5 FDA decisions to watch in the second quarter – BioPharma Dive

The first quarter of 2022 was one to forget for the biotech industry.

A public market downturn that began last year accelerated, sending the stock values of many biotech companies spiraling lower. The pace of drugmaker initial public offerings, which set a record in 2021, slowed to a trickle, making the path to Wall Street harder for emerging startups. Biotechs tightened their purse strings, leading to a string of restructurings.

Still, there were a few bright spots.The Food and Drug Administration approved a first-of-its-kind cancer immunotherapy, while a pioneering gene editing treatment continued to show promise and a major acquisition closed, calming concerns of greater regulatory scrutiny on buyout deals.

Several key FDA decisions lie ahead in the second quarter and each, if positive, may help the sector regain its momentum. Here are five to watch:

FDA advisory committee meetings are important moments for drugmakers as their outcomes can have a significant impact on a prospective medicine's approval chances. A two-day gathering in June is even more important for Bluebird, which could run out of money if the FDA doesn't approve two gene therapies a group of experts are set to review.

The gene therapies, known as beti-cel and eli-cel, would be just the third and fourth gene therapies for inherited diseases to reach market in the U.S. They would represent significant medical advances for patients with the blood disease beta thalassemia and the childhood brain disorder cerebral adrenoleukodystrophy.

Approvals also would lead the FDA to award the company with two priority review vouchers that can speed up drug reviews and be sold to other companies.

Bluebird has said those vouchers are critical to its financial future. In March, the company's top financial executive resigned amid a cash crunch that could leave the company insolvent within a year. Selling the vouchers could extend its runway and give Bluebird the chance to rebound.

However, Bluebird needs the blessing of the FDA and its advisers first, neither of which are a given. Both programs have been slowed in the past due to safety concernsand testing of eli-cel is on hold after a clinical trial participant developed a type of bone marrow cancer. The FDA extended its review of both drugs earlier this year.

The two-day advisory panel will take place on June 9 and June 10. The FDA will decide whether to approve beti-cel by Aug. 19 and eli-cel by Sept. 16.

Bristol Myers Squibb has been largely absent from major dealmaking since absorbing Celgene in a merger three years ago. However,the one time the pharma company did spring for a deal was in October 2020, when it paid $13 billion to buy MyoKardia and a heart drug known as mavacamten.

Bristol Myers was willing to pay that high price on optimism that mavacamten could become a top seller. On a conference call in February, CEO Giovanni Caforio pointed to the drug, which treats a typically inherited heart condition known as hypertrophic cardiomyopathy, as one of three emerging treatments in its pipeline with "at least $4 billion in revenue potential." Hitting those numbers will be key for Bristol Myers, as some of its most lucrative products will lose patent protection later this decade.

Still, commercial success is no guarantee. Many patients with hypertrophic cardiomyopathy don't have symptoms, and other medications and surgical options are available. Competition could be looming in the form of a similar drug from Cytokinetics that's in late-stage testing. On the February call, some analysts also questioned Bristol Myers' projections, which rely heavily on a sharp increase in diagnosis rates.

The FDA in November extended its review of mavacamten to evaluate a proposed post-approval patient monitoring plan, the details of which Bristol Myers hasn't shared. Its decision deadline is April 28.

The FDA is set to issue a verdict by June 29 on what could become the first new ALS drug to reach the U.S. market in five years.

ALS, better known to some as amyotrophic lateral sclerosis or Lou Gehrig's disease, is a progressive and fatal disorder hallmarked by the breakdown of nerve cells and the deterioration of essential functions like walking, eating and breathing. Patients with the disease typically live just two to five years after being diagnosed.To date, the FDA has cleared only two treatments specifically for ALS, each with limited effects on function and survival.

Amylyx Pharmaceuticals, a small drug company based in Cambridge, Massachusetts, believes it has another option in a pairing of chemicals named AMX0035. In a study of about 140 patients, Amylyx said those who received its medicine declined significantly slower compared to those on a placebo, as measured by a rating scale used to evaluate day-to-day functions in ALS patients. Amylyx also said that further analyses from an extension phase of the study found a benefit on survival.

The company, patient advocates and some doctors believe these outcomes offer enough evidence to approve AMX0035. The FDA has shown interest in the drug as well, allowing Amylyx to submit it while running another, larger study to confirm the results seen so far. However, the agency also has reservations about the way Amylyx designed its key study and the ways in which data were analyzed. Such concerns were on display during a meeting this week, in which neuroscience and drug development experts advised the FDA against approving AMX0035 in a narrow vote.

That vote puts the agency in a difficult position. ALS patients and advocacy groups have campaigned for the approval of more treatments, including Amylyx's, noting the limited options currently available as well as the devastating and fatal nature of their disease. The FDA has met with advocates and said it's listening to them, but with the crux of Amylyx's approval application in doubt, regulators could hold off green-lighting the company's drug until that larger study produces full results in 2024.

By late June, the FDA will decide whether to approve Bristol Myers' CAR-T cell therapy Breyanzi for earlier treatment of a common form of lymphoma.

To date, the complex cancer treatments have only been cleared for use after patients have run out of other options, limiting their reach and commercial potential. However, last year Bristol Myers and Gilead presented clinical trial data showing their respective CAR-T therapies Breyanzi and Yescarta outperformed standard "second-line" treatment, a combination of chemotherapy and stem cell transplant.

The results were a major proof point for CAR-T, which had reached market in the U.S. based on smaller studies without control arms. They were also validation for Bristol Myers and Gilead, both of which spent billions of dollars to acquire the products.

Gilead is likely to beat Bristol Myers to an approval, with an FDA decision expected imminently for Yescarta in second-line treatment. Yescarta has also been approved for longer, with an additional clearance for another lymphoma type.

However, approvals in second-line lymphoma could also draw renewed attention to the cost and manufacturing issues of CAR-T treatment. Bristol Myers priced Breyanzi at $410,000, while Yescarta has a list price of $373,000. Both companies require several weeks to produce the personalized treatments, a challenge that may grow more difficult if a broader group of patients are eligible.

Over the past year, the FDA office in charge of reviewing new cancer medicines has revisited its approach to accelerated approvals, most notably convening a meeting of outside experts last spring to review six previously granted OKs.

Agency officials have penned opinion pieces signaling tougher standards. FDA pressure has also led a number of companies to withdraw accelerated approval applications. Some companies have even pulled previously cleared drug indications after they were unable to confirm benefits observed in earlier testing.

The FDA's scrutiny appears to be turning next to a class of cancer medicines known as PI3K inhibitors, several of which are already on the market. In late April, the agency will again gather its panel of advisers to review whether randomized trial data is needed to appropriately support their use.

The group will also discuss an application by TG Therapeutics for accelerated approval of a combination drug regimen containing its marketed PI3K blocker Ukoniq. Previously, the FDA had announced an investigation into a possible increased risk of death with the medicine.

The agency has set a target decision date of June 25 for TG's treatment combination.

Already, the FDA's focus on PI3K inhibitors appears to have had an effect. In January, Gilead said it would withdraw two indications for its drug Zydelig after having difficulty enrolling patients in confirmatory studies. In addition,the agency told MEI Pharma and partner Kyowa Kirin this month that they would need to gather more data for their experimental PI3K inhibitor before seeking approval.

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5 FDA decisions to watch in the second quarter - BioPharma Dive