Bristol Myers Squibb's next-gen autoimmune med starts high-stakes FDA review amid classwide JAK scrutiny

After the FDA slapped an updated safety warning on marketed oral JAK inhibitors for inflammatory diseases, market watchers have started worrying about other candidates in the pipeline. Bristol Myers Squibb now has a date to learn how the agency views its novel medicine deucravacitinib, with blockbuster sales at stake.

The FDA has accepted Bristol Myers’ application for deucravacitinib to treat moderate to severe plaque psoriasis, with a decision targeted for Sept. 10, 2022, the company said Monday. The European Medicines Agency has also started reviewing a similar submission.

BMS has big expectations for the potentially first-in-class TYK2 inhibitor. The New York pharma has said deucravacitinib could reach $4 billion sales at peak with possible indications in a variety of inflammatory diseases.

Problem is, TYK2, also colloquially known as JAK4, is part of the JAK family. Amid the FDA’s classwide safety scrutiny on oral JAK inhibitors’ heart risks, some industry watchers have raised concerns that the agency might treat TYK2 drugs with the same brush.

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Deucravacitinib has a differentiated safety profile that has shown it doesn’t have the downstream effects of JAK1/2/3, which are targeted by existing JAK inhibitors, Samit Hirawat, BMS’ chief medical officer, said in a recent interview. In testing, the drug didn’t demonstrate any JAK-like acute effects on liver dysfunction, anemia, abnormal blood platelet count or cholesterol level, he pointed out. Rupert Vessey, BMS’ president of research and early development, attributed deucravacinib’s unique safety profile to a target binding property that’s different from existing JAK inhibitors.

To win U.S antitrust clearance for the gigantic Celgene merger in 2019, BMS decided to sell Celgene’s fast-growing blockbuster oral psoriasis med Otezla to Amgen in favor of the then-phase 3 deucravacitinib.

Two sets of phase 3 plaque psoriasis data unveiled earlier this year suggested BMS made the right choice. In the POETYK PSO-1 and POETYK PSO-2 studies, deucravacitinib beat Otezla by helping more patients achieve 75% skin clearance.

Otezla sales in the third quarter grew 13% in the third quarter to $609 million. The PDE4 inhibitor is on track to gain an FDA label expansion in December to reach mild-to-moderate psoriasis.

RELATED: Bristol Myers Squibb's deucravacitinib flunks midphase IBD trial, raising questions about potential blockbuster

But after the merger, the BMS drug candidate took a hit in October when it failed a phase 2 trial in ulcerative colitis. BMS has a second phase 2 UC trial to examine deucravacitinib at a higher dose, Hirawat noted. Inflammatory bowel disease typically requires a dose two- to three-times higher than would be used to treat other inflammatory diseases of the skin, he added.

Besides UC, the company has another phase 2 for the TYK2 drug in Crohn’s disease. Outside of IBD, a phase 3 study is evaluating deucravacitinib in psoriatic arthritis.

All those indications are building blocks to deucravacitinib’s $4 billion peak potential by 2029 by BMS’ estimate. BMS is counting on several new drugs, including deucravacitinib, for growth in the latter half of the decade, when three of its top-selling drugs—Revlimid, Opdivo and Pfizer-partnered Eliquis—are expected to face generic competition.

Another $4 billion-plus opportunity in BMS’ calculation, targeted heart drug mavacamten, recently hit a regulatory setback as the FDA has delayed a decision date by three months to April 28, 2022.