The Food and Drug Administration has a lot on its plate over the next three months.
The agency may soon issue a decision that could greatly boost access to an Alzheimer’s medicine that’s been hampered by a strict Medicare coverage policy. The regulator could also clear a new type of depression drug and another option against a common respiratory infection. Two advisory meetings are on deck as well, each involving much-debated clinical trial results.
Here are five decisions to watch in the third quarter:
Sage and Biogen’s zuranolone for depression
Though they vary, estimates show depression has become more prevalent.
A study published in the American Journal of Preventive Medicine last year found that, in 2020, nearly one in 10 people in the U.S. experienced depression. That same year, around 21 million adults and 4.1 million adolescents aged 12 to 17 had at least one episode of major depressive disorder, which is one of the most common mental disorders, according to the National Institutes of Health.
While treatments are available — in particular, so-called SSRI drugs like Prozac, Lexapro and Zoloft — they don’t work for everyone. For years, patients and doctors have sought additional, effective options from pharmaceutical companies.
Sage Therapeutics hopes one of its drugs, called zuranolone, can be one. The Cambridge, Massachusetts-based biotechnology company and its development partner Biogen late last year asked the FDA to approve zuranolone as a treatment for both major depressive disorder and postpartum depression, and expect a decision from the agency by August 5.
So far, zuranolone has delivered mixed results in clinical testing. The drug appears to act faster than other depression therapies, but its effects are relatively small and wane rather quickly. And while patients who took it didn’t show signs of withdrawal or suicidal ideation — main concerns with other antidepressants — they did experience side effects like drowsiness, dizziness, headache and sedation.
Nevertheless, analysts expect zuranolone to secure FDA approval and become a lucrative product for Sage and Biogen. The team at RBC Capital Markets, for instance, forecasts $2.5 billion in peak annual sales of the drug, based in part on recent feedback from doctors and patients. — Jacob Bell
Eisai and Biogen’s Leqembi for Alzheimer’s
The FDA is weighing whether to upgrade the conditional OK it gave to a closely watched Alzheimer’s medicine earlier this year into a full approval.
If it does, the number of Alzheimer’s patients able to access the medicine, which is sold under the brand name Leqembi, should grow significantly. So, too, should sales, representing what Wall Street sees as a multibillion-dollar opportunity for Leqembi’s developers, Eisai and Biogen.
Analysts believe there’s a high likelihood the FDA grants an expanded approval. The main trial backing Eisai and Biogen’s application found patients on Leqembi declined 27% slower than those on placebo over an 18-month period. And though drug-treated patients had higher rates of a key safety concern known as “ARIA,” some experts have argued these side effects tend to resolve on their own or are generally treatable.
The trial data were enough to convince a committee which advises the FDA on brain medicines that Leqembi indeed benefits patients. The committee unanimously voted in favor of the drug during a recent meeting, further improving its chances at full approval. While the FDA isn’t required to follow the recommendations of its advisers, it typically does. — Jacob Bell
Sanofi and AstraZeneca’s nirsevimab for RSV
After decades of stop-and-start research, the first two vaccines for respiratory syncytial virus won FDA approval this year. GSK was the first to gain clearance, with Pfizer following closely behind with its own candidate. Both companies’ shots were approved to prevent RSV infections in adults 60 years and older, although Pfizer is also exploring vaccination for pregnant women.
While RSV is a common infection that typically causes flu-like symptoms, older adults and infants can be especially vulnerable. Tens of thousands of people in both groups are hospitalized each year in the U.S., and thousands die, according to the Centers for Disease Control and Prevention.
AstraZeneca and Sanofi aim to provide an alternative to vaccination with a protective therapy, a monoclonal antibody called nirsevimab, that’s designed to prevent lower respiratory tract disease in infants.
Data from the companies showed nirsevimab was 83% effective in preventing hospitalization when given to infants under one year of age. Testing also compared the drug to another antibody treatment for RSV, sold as Synagis, which is limited to use in high-risk infants and requires monthly injections.
Nirsevimab was generally safe, with fever and rash the most common adverse events reported in testing.
In June, a panel of FDA advisers backed nirsevimab, voting unanimously to recommend its use in infants. The panel also voted 19-2 in favor of using the drug in children up to two years old who remain vulnerable during their second RSV season.
The drug has been approved in Europe since November under the brand name Beyfortus. In the U.S., an FDA decision is expected in September, but it’s not clear whether that will be in time for the drug to be made available ahead of the fall RSV season.
