Regeneron for “continued and frankly for accelerating growth.” Schleifer said there is continued market growth for its Eylea business and noted that Dupixent, which iy has partnered with Sanofi on, is “transforming the treatment of type 2 inflammatory diseases.” Immuno-oncology is also predicted to be a driver for the company. Regeneron’s Libtayo was the first approved anti-PD-1 in cutaneous squamous cell carcinoma, and Schleifer said there are more indications coming for the drug. “We've got priority review in second line, BCC (basal cell carcinoma) as well as priority review in non-small cell lung cancer. That priority review is important, because we think it reflects the fact that we have some differentiation in terms of the patient population that we studied. And frankly, we think of Libtayo as potentially best-in-class and we'll have to see how it all plays out,” Schleifer said during the presentation. Most Read Today