A phase 2 trial of Merck & Co.’s anti-TL1A monoclonal antibody has missed its primary endpoint, closing off one avenue for expansion of an asset acquired in a $10.8 billion takeover. The setback was offset by a midphase win in another indication.
Merck acquired the antibody, tulisokibart, when it bought Prometheus Biosciences in 2023. Racing Roche’s afimkibart and Sanofi and Teva’s duvakitug, Merck expanded on Prometheus’ work by launching a broad R&D program. The U.S. Big Pharma inherited a phase 2 study in systemic sclerosis associated with interstitial lung disease (SSc-ILD) and started trials in indications including hidradenitis suppurativa (HS).
In its second-quarter earnings update, the drug developer revealed that the SSc-ILD study missed its primary endpoint. As a result, Merck is ending the SSc-ILD program, although the company pointed out that no new safety concerns were seen in the failed study.
In an earnings call Tuesday, Dean Li, M.D., Ph.D., executive vice president and president of Merck Research Laboratories, said he doesn't “know any anti-cytokine that has worked” in SSc-ILD.
“So this was a bold move to move that forward,” Li told analysts on the call. “It's a challenging and refractory disease.”
“When we publish that data, as you might imagine, we will look very carefully at the placebo arm,” he added. “If I see no progression in the placebo arm, the chances that I will be able to show benefit in a treatment arm becomes much more difficult.”
Merck reported the failure alongside news of the success of its phase 2b trial in HS, which hit its primary and key secondary endpoints. The drugmaker plans to share HS data at an upcoming medical meeting. In June, Merck reported a phase 3 victory for tulisokibart in ulcerative colitis (UC).
With hits in UC and HS, Merck still has a clear path to turning tulisokibart into a major product that could help offset the loss of exclusivity on Keytruda in 2028. But the failure in SSc-ILD nonetheless dents efforts to establish TL1A as a “node” for treating a wide range of diseases, as happened with TNF and IL-23. The broad clinical development program is designed to validate TL1A as a node in immunofibrosis.
“I would not throw out immunofibrosis based on the SSc-ILD study not reading out positive in the specific patient population we recruited,” Li said on the call.
The coming year could shed more light on Merck’s chances of delivering Li's vision. Merck is scheduled to publish phase 3 maintenance data in UC this year. Phase 2 trials in rheumatoid arthritis and radiographic axial spondyloarthritis have primary completion dates of next month and June 2027, respectively, per the federal trials database.