5 FDA decisions to watch in the third quarter

So far in 2022, the Food and Drug Administration’s main review office has approved 16 new medicines. The agency has recently cleared between 45 to 50 treatments each year, so the second half of the year could be busy if historical trends hold. 

Three of the most important approval decisions the FDA will make are for drugs it’s been vetting for many months, having delayed previously scheduled deadlines. The next quarter will finally bring a verdict on two gene therapies and a closely watched ALS medicine. 

The regulator also faces an enormously consequential decision on COVID-19 vaccines, and could make approval choices that have ripple effects for other companies in the industry. 

Here are five FDA decisions to watch:

The next COVID-19 vaccine boosters 

The coronavirus pandemic is in a different phase than it was 18 months ago, when COVID-19 vaccines from Pfizer and Moderna were first authorized. The majority of the U.S. population is vaccinated with at least two shots and isn’t as susceptible to COVID-19’s most severe outcomes as before. Mask mandates and travel restrictions have been relaxed. 

But COVID-19 remains a threat. Protection from the disease appears to wane within months of either infection or vaccination. The virus continues to mutate, driving new surges as well as upping the urgency to update the composition of available vaccines. This quarter, public health officials will likely decide how they plan to adjust.  

Their decision won’t be easy. Pfizer and Moderna have prepared updated shots, but they target older strains of the virus, not the omicron subvariants currently spreading. A one-strain shot Pfizer developed spurred more virus-fighting antibodies against omicron than its two-pronged version, complicating the questions facing drug regulators. There may be a new viral threat by the time the next boosters are authorized, too.  

At an advisory meeting on Tuesday, independent experts agreed the next boosters should contain a two-pronged attack with some type of omicron-fighting component. But it’s still unclear what those shots should look like, or when they might be available. The U.S. government aims to start a booster campaign in October. 

Amylyx Pharmaceuticals’ AMX0035 for amyotrophic lateral sclerosis

By the end of September, the FDA may, for the first time in more than five years, approve a new medicine for amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig’s disease.

Developed by the Massachusetts-based company Amylyx Pharmaceuticals, the medicine showed positive effects on function and survival in a placebo-controlled study of about 140 participants. Amylyx is currently running another clinical trial to affirm the benefits of its drug, with a target enrollment of approximately 600 volunteers. Data are expected in late 2023.

Initially, the FDA wanted to see results from this larger trial before accepting an approval application. But, following pushback from patient advocacy groups, the agency decided to review Amylyx’s drug while the company ran its confirmatory study.

Despite that reversal, analysts remain uncertain about the drug’s approval odds. In March, the FDA convened a committee of experts to weigh whether it should be cleared for market. The committee voted no by a narrow margin. Although the agency isn’t required to follow such recommendations, it typically does.

Additionally, FDA staff voiced concerns at the March meeting about the way Amylyx designed that smaller study and analyzed its data.

Amylyx may still come out with a victory, though. The FDA just this month released a five-year action plan meant to “aggressively” address the challenges drugmakers face developing new treatments for rare neurodegenerative diseases, with ALS research being a top area of interest.

The agency also recently extended its deadline for reviewing Amylyx’s application, which some analysts believe bodes well for approval. The team at Evercore ISI, for example, recently examined more than 150 cases where the FDA held an advisory committee meeting for a drug. Of the 23 cases in which it also took extra time to evaluate applications, 18 resulted in the drug being cleared for market.

Some doctors, and even Amylyx’s co-founders, have noted the drug is far from a cure. Patients who took it in the smaller trial still declined, and the chances of them living up to two years post-enrollment were about 50%.

Even so, patient advocates have called for approval of the drug as there are only two other therapeutic options. Each has limited effects on either function or survival. 

Amylyx’s drug, known as AMX0035, is already approved in Canada under the brand name Albrioza.

Bluebird bio’s beti-cel for beta thalassemia and eli-cel for CALD

Bluebird’s future looks to be on firmer ground after a panel of FDA advisers in June voted unanimously in favor of both gene therapies the drugmaker has in front of the agency. 

FDA staff had laid out a number of concerns with the treatments, which are for a rare blood condition and an inherited brain disease. But in each case the group of independent experts agreed the benefits of Bluebird’s drugs outweigh the safety risks, including the potential that they may cause cancer. 

Approvals, should they come by the FDA’s decision dates of Aug. 19 and Sept. 16, would be milestones for gene therapy and potentially financial salvation for Bluebird. The biotech, long a richly valued leader in the field, is quickly running out of cash and has warned it may not stay solvent through early next year. Regulatory clearances could give Bluebird a chance to sell its products and, more immediately, special regulatory vouchers it would receive. 

For beta thalassemia and CALD patients, approvals would make available much-needed treatment options that may provide long-lasting benefits. 

And for gene therapy more broadly, approvals could help lift a sector that’s dealt with more setbacks than successes over the past 18 months. 

Bristol Myers Squibb’s deucravacitinib for plaque psoriasis 

Approval of deucravacitinib by the FDA’s deadline of Sept. 10 would keep Bristol Myers on track to replace some of the revenue it’s expected to lose following patent expirations later this decade. The psoriasis treatment is the last of three Bristol Myers drugs, each of which it forecasts will hit $4 billion in peak annual sales, due an approval decision in 2022.

The first two — the cancer immunotherapy Opdualag and the heart drug Camzyos — made it across regulators’ desks without a hitch. Deucravacitinib, by comparison, could cause more concerns. It could be the first approved drug to turn down the autoimmune reactions that cause psoriasis by blocking a protein called TYK2, which is part of a family known as Janus kinases, or JAKs. 

Other autoimmune drugs blocking JAKs have come under FDA scrutiny because they are associated with heart complications, cancer and serious infections. The drugs’ labels include a prominent warning of these risks.

Bristol Myers claims deucravacitinib’s precise targeting of TYK2 could help it avoid a similar warning. A clean label could help it become a first-choice drug for psoriasis, according to analysts from Bernstein.

About 80% of Bristol Myers’ revenue is from drugs due to lose market exclusivity by the end of the decade, the Bernstein analysts write. Combined, the cancer drugs Revlimid and Opdivo and the blood thinner Eliquis accounted for $31 billion of the $46 billion in total company sales last year. 

Novartis and Beigene’s tislelizumab in esophageal squamous cell carcinoma

Novartis has watched its pharmaceutical peers capitalize on cancer immunotherapies known as checkpoint inhibitors, which have become standard treatments for dozens of tumor types as well as some of industry’s most lucrative drugs. The Swiss company could finally enter the market if the FDA approves tislelizumab for a form of throat cancer by its July 12 deadline. 

Novartis has bet heavily on tislelizumab, paying its maker, China-based biotech Beigene, $650 million upfront for partial rights in 2021. The drug is already approved in China for a form of lymphoma as well as bladder cancer, and currently is in testing for multiple other tumor types. It’s under review in Europe as well. 

Yet U.S. approval isn’t a given. Though the FDA has approved more than half a dozen drugs that work like tislelizumab, the regulator has recently raised the bar for immunotherapies, particularly for indications like esophageal squamous cell carcinoma in which some are already available. The FDA earlier this year rejected two checkpoint inhibitors from Eli Lilly and Coherus BioSciences, while it has pressured companies to withdraw indications unsupported by strong evidence of clinical benefit. 

Novartis may have a better case, though. The trial supporting its application in throat cancer is based on the kind of global trial the regulator prefers. Lilly’s filing was sent back because the regulator didn’t find its data generalizable to the U.S. population.

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