Bristol Myers Squibb's Deucravacitinib Fails Mid-Phase IBD Trial Despite Strong Commercial Outlook

Compiled by | Fan Dongdong

Recently, Bristol-Myers Squibb’s (BMS) potential blockbuster deucravacitinib encountered its first setback, as the drug’s mid-stage trial for ulcerative colitis (IBD) failed to meet primary or secondary endpoints.

This clinical trial randomized 131 patients with moderate-to-severe ulcerative colitis to receive either the oral TYK2 inhibitor deucravacitinib or a placebo for 12 weeks. Unfortunately, the trial results indicated a complete failure of deucravacitinib, which missed both the primary clinical remission endpoint and the secondary efficacy endpoints. The secondary endpoints in this study focused on clinical and endoscopic response, as well as histologic improvement.

Media reports indicate that Bristol-Myers Squibb has downplayed the significant setback in this deucravacitinib trial, reiterating its forecast that sales of the drug will exceed $4 billion by 2029. The company noted that considerable market opportunities remain, with some reports suggesting that the drug may still achieve a turnaround with positive outcomes in ulcerative colitis, as data from a second, higher-dose study of deucravacitinib has yet to be released.

Even so, the failure of the first mid-stage ulcerative colitis trial for deucravacitinib undoubtedly represents a setback to Bristol-Myers Squibb’s initial decision to divest Otezla. During Bristol-Myers Squibb's evaluation of the Celgene acquisition, the Federal Trade Commission mandated the sale of Otezla as a condition for closing the transaction, a move intended to ensure that Bristol-Myers Squibb would retain sufficient incentive to develop its proprietary oral psoriasis drug, deucravacitinib.

Bristol-Myers Squibb's confidence in deucravacitinib was previously vindicated when the drug outperformed Otezla in a Phase III psoriasis trial. However, deucravacitinib recently suffered a setback following a failed trial in ulcerative colitis. As the drug's future indications expand beyond psoriasis, it remains to be determined whether this failure in the ulcerative colitis trial is merely an isolated incident or a harbinger of broader efficacy limitations inherent to deucravacitinib itself.

This drug is a next-generation small-molecule TYK2 inhibitor developed by Bristol-Myers Squibb. Unlike known JAK inhibitors, deucravacitinib selectively binds to the pseudokinase domain (JH2) of TYK2, inhibiting TYK2 kinase activity through an allosteric mechanism. It exhibits weak inhibitory activity against JAK1-3, thereby effectively reducing adverse effects associated with JAK1-3 inhibition.

Currently, researchers are enrolling patients with conditions such as Crohn's disease, psoriatic arthritis, and lupus in Phase 2 and Phase 3 clinical trials for this therapy. Over the coming years, these clinical trials will generate a series of data that will define the development prospects for deucravacitinib in indications beyond psoriasis.

Reference:

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

https://www.fiercebiotech.com/biotech/bristol-myers-deucravacitinib-flunks-midphase-ibd-trial-raising-questions-about-potential