Disease indication
The endoscope was part of the score from the start. And unlike its sibling disease, this one has an operation that can actually cure it.
Disease-modifying: Stop the inflammation eroding the colonic lining, judged on an endpoint that has never been purely symptomatic: the Mayo score has included direct visualisation of the mucosa as one of its four components since 1987. Seven distinct mechanisms have reached approval since 1998 — this site's most successful translational record.
Aminosalicylates, TNF, leukocyte-integrin trafficking, IL-12/23 (p40), IL-23 (p19), JAK, and S1P receptor modulation. Matches rheumatoid arthritis' count and exceeds Crohn's disease's five.
Two outright failures, and one — faecal microbiota transplantation — with genuine randomised-trial benefit that has never translated into an approved, labelled product.
The Mayo score's endoscopic subscore has been one of its four components since the instrument was first published — the objectivity Crohn's spent two decades bolting on was present here from the start.
An induction trial, then a re-randomised maintenance trial in responders — a design ulcerative colitis programmes have run since well before Crohn's needed an endoscopic co-primary to catch up.
Compare the founding year of this page's primary endpoint against Crohn's. The Mayo score has included an endoscopic component since it was first published in 1987 — the objectivity Crohn's spent two decades trying to bolt on afterward was built into this disease's endpoint from day one.
| Endpoint | Type | Read at | Standing |
|---|---|---|---|
| Full Mayo Score (Mayo Clinic Score) | Composite | 8–52 weeks | Accepted |
| Endoscopic remission (Mayo endoscopic subscore) | Imaging | 8–52 weeks | Accepted |
| Histologic remission | Laboratory | 8–52 weeks | Exploratory |
| Fecal calprotectin | Laboratory | 2–8 weeks | Surrogate |
| Colectomy-free survival | Clinician-rated | 1–5+ years | Exploratory |
Compare this matrix with Crohn's disease. The models are largely the same tools, but rated differently here: a chemical-injury model that under-represents transmural, ileal Crohn's is a genuinely closer match to mucosal, colon-restricted ulcerative colitis. Anatomy, not just immunology, changes what a model is good for.
| Model | FaceDoes it look like the disease? | ConstructDoes it arise the same way? | PredictiveHeal the mucosa |
|---|---|---|---|
Seven distinct mechanisms reached approval, matching rheumatoid arthritis and beating Crohn's disease's five. The most tractable indication on this site, and the endpoint story below is a large part of why.
| Intervention | Rested on | Primary endpoint | Reached | Outcome |
|---|---|---|---|---|
Mirikizumab Eli Lilly · Selective neutralisation of the interleukin-23 p19 subunit | IL-10 KO | Clinical remission on the full Mayo Score at week 12 (induction) and week 40 (maintenance) | Approved LUCENT-1 / LUCENT-2 · 2023 | Approved |
Ozanimod Bristol Myers Squibb · Sphingosine-1-phosphate receptor modulation, trapping lymphocytes in lymph nodes and reducing those available to traffic to the gut | T-cell transfer colitis | Clinical remission on the full Mayo Score at week 10 (induction) and week 52 (maintenance) | Approved True North · 2021 | Approved |
Etrolizumab Genentech · Blockade of the β7 integrin subunit, affecting both α4β7 and αEβ7 | T-cell transfer colitis | Clinical remission on the full Mayo Score, co-primary with endoscopic improvement | Phase 3 HICKORY / GARDENIA / LAUREL · 2020 | Failed |
Ustekinumab Janssen · Neutralisation of the shared p40 subunit of interleukin-12 and interleukin-23 | IL-10 KO | Clinical remission on the full Mayo Score at week 8 (induction) and week 44 (maintenance) | Approved UNIFI · 2019 | Approved |
Tofacitinib Pfizer · Pan-JAK inhibition, blocking intracellular signalling downstream of several inflammatory cytokines | IL-10 KO | Full Mayo Score remission at week 8 (induction) and week 52 (maintenance) | Approved OCTAVE Induction 1 / 2, OCTAVE Sustain · 2018 | Approved |
Faecal microbiota transplantation Investigator-led · Transfer of a donor's gut microbial community to restore microbial diversity and immune tolerance | Muc2 KOIL-10 KO | Clinical and endoscopic remission on the full Mayo Score | Phase 2/3, multiple trials 2017 | Benefit, no approval |
Vedolizumab Takeda · Blockade of α4β7 integrin, selectively disrupting leukocyte trafficking into the gut | T-cell transfer colitis | Clinical response on the full Mayo Score at week 6 (induction) and week 52 (maintenance) | Approved GEMINI 1 · 2014 | Approved |
Golimumab Janssen · Neutralisation of tumour necrosis factor | T-cell transfer colitis | Clinical response on the full Mayo Score at week 6 | Approved PURSUIT · 2013 | Approved |
Adalimumab Abbott · Neutralisation of tumour necrosis factor | T-cell transfer colitis | Full Mayo Score remission at week 8 and week 52 | Approved ULTRA 1 / ULTRA 2 · 2012 | Approved |
Alicaforsen Ionis / various · Antisense oligonucleotide against ICAM-1, delivered as a rectal enema to reduce leukocyte adhesion locally | DSS colitis | Clinical and endoscopic improvement in distal disease | Phase 3 2010 | Failed |
Infliximab Centocor · Neutralisation of tumour necrosis factor | T-cell transfer colitis | Clinical response on the full Mayo Score at week 8 | Approved ACT 1 / ACT 2 · 2005 | Approved |
Mesalamine (5-ASA) Multiple · Topical and luminal anti-inflammatory action within the colonic mucosa | DSS colitis | Full Mayo Score remission or response | Approved 1987 | Approved |
A four-part composite of stool frequency, rectal bleeding, endoscopic appearance, and physician global assessment
The instrument Crohn's disease spent two decades trying to become.
