5 FDA decisions to watch in the third quarter
6 min read
Two of last year’s largest biotechnology company acquisitions centered on a new type of treatment for schizophrenia. By the end of September, the first of those therapies could win Food and Drug Administration approval, a decision that would highlight the new attention being paid to psychiatric drugs.
Other novel psychiatric treatments are working their way through testing, too, including psychedelics like MDMA and psilocybin. The FDA has a tough decision to make on that front, as a panel of its advisers recently panned the use of MDMA-assisted psychotherapy for post-traumatic stress disorder.
Elsewhere, Gilead Sciences might get an OK for a drug it recently acquired via its deal for CymaBay Therapeutics and a new kind of cell therapy could reach market. Here are five FDA decisions to watch in the third quarter:
Bristol Myers’ Kar-XT for schizophrenia
For the first time in decades, a truly new form of antipsychotic could be coming to market.
The drug, known as KarXT and developed by Karuna Therapeutics, already has multiple wins under its belt. Two large, placebo-controlled trials found schizophrenia patients given it had significantly greater reductions on a scoring system that measures the severity of their symptoms. The drug also seems to work fast, with the main treatment period of both studies lasting five weeks.
While KarXT does have side effects, it doesn’t appear to cause the excessive weight gain, restlessness or movement issues that older antipsychotics often elicit. Unlike those medications, KarXT and a rival medicine from Cerevel Therapeutics work by stimulating a kind of protein that controls the release of acetylcholine, a chemical important to brain function.
Doctors foresee KarXT being an attractive option for schizophrenia patients, who often switch medications because of side effects or because the drugs aren’t controlling their disease well enough. Still, there are concerns that insurance providers will resist covering a drug like KarXT, since many generic and inexpensive antipsychotics are already available.
On Wall Street, analysts expect KarXT will secure approval by the FDA’s Sept. 26 decision deadline. Some even believe the drug will generate more than $10 billion in yearly sales at its peak. Whether that comes to fruition is in the hands of Bristol Myers Squibb, which recently bought Karuna for $14 billion.
“I think you’re gonna get a massive bolus of early adopters,” said Paul Matteis, an analyst at the investment firm Stifel, in an interview late last year. “And I think Bristol [Myers] just has to not mess it up.” — Jacob Bell
Lykos’ MDMA-based therapy for PTSD
Lykos Therapeutics believes it can build a business around MDMA — also known as the party drug ecstasy. To do that, the company, formerly named MAPS Public Benefit Corp., identified a “novel” version of the drug and set up a series of patents to protect it.
But Lykos needed supportive data as well. So far, it has run two late-stage studies evaluating MDMA as an aid to talk therapy for people with moderate-to-severe post-traumatic stress disorder. Results showed that, over the course of 18 weeks and three treatment sessions, patients who received MDMA had a significantly greater reduction on a scale measuring the severity of PTSD symptoms, compared to those who just got talk therapy.
The company thought the trials provided enough evidence to make MDMA the first psychedelic-assisted therapy approved by the FDA. Those hopes appear slimmer, however, following a recent meeting of agency advisers.
The panel of advisers voted almost unanimously against the drug, citing concerns about its safety and the ways Lykos conducted the trials. Allegations of ethics violations, including sexual misconduct and data suppression, also weighed on Lykos’ application.
The FDA isn’t required to follow the recommendations of its advisers. But it typically does, meaning the odds of approval are likely lower following the meeting. The agency is expected to make a decision by Aug. 11. — Jacob Bell
Gilead’s seladelpar for primary biliary cholangitis
After spending more than $20 billion on cancer drug deals, Gilead got back to its liver disease roots with its February acquisition of CymaBay. The $4.3 billion buyout gave Gilead an experimental treatment for primary biliary cholangitis, a chronic condition caused by the toxic build-up of bile acid in the liver.
Called seladelpar, the drug would expand Gilead’s liver disease portfolio beyond hepatitis if approved by the FDA’s target decision date of Aug. 14. The company estimates about 130,000 people in the U.S. have primary biliary cholangitis, or PBC, and expects that its salesforce would cover about 80% of the prescribers who treat the condition.
Two other drugs are approved in the U.S. for PBC: Intercept Pharmaceuticals’ Ocaliva and Ipsen’s more recently cleared Iqirvo. Both carry notable safety warnings, meaning that the labeling of seladelpar, if OK’d by the FDA, could play an important role in how well it’s adopted. Testing of seladelpar in another liver condition called MASH was previously halted on safety worries that later proved unfounded.
Gilead has highlighted seladelpar’s effectiveness in curbing the itching associated with PBC and expects the drug, if approved, to contribute “modestly” to sales this year. — Ned Pagliarulo
Ascendis’ TransCon PTH for hypoparathyroidism
By the end of the year, Takeda will stop making the only prescription medication available in the U.S. for a rare endocrine condition called hypoparathyroidism, ending a drug launch marred by slow sales and production issues. But a new option could emerge this quarter if the FDA approves TransCon PTH, a therapy developed by Danish biotech Ascendis Pharma.
Ascendis’ drug provides a replacement form of parathyroid hormone, which is lacking in the estimated 77,000 people in the U.S. with hypoparathyroidism, causing low calcium levels and other health problems. It’s based on a technology, TransCon, that Ascendis uses to fine-tune the properties of a medicine for delivery.
Phase 3 study results in 2022 showed about 79% of trial participants treated with TransCon PTH had normal calcium levels. Most didn’t need vitamin supplements afterwards. Ascendis has since won approvals in Europe and the U.K. But the company has faced a tougher road in the U.S. The FDA rejected TransCon PTH in 2023 due to manufacturing concerns and, in May, delayed its verdict by three months as the responses Ascendis provided constituted a “major amendment” to its application.
A decision could finally come by Aug. 14 and, if positive, unlock what some analysts forecast as a multibillion-dollar revenue opportunity. An approval would also keep Ascendis ahead of several would-be competitors, among them AstraZeneca, which recently acquired a startup with a drug in late-stage testing. — Ben Fidler
Adaptimmune’s afami-cel for synovial sarcoma
Since 2017, the FDA has approved six CAR-T cell therapies and, earlier this year, cleared for the first time a different kind of immune cell treatment. Another type of cellular medicine could reach the market this quarter if the agency OKs an experimental drug from biotech Adaptimmune.
Formed in 2008, Adaptimmune is focused on TCR cell therapies, which are similar to CAR-T treatments but rely on protein receptors that can recognize intracellular targets. That capability could make TCR cell therapies better able to attack the solid tumors CAR-T struggle to treat.
But Adaptimmune has had difficulty proving their worth. In recent years, the company lost both GSK and Roche as partners, laid off staff and restructured its pipeline. At about $1 apiece, shares are worth a fraction of their initial public offering price in 2015.
The company’s fortunes could shift if the FDA approves afami-cel, a TCR therapy for a rare soft tissue cancer called synovial sarcoma. Wall Street analysts are optimistic the FDA will clear afami-cel by an Aug. 4 deadline, as the agency hasn’t called on outside advisors to scrutinize the data or, executives have said, communicated issues with Adaptimune’s study results. The company has financial room to work with, too, having cut deals with Galapagos and Hercules Capital in May.
Still, Adaptimmune faces questions on afami-cel’s market potential. Analysts at Mizuho Securities have lowered peak annual sales projections to $174 million amid expectations of “more conservative uptake” than they previously thought. While an approval “may bring validation” to Adaptimmune, “strong commercial performance … will be important to support a positive view” of the company’s prospects, wrote Leerink Partners’ Thomas Chang in a recent client note. — Ben Fidler
