This week, we go back to the controversies spiked by the FDA’s approval of Biogen’s Aduhelm drug that tackles Alzheimer’s disease. We discuss the FDA documents that showed the split of the organization and look at the criticism following Biogen’s announcement of the annual price for the drug. We also take a look at the prostate cancer drug that shows promising results in improving the Covid-19 survival according to the preliminary trial, GSK turning its consumer healthcare arm into a separate listed entity, the largest-ever Series A in France, and the newest antibody study in the US that shows that millions of Covid-19 cases went undetected and the virus was present in the country long before anybody could expect it.
Controversial Approval Of The Alzheimer’s Drug: FDA Releases Documents That Shows Behind The Scenes Of The Biogen’s Aduhelm Decision
Last week, we have been writing about the FDA approval of Biogen’s Alzheimer’s drug that was controversial to many experts pointing out that without any clear proof the therapy is working, Biogen will be able to capitalize on a drug for several years while more research is being conducted. Now, the FDA has released documents that show the steps leading to the approval of the Alzheimer’s drug Aduhelm. The documents show that the agency was truly divided trying to decide whether the drug should be granted approval.
Although the first meetings occurred already in November of 2020, the culmination happened on the April 26 meeting. Crucially, Patrizia Cavazzoni, M.D., Peter Marks, M.D., Ph.D., and Richard Pazdur, M.D.—respectively, the directors of the FDA’s centers for drug evaluation, biologics evaluation and the oncology center of excellence—voiced support for accelerated approval. Although Pazdor holds experience in accelerated approval, his specialty is not neuroscience.
The proposal was opposed for example by Sylva Collins, Ph.D., director of the Office of Biostatistics. Collins claimed that the evidence present is not enough to support accelerated approval or any other type of approval for Biogen’s Aduhelm.
Tristan Massie, Ph.D., a mathematical statistician at the FDA, said the “whole pattern of study outcomes could be explained by a randomly worsened placebo after the dose increase amendment,” adding that there is “compellingly conflicting phase 3 evidence,” and approval “would likely present challenges to other Alzheimer’s candidates in development.” Massie recommended against approval.
In the end, the concerns by Massie and Collins were overpowered by the support of other members and the drug got its accelerated approval. However, it remains controversial and many experts in the field keep debating whether the approval was not a mistake.
Yesterday, The U.S. National Institutes of Health (NIH) announced it has started to study the immune responses generated by the different Covid-19 vaccines in pregnant and postpartum women. Pregnant women are at higher risk of complications including premature birth, high blood pressure with organ failure risk, need for intensive care, and possible death, according to the NIH.
There was already a small-scale study conducted back in February in Israel. Back then, it was shown that antibodies were present in all 20 women that received both doses of the Pfizer/BioNTech vaccine during the last trimester of pregnancy and also in newborns. Apart from this, there was a separate study that Pfizer has conducted with 4000 international pregnant women.
The NIH study, MOMI-VAX, will measure the development and durability of antibodies against the coronavirus in women vaccinated during pregnancy or the first two postpartum months. The researchers will focus on safety but also to what degree women are passing the protection to the virus via placenta or breast milk.
“The results of this study will fill gaps in our knowledge and help inform policy recommendations and personal decision-making on COVID-19 vaccination during pregnancy,” National Institute of Allergy and Infectious Diseases Director (NIAID) Dr. Anthony Fauci said.
1000 women total will be enrolled in the trial that will be financed by NIAID. 750 women will be pregnant with another 250 postpartum (within two months of delivery).
The latest clinical trial showed that an experimental prostate cancer drug improved the survival of hospitalized Covid-19 patients. The drug, proxalutamide being developed by Kintor Pharmaceuticals, blocks the effects of androgen hormones by inactivating their “receptors” on cell surfaces.
The co-author of the study, John Mccoy of Applied Biology Inc explained, “ Before the spikes on the surface of the coronavirus can break into cells and infect them, they must be “primed” by a protein called TMPRSS2, which is regulated by androgen receptors”
In the Brazil trial, 645 patients received either proxalutamide for 14 days or a placebo, plus standard care. After two weeks, recovery rates were 81.4% for the proxalutamide group versus 35.7% for those who got a placebo. After four weeks, 49.4% in the placebo group had died, versus 11% with proxalutamide. Although women are generally not expected to respond to drugs that block male hormones, the benefits of the drug were similar across sexes.
Yesterday, GSK announced it plans to turn its consummate healthcare business into separately listed companies, as it is expected to deliver a windfall of $11 billion, as well as a series of other financial benefits for its underperforming drugs business.
The split is expected to happen in Q3 of 2022 and will give GSK the chance to focus on its core drugs and vaccine business that has lately suffered because of no fast-growing products. During the pandemic, the GSK (which is the biggest vaccine maker, by sales, in the world) has been outperformed by Pfizer, Moderna, and AstraZeneca.
“I am very aware that GSK shares have underperformed for a long period,” CEO Emma Walmsley told a news conference, adding she would stay at the helm of the pharma and vaccines business called New GSK. “Together, we are now ready to deliver a step-change in growth for New GSK and unlock the value of Consumer Healthcare,”
GSK is currently valued at about 10.3 times its forecast core earnings, including net debt, below an average of more than 12 for global pharma majors, Refinitiv Eikon data shows. According to the forecast, the pharmaceuticals business could increase the sales by over 5% annually. GSK announced it wants to sell a residual 20% stake in the newly listed consumer business “in a timely manner”.
