Prometheus gave IBD its best shot at oncology-style patient selection: a companion diagnostic for its anti-TL1A drug, tulisokibart. Merck paid $10.8 billion, then built its Phase 3 trials to enroll everyone. The more crowded the anti-TL1A field gets, the stronger the case for a precision-medicine approach, even as the science has yet to deliver one.
Prometheus built a companion diagnostic to pick the ulcerative colitis patients its anti-TL1A antibody tulisokibart would help, and Merck bought the company for $10.8B. But when Merck launched the Phase 3 program in 2023 (soon after the acquisition), it chose to enroll everyone and demote the test to a secondary endpoint, a design choice fixed years before the trials read out. The now-positive Phase 3 confirms it, and the rest of the anti-TL1A class (Roche, Sanofi/Teva, Spyre, the newly-launched Bionyra) competes on potency and half-life, not patient selection. Yet the more crowded the field gets, the stronger the case for a precision-medicine approach, even as the science has yet to deliver it.
Of 214 industry IBD trials terminated or withdrawn over two decades, only ~23% stopped for efficacy or safety. The rest ran out of patients, money, or corporate priority — the trial failed, not the biology.
We read the sponsor’s stated reason — the ClinicalTrials.gov whyStopped note — on all 214 terminated or withdrawn industry IBD trials. Business and portfolio decisions are the single largest cause (36%); inability to enroll is next (22%). Lack of efficacy (20%) and safety (4%) together are only ~23% — so when an IBD trial is pulled early, ~77% of the time the reason says nothing about whether the drug worked.
Eleven years after approval, Entyvio remains the only IBD drug that acts only in the gut — and two large pharma programs have failed trying to replicate it.
Tysabri (natalizumab) blocks α4 integrin broadly — and 541 patients developed fatal brain infections. Entyvio (vedolizumab) blocks only α4β7, which binds MAdCAM-1 on gut endothelium. One Greek letter difference. Over a million patient-years, no REMS, no MRI surveillance. Takeda's $6 billion franchise is built on that subtraction — and on a head-to-head trial where vedolizumab beat Humira directly in ulcerative colitis.
