A drug that Bristol Myers Squibb is developing for use across a wide range of autoimmune diseases has failed a mid-stage clinical trial in ulcerative colitis, dimming its prospects in that indication. But another study of the drug, deucravacitinib, is continuing at a higher dose in ulcerative colitis patients, and the company is also evaluating the compound in other conditions.
According to preliminary results announced Thursday, the BMS drug did not beat a placebo measured against the study’s main goal of showing clinical remission in ulcerative colitis, an inflammatory bowel disease. BMS provided no specific details about those results, but the company did say the drug’s safety was consistent with earlier studies.
Deucravacitinib is a small molecule designed to block tyrosine kinase 2 (TYK2), an enzyme that mediates immune and inflammatory signaling pathways. While TYK2 is a key part of normal immune responses, it also drives pathways associated with several autoimmune diseases. The drug selectively blocks TYK2 but not other enzymes, a feature that distinguishes it from Janus kinase (JAK) inhibitors, a class of drugs that is used to treat autoimmune conditions. The entire JAK inhibitor class has come under FDA scrutiny due to a higher risks of cardiovascular events and cancer, according to results of post-marketing research.
The ulcerative colitis Phase 2 study enrolled 131 patients whose disease was classified as moderate to severe. Those patients were randomly assigned to receive the experimental drug or a placebo for 12 weeks. In addition to missing the main goal, the drug also failed to achieve any of the secondary goals that would indicate response or improvement. Deucravacitinib’s prospects in ulcerative colitis treatment now ride on a separate Phase 2 study that is testing a higher dose.
The clinical trial failure in ulcerative colitis comes eight months after BMS reported positive Phase 3 results for deucravacitinib in plaque psoriasis. That study compared the drug against a placebo as well as Otezla, a blockbuster autoimmune disease drug that BMS sold to Amgen in 2019. Otezla was part of Celgene, which BMS acquired two years ago for $74 billion. Though Otzela works in a different way than deucravacitinib, federal antitrust regulators feared that BMS’s ownership of both drugs would be anticompetitive. To allay those concerns, BMS agreed to sell the Celgene asset to Amgen for $13.4 billion. Under Amgen, Otzela accounted for nearly $2.2 billion in global sales in 2020, according to the company’s annual report.
In a prepared statement, Chief Medical Officer Samit Hirawat said BMS is committed to deucravacitinib. In addition to inflammatory bowel disorders, BMS has clinical studies underway in psoriatic arthritis and lupus, among other autoimmune conditions. BMS still projects deucravacitinib will become a blockbuster, reaching an estimated $4 billion in revenue in 2029.
Photo by Flickr user Ed Uthman via a Creative Commons license
