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Of 214 industry IBD trials terminated or withdrawn over two decades, only ~23% stopped for efficacy or safety.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We read the sponsor’s stated reason — the ClinicalTrials.gov whyStopped note — on all 214 terminated or withdrawn industry IBD trials.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.
Alnylam's two siRNA drugs hit the same liver target. One failed an FDA review in 2023. Two years later the other was approved for both forms of ATTR amyloidosis. The mechanism didn't change. The trial design did.
In September 2023 an FDA advisory committee voted 9-3 that patisiran's benefit supported approval for cardiac ATTR amyloidosis. The FDA rejected it anyway. Eighteen months later it approved vutrisiran — a near-identical Alnylam siRNA against the same liver target — for both forms of ATTR at once. Patisiran's APOLLO-B was 360 patients, 12 months, a six-minute-walk endpoint (+14.7 m, p=0.0162) with a secondary composite that missed at a win ratio of 1.27. Vutrisiran's HELIOS-B was 655 patients, up to 36 months, a hard mortality-plus-CV-events composite cut by 28%. Same mechanism, opposite verdicts — the molecule never changed, the trial did.
