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5 FDA approval decisions to watch in the second quarter

photo: Jacob Bell

The Food and Drug Administration doesn’t yet have a new full-time commissioner. But whoever fills the seat in the coming months — be it acting chief Janet Woodcock or another candidate — could start the job with some tough decisions to make.

At the top of the list is whether the agency should clear an experimental Alzheimer’s drug from Biogen. That decision is among the most consequential the FDA has ever faced, as an approval or rejection will have ripple effects on Alzheimer’s research, the agency’s reputation and the biotech sector for years to come.

But there are other consequential verdicts expected as well. The agency will likely soon begin reviewing a coronavirus vaccine from AstraZeneca that has been the subject of an unusual public dispute between the drugmaker and its independent trial review board.

Within the next three months the FDA could also change the standard of care for a rare genetic disease and clear a new vaccine for one of the world’s most common infections.

Any rejection could add to an impression that the FDA is becoming stricter of late, after a series of surprising regulatory knockbacks and an industry-wide evaluation of cancer immunotherapy approvals. Clearance of Biogen’s drug, meanwhile, would have the opposite effect.

Editor’s note: The following five drugs are listed in order of the date by which the FDA is expected to make a decision on approval.

Pimavanserin is a critical asset for Acadia Pharmaceuticals. The company’s only product, it’s been on the market for several years, sold under the brand name Nuplazid for the treatment of Parkinson’s disease psychosis. In 2020, net sales of Nuplazid rose 30%.

Acadia has been trying to stoke further growth by getting its drug cleared for use in more diseases. Last year, the company asked the FDA for an approval in dementia-related psychosis, with a decision date set for April 3.

Acadia executives thought the outlook for approval was good. That was, until a few weeks ago, when they disclosed that regulators found “deficiencies” in the company’s application. According to Acadia, the deficiencies prevent the FDA from discussing marketing requirements at this time.

“We were extremely surprised and disappointed to receive such a communication from the FDA, and to receive it so late in the review cycle,” Steve Davis, Acadia’s CEO, said during a call with investors this month.

While not yet an official rejection, the agency’s feedback seems to have ruled out an April approval and lowered the chance of an eventual OK. Vamil Divan, an analyst at Mizuho Securities, wrote in a recent note to clients that his team believes the odds are at 60%, versus 70% previously. They also expect the drug’s launch in dementia-related psychosis to be pushed back multiple years, to 2024.

AstraZeneca and Oxford’s coronavirus vaccine

The three coronavirus vaccines available for use in the U.S. were cleared by the FDA without much drama. But that likely won’t be the case for the fourth potential shot, from AstraZeneca and the University of Oxford.

AstraZeneca’s shot appears headed towards a review in April. A series of communication missteps and safety setbacks, however, have damaged the company’s credibility as well as public perception of the shot.

Positive but confusing data from earlier studies in the U.K. and elsewhere left it unclear how to best use the shot or whether it worked as well in the elderly. A trial stoppage of almost two months, meanwhile, delayed AstraZeneca’s larger trial in the U.S. and South America. And more recently, rare, abnormal blood clots have occurred during the shot’s roll-out in Europe, leading a large number of countries to temporarily suspend vaccinations. Some have since resumed administration.

Last week, Astrazeneca reported the shot was safe and strongly effective at preventing COVID-19 in the U.S. study, clearing a major test and setting the stage for the FDA’s review. But the good news was shadowed by controversy. The board of independent experts overseeing the trial publicly disputed the initial results the drugmaker released — an unusual and stunning rebuke.

The advisory meeting to discuss the shot, which could take place next month, will likely reflect those twists and turns. Briefing documents outlining the FDA’s own findings could shed light on the disagreement between AstraZeneca and its data monitoring board. And the meeting will give scientific experts a chance to question AstraZeneca executives on that topic and several other outstanding questions.

Sanofi’s avalglucosidase alfa for Pompe disease

People with Pompe disease have a genetic mutation that stops their bodies from producing a key enzyme that breaks down a complex sugar called glycogen. The resulting buildup of glycogen causes progressive tissue damage and other health problems.

For years, the main treatment for Pompe has been chronic treatment with a so-called enzyme replacement therapy, called Lumizyme, that Sanofi acquired when it bought rare disease drug developer Genzyme ten years ago. But the French pharmaceutical giant aims to set a new treatment standard by winning approval of a successor therapy called avalglucosidase alfa. The new treatment is meant to deliver more of the enzyme into cells, improving potency.

The company has yet to prove that hypothesis, however. In a Phase 3 study, avalglucosidase alfa matched Lumizyme as measured by improvements in respiratory function, the main goal of the trial. The “clinical relevance” of the difference between how the two drugs work hasn’t been established yet, the company said.

Still, approval of Sanofi’s new drug could raise the bar for a number of other treatments in development, among them a pill from Amicus Therapeutics and gene therapies from Roche, Bayer and Avrobio.

A decision is expected by May 18.

Biogen’s aducanumab for Alzheimer’s disease

Despite extensive research efforts, Alzheimer’s disease remains one of the most challenging areas of drug development. Promising therapies have failed time and again, leaving patients with only a small crop of treatments to combat their symptoms, rather than the disease itself.

But the options for treatment could change soon. The FDA should decide by June 7 whether to approve Biogen’s aducanumab, which many consider the most closely watched drug in all of biotech. A nod from regulators would make aducanumab the first marketed drug meant to slow the progression of Alzheimer’s — a title that Wall Street analysts expect to translate to billions of dollars in annual sales.

An approval is far from certain, however. The FDA’s own statisticians, as well as an external group of advisors, have criticized the aducanumab data and the ways in which Biogen analyzed it. In a November meeting, those advisors voted almost unanimously against the drug. Though the FDA isn’t required to follow these recommendations, it typically does.

Still, analysts haven’t written off aducanumab. Not only is the FDA under immense pressure to get more Alzheimer’s drugs to patients, but the agency’s clinical staff have been uncharacteristically supportive of Biogen’s application.

When regulators recently decided to extend their review of aducanumab, some took it as a sign they’re combing over more data that could support an approval. Evercore ISI analyst Umer Raffat had told BioPharma Dive that an extended review would bump his estimate for the probability of approval from below 50% up to 70%. The investment bank Stifel, meanwhile, has forecasted a 60% chance of approval.

Pfizer’s 20-valent pneumococcal vaccine

Two companies, Pfizer and Merck & Co., have approved vaccines to prevent pneumococcal disease. Neither of those vaccines, however, protect against key emerging strains of the infectious bacteria. And that’s why both are locked in a race to get the next generation of shots onto the market. That race could reach its conclusion this year.

Pfizer is in the lead with its experimental vaccine that stimulates immunity to 20 different strains of disease-causing bacteria.

The new product protects against the same 13 serotypes that the current standard, Prevnar 13, does, plus seven more that have been associated with higher death rates, antibiotic resistance or meningitis. At nearly $6 billion in 2020 sales, Prevnar 13 was Pfizer’s single-biggest product, but the shot will lose patent protection in 2026.

The new vaccine could help the franchise going for Pfizer. By June, the FDA will decide whether to approve Pfizer’s 20-valent shot for use in people 18 years and older. That’s a smaller population than is authorized for Prevnar, which can be used in children and infants as young as six weeks. But Pfizer aims to eventually treat that group as well, having already published Phase 2 data for the new vaccine in infants and children.

Merck is close behind, with a decision due July 18 for its 15-valent pneumococcal vaccine called V114 in adults 18 and older. V114 is designed to follow the company’s older 23-valent shot called Pneumovax 23 and like Pfizer’s new product protects against key strains that are helping drive disease.

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