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Of 214 industry IBD trials terminated or withdrawn over two decades, only ~23% stopped for efficacy or safety.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We read the sponsor’s stated reason — the ClinicalTrials.gov whyStopped note — on all 214 terminated or withdrawn industry IBD trials.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.
Every approved IBD drug fights inflammation. None of them touch fibrosis. TL1A does both.
30% of Crohn's disease patients will need surgery within ten years of diagnosis - not because their drugs failed to control inflammation, but because no approved drug stops the scar tissue that narrows their bowel. TL1A is the first target that could change that. Here is the biology behind the $18 billion bet.
A biosimilar approved in 2016. Still shelved in 2026.
Sandoz's Erelzi received FDA approval in August 2016. Nearly a decade later, it still hasn't launched in the US - while the same drug has been selling in Europe since 2017. The patent cliff is set for 2029. An antitrust challenge was dismissed in February 2026 and is now on appeal.
Amgen got FDA approval for Amjevita in September 2016. It shipped its first US vial in January 2023. Six and a half years between approval and market entry - and nine more Humira biosimilars followed the same pattern. The gap between "approved" and "on sale" isn't a quirk of Humira. It's how biologics competition works.
