Several companies want to stretch IBD antibodies from a shot every few weeks to one every three months, or even six. Keeping the drug in the blood that long is the easy part. Whether the disease stays controlled right up to the next dose is the hard part, and the bet the newest programs are making.
“Long-acting” hides three claims: the drug stays in the blood (PK), keeps blocking its target (PD), and keeps the disease controlled (durability). Only the last proves a long interval works. Across 1,147 IBD trials, TL1A is the most crowded emerging target, with 7 antibodies, 6 sponsors and 36 trials, and 3 already in Phase 3. The leading long-acting candidates report 56–85 day half-lives, a 3–5× leap. But the trough, how much drug is left at the next dose, tells the real story: at the proposed quarterly and six-month intervals it sits at roughly 19–47% of peak, inside the range today’s biologics already tolerate. The PK was never the wall; durability is, and only XmAb942 is yet testing a long interval in patients.
Pfizer, Amgen, Lilly, Merck, and Astellas all failed at IGF-1R in cancer. Then a shelved Roche antibody became the only effective treatment for thyroid eye disease. Same receptor, completely different biology.
Five major pharmas spent two decades chasing IGF-1R as a cancer target. Every Phase 3 trial failed. The only IGF-1R drug ever approved is for thyroid eye disease — Tepezza, which generated $1.9 billion in 2024 and 8x exceeded its acquirer's peak forecast. Eleven more IGF-1R-for-TED programs are now in clinical trials, including the literal cancer-graveyard compound being resurrected by Sling Therapeutics. Targets don't travel. Disease context decides.
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.
How a quiet antibody program in the Netherlands became the highest-revenue drug in pharmaceutical history.
Keytruda was invented at Organon in the Netherlands, buried in two acquisitions, and became a $32B/year franchise across 20 cancer types. Nearly half of Merck's total revenue now depends on one molecule. Its US patent expires December 2028.
$6 billion in revenue. Generics launch May 2026. The decline already started.
Januvia was a $6 billion franchise for a decade. Generics launch in May 2026, but revenue is already down 64% from peak - squeezed by GLP-1 competition from above and generic anticipation from below.