Analysts predict strong sales for the drug, with Jefferies analyst Michael Yee, estimating it could eventually earn $3 billion in peak annual sales. — Delilah Alvarado
Iveric’s Zimura for geographic atrophy
In February, the FDA made Syfovre, from Apellis Pharmaceuticals, the first marketed medicine for a common type of vision loss known as geographic atrophy. A second could follow this quarter if the regulator clears Zimura, a medicine developed by Iveric Bio.
The treatments work similarly, blocking activation of a part of the immune system in such a way to slow the disease’s progression. While both companies can point to positive biological effects, the benefit of treatment on visual sharpness hasn’t yet been proven. The drugs also come with some safety risks that may grow with time.
Still, they’re viewed as potential blockbuster medicines, an outlook that is buoyed by Syfovre’s fast start on the market. Larger drugmakers have shown interest, too: Astellas Pharma paid $5.9 billion to acquire Iveric in May, and Apellis was reportedly courted by potential suitors, too.
Astellas is leaning on Zimura to build an eye drug business and help soften the blow when its top cancer drug, Xtandi, loses patent protection in 2027.
But much could depend on Zimura’s labeling. Syfovre is injected into the eye once every 25 to 60 days, while Zimura has been tested as a monthly injection for the first year and every other month afterwards. Apellis’ studies also included a broader range of patients, which, some analysts have suggested, could give its drug an advantage commercially.
The FDA is expected to make a decision by Aug. 19. — Ben Fidler
Alnylam’s Onpattro for ATTR cardiomyopathy
The 2018 approval of Onpattro was a milestone, giving its maker, Alnylam Pharmaceuticals, its first marketed product after two decades of research and ushering in the first drug using a gene-silencing technique called RNA interference.
Yet an upcoming FDA meeting on Onpattro’s next potential use, for the genetic heart condition transthyretin amyloidosis cardiomyopathy, could be just as important to the biotech company’s future.
Onpattro is already approved for a rarer form of the disease that affects the nerves. Alnylam still isn’t consistently profitable, though, and a clearance in cardiomyopathy could change that. The heart form of the disease is far more common, and the only available treatment option, Pfizer’s Vyndamax, generated more than $2.4 billion in sales in 2022.
Alnylam is trying to improve on Vyndamax, first with Onpattro and eventually a more convenient version of the drug that’s in a Phase 3 trial. But while clinical testing showed patients treated with Onpattro performed better on a walking test associated with heart health, Wall Street analysts questioned how meaningful those results were.
Onpattro also hasn’t yet been proven to extend lives or prevent hospital stays, as Vyndamax has.
Alnylam has said the FDA will hold an advisory committee meeting to discuss the application, a move the regulator makes when it wants input from outside experts. A date hasn't been set, but multiple analysts expect the panel to take place this summer, weeks ahead of an Oct. 8 decision deadline.
The outcome will affect not just Alnylam but others, like BridgeBio Pharma, Intellia Therapeutics and Ionis Pharmaceuticals, with rival medicines in clinical testing. — Ben Fidler
Bonus: Brainstorm’s NurOwn for ALS
Within the last year, the FDA has approved two new medicines for ALS, the nerve-destroying disease thrust into the spotlight through the viral Ice Bucket Challenge. A New-York based biotech hopes to add a third to that list.
The medicine, called NurOwn, is derived from stem cells and meant to prompt the production of molecules that help nerve cells grow and survive. In 2020, NurOwn failed a key clinical trial that its developer, Brainstorm Cell Therapeutics, had anticipated would support an approval. Despite that setback, Brainstorm has argued its treatment “represents a significant contribution to ALS therapy.”
But regulators haven’t been so convinced. The FDA initially declined to review Brainstorm’s application, and is only evaluating it now because the company filed paperwork “over protest” — an unusual regulatory move to force the agency’s hand.
Ahead of a decision deadline of Dec. 8, the FDA plans to convene a group of experts who advise the agency on cell and gene therapies to give input on NurOwn. That meeting is scheduled for Sept. 27.
“We remain confident in NurOwn and believe our data support regulatory approval,” Stacy Lindborg, BrainStorm’s co-CEO, said in a statement earlier this month. “As is the case with most ALS research, our clinical program generated complex results, which deserve a thoughtful and holistic review by scientists, ALS experts, FDA reviewers, advocates, and patients.” — Jacob Bell