A common disease with an endpoint that was never purely symptomatic, so there is no equivalent of Crohn's steroid-era blind spot to correct for — the disease-modifying trial design has looked roughly the same since the 1980s.
An induction programme, then a re-randomised maintenance trial in responders, run to a year — a design this disease has used since before Crohn's needed an endoscopic co-primary to catch up. Costs slightly more per programme than Crohn's, and less per approval, because more of these programmes actually succeed.
693 patient-years against 233 for a symptomatic programme. Cost grows more slowly than exposure because the fixed enrolment cost of each participant — screening, baseline imaging — is paid once however long they are then followed. The goal, not the molecule, still sets the budget.
Citedenrolment, duration and study counts, from named trials.Assumptionthe two cost parameters below.Computedeverything else.
| Phase | Design | N × studies | Duration | Patient-years | Modelled cost |
|---|---|---|---|---|---|
| Phase 1 | SAD / MAD, healthy volunteers Reads: Safety, tolerability and pharmacokinetics Biologic, JAK and S1P mechanisms all carry their own monitoring requirements, so first-in-human work is not abbreviated. Conventional first-in-human designmoderate confidence | 50 | 9 mo | 38 | $1.4M–$2.2M |
| Phase 2 | Dose-ranging, full Mayo response Reads: Clinical response and endoscopic improvement on the full Mayo Score The endoscopic subscore is already part of the score being read at this phase — there is no separate 'early endoscopic signal' to bolt on, unlike the modern Crohn's Phase 2 design. OCTAVE, True North and LUCENT Phase 2 programmesmoderate confidence | 220 | 6 mo | 110 | $4.8M–$7.8M |
| Phase 3 · Induction | Two induction pivotals Reads: Clinical remission on the full Mayo Score at 8-12 weeks Sized after True North and LUCENT-1: two induction trials, both required to clear the bar before a patient enters maintenance. Sandborn et al., NEJM 2021 (True North); D'Haens et al., NEJM 2023 (LUCENT)moderate confidence | 450 × 2 | 3 mo | 225 | $15M–$24M |
| Phase 3 · Maintenance | Re-randomised maintenance trial in induction responders Reads: Clinical remission on the full Mayo Score at 44-52 weeks Only induction responders are re-randomised, so this trial enrols fewer patients than induction despite running four times as long. LUCENT-2 and True North maintenance designsmoderate confidence | 320 | 1 yr | 320 | $10M–$17M |
| Total | 2.5 yr of clinical development, treating phases as sequential | 693 | $32M–$51M |
Model assumptions, not citations — the only free parameters here. The fixed component covers screening, baseline imaging and randomisation, incurred once per participant; the running component covers visits, monitoring and site fees for each year on study. Splitting them matters: a single rate per patient-year would price short symptomatic trials far below what pivotal trials actually cost.
Calibration: priced this way a single pivotal trial in this programme comes to $5.0M–$8.0M, against published pivotal trial costs of $12–33M (median $19M) across all indications. A single symptomatic induction trial here is small and short by design, the same steroid-era logic as Crohn's — so it lands below the published range entirely. The range is set by the larger, longer biologic, JAK and S1P programmes below. Moore et al., JAMA Internal Medicine 2018.
Programme cost divided by a 16% likelihood of approval from Phase 1 in immune-mediated inflammatory disease (gastroenterology) — what one success costs once the failures are paid for. BIO / Informa / QLS, Clinical Development Success Rates — inflammatory bowel disease sits below the broader immunology average.
Read this one carefully: The same area-level rate used on the Crohn's disease page, nudged up slightly here: this page's ledger reached approval more often (nine of twelve disease-modifying attempts, against Crohn's seven of eleven), consistent with an endpoint that has been objective since 1987 rather than fixed midstream. A generic gastroenterology-wide rate may still understate this specific disease's odds.
These are portfolio figures spanning all of R&D and already carry the cost of failure, so they are not comparable with the per-programme clinical costs above — they are the order of magnitude those costs roll up into.
The remaining questions are about reading the endoscope more reliably and about whether a therapy with real trial evidence but no sponsor willing to file for it can ever become an approved drug.
Unlike Crohn's, this disease never lacked an objective component in its primary endpoint — the problem was that the endoscopic subscore was read locally and without blinding for decades. Central, blinded reading and more granular instruments such as UCEIS are the modern fix, refining an existing objective measure rather than bolting one on.
UCEIS (Travis et al., Gut 2012); central-reading methodology in modern IBD trials
With aminosalicylates, TNF, integrin, IL-12/23, IL-23-selective, JAK and S1P blockade all approved, the practical problem here increasingly resembles rheumatoid arthritis': matching mechanism to patient, not finding a mechanism that works at all.
Late-stage ulcerative colitis pipeline disclosures
Faecal microbiota transplantation has repeatedly shown benefit in randomised trials, yet donor variability, regulatory classification, and the difficulty of patenting a biological community have kept it from becoming an approved product. Defined bacterial consortia and live biotherapeutic products are attempts to engineer the same effect into something a sponsor can actually file for.
Live biotherapeutic product pipeline disclosures in ulcerative colitis