“We see the key positive for the market today being a smaller dividend cut than feared, we see the key negative for the market is the 20% sale of the Consumer stake, which will dilute GSK shareholders exposure to this segment, and which could see some value going to the taxman. The 2031 Biopharma Revenue target of more than 33 billion pounds ($46 billion)is far above our expectations,” the JPMorgan analyst said. “Given fairly low expectations heading into today’s update, we believe shares could see slight outperformance on the smaller than feared dividend cut, and increased clarity on company expectations. For further outperformance, we will need to understand how GSK plan to get to their ambitious 2031 Revenue target, in particular, how they will navigate the dolutegravir patient expiry in 2028.”
“GSK’s announcement contained a whole host of market-friendly targets, including a welcome target for double-digit profit growth over the next five years that will need to be underpinned by a belief in the products in development and the segments the company will be focusing on,” said Chris Beckett, head of equity research at investment firm Quilter Cheviot. “It will not be a completely clean break from the new consumer business. The rationale for ongoing investment in the consumer business will need to be explained by the executives. Investors won’t appreciate the overhang.”
The biotech company, Mnemo Therapeutics, has just raised €75M in what was the largest-ever French Series A round. The startup will use the fresh funding to develop CAR T-cell immunotherapies for cancer using epigenetic targets. Epigenetics is based on very small and reversible modifications to DNA molecules that change the way genes are expressed without altering the genetic code itself.
The round was led by Casdin Capital, with the participation of a returning investor Sofinnova Partners, and an undisclosed investor. “The goal is to be IND- and phase I-ready by the end of 2023 for at least two projects,” said Alain Maiore, CEO of Mnemo Therapeutics.
“Advances in epigenomic capabilities will bring forward the next wave of innovation in cancer development through the discovery and development of novel small molecules,” stated Susan Galbraith, AstraZeneca’s Senior Vice President and Head of Research and Early Development, Oncology R&D. “Proteros’ proprietary discovery platform enables us to screen epigenetic targets in a physiologically relevant setting, supporting accelerated discovery and development of the next wave of anti-cancer medicines,” she added.
There are several other companies that are leveraging epigenetics and several drugs that have already been approved by the regulators that treat cancer by the user of epigenetics.
“What is different [with Mnemo Therapeutics] is that we are knocking out a particular epigenetic regulator in CAR-T cells to increase their persistence, which we know is important for greater efficacy in patients,” Maiore explained.
FDA Latest Approval Of Biogen’s Alzheimer’s Drug Raises Questions Of Who Will Be Able To Afford It
FDA’s approval of Biogen’s drug for Alzheimer’s raises controversies not only about its effectiveness and the possibility to capitalize on a drug that may not be effective but also the affordability of the drug. Biogen has set the average price for Aduhelm at $56,000 per year which is severely higher than what many people have expected.
According to The Wall Street Journal, Cigna, one of the nation’s largest health insurers, estimates some eligible patients may end up paying at least $10,000 from their own pockets. The high price is causing even more discussions as many institutions including The Institute for Clinical and Economic Review, a prominent watchdog group for drug pricing, went out to publicly criticize not only the price set by Biogen but the FDA itself for approving the Alzheimer’s drug with practically no limitations.
“Alzheimer’s disease has a tremendous impact on patients and loved ones, and no one can be insensitive to the hopes and the fears that are part of their daily lives,” ICER said in a statement. “But no one should assume that approving a drug with such conflicting and uncertain evidence will necessarily help patients and families.”
However, Biogen’s executives keep defending the price. “We believe that this price is really fair,” said Chirfi Guindo, head of global product strategy and commercialization, in an interview. “It is sustainable and we remain open-minded.”
More On The FDA Controversy Regarding The Alzheimer’s Drug Approval:
The new antibody study by the National Institutes of Health shows that millions of Covid-19 cases could be missed and not be counted into the official count. According to the researchers’ estimates, in the spring and summer of 2020 alone, every infection caught was followed by undiagnosed 4.8 infections. That would add 16.8 million new Covid-19 cases only by July of 2020.
The study is building on the relatively new evidence from the NIH illustrating that Covid-19 was present in the US long before it was considered as an emergency, as early as December 2019. As the scientists now use archived blood samples, antibody studies show a much clearer picture of how the disease could be spreading across the country without being detected.
“This study helps account for how quickly the virus spread to all corners of the country and the globe,” Bruce Tromberg, director of the NIH’s National Institute of Biomedical Imaging and Bioengineering, said in a statement. “The information will be invaluable as we assess the best public health measures needed to keep people safe, as new—and even more transmissible—variants emerge and vaccine antibody response changes over time.”
At first, 240 000 volunteers were recruited. Then, roughly 8000 people were selected as a sample to ensure the analysis was representative of the U.S. population. Every participant either sent a deb of their dried blood or had blood drawn at one of the NIH clinics, with most specimens coming in between May and July 2020. The results were published in Science Translational Medicine.
“The estimate of COVID-19 cases in the United States in mid-July 2020, 3 million in a population of 330 million, should be revised upwards by almost 20 million when the percent of asymptomatic positive results is included,” said the study’s senior co-author, Kaitlyn Sadtler, chief of the NIBIB section on immune engineering.
“This wide gap between the known cases at the time and these asymptomatic infections has implications not only for retrospectively understanding this pandemic but future pandemic preparedness,” Sadtler said.