Introduction
Etrasimod is an investigational, once-daily, oral, selective sphingosine 1‑phosphate (S1P)1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). In the ELEVATE UC 52 trial, primary and key secondary efficacy endpoints at Week 52 were evaluated among all patients randomised at baseline. The efficacy of etrasimod can be further characterised by evaluating efficacy endpoints at Week 52 among the subset of patients who met each efficacy endpoint at the end of the induction period (Week 12).
Aims & Methods
Here, we report proportions of patients receiving etrasimod that sustained induction efficacy endpoints at Week 52. In ELEVATE UC 52 (NCT03945188), patients (16–80 years) with moderately to severely active UC (defined as modified Mayo Score 4–9, endoscopic subscore ≥2 and rectal bleeding subscore [RBS] ≥1) were randomised 2:1 to once-daily etrasimod 2 mg or placebo. The ELEVATE UC 52 clinical trial comprised a 12-week induction period followed by a 40-week maintenance period with a treat-through design. This post hoc analysis assessed efficacy endpoints at Week 52 among the subset of patients who met the following efficacy endpoints at Week 12: clinical remission, endoscopic improvement, endoscopic improvement-histologic remission, symptomatic remission and RBS of 0.
Results
In ELEVATE UC 52, 81/289 (28.0%) patients treated with etrasimod achieved clinical remission at Week 12; of these, 66.7% (54/81) sustained clinical remission at Week 52 (Table). Among the 108/289 (37.4%) patients who achieved endoscopic improvement at Week 12, 72.2% (78/108) sustained the endpoint at Week 52; of 66/289 (22.8%) who achieved endoscopic improvement-histologic remission at Week 12, 63.6% (42/66) sustained the endpoint at Week 52; of 134/289 (46.4%) patients who achieved symptomatic remission at Week 12, 74.6% (100/134) sustained the endpoint at Week 52; of 166/289 (57.4%) patients who achieved an RBS of 0 at Week 12, 75.3% (125/166) sustained the endpoint at Week 52.
Table. Proportions of patients receiving etrasimod who sustained Week 12 induction efficacy endpoints at Week 52 (full analysis set)
|
|---|
| Maintained response at Week 52
| Loss of response/discontinued treatment
|
Clinical remissiona
n/N (%)
| 54/81 (66.7)
| 27/81 (33.3)
|
Endoscopic improvementb
n/N (%)
| 78/108 (72.2)
| 30/108 (27.8)
|
Endoscopic improvement-histologic remissionc
n/N (%)
| 42/66 (63.6)
| 24/66 (36.4)
|
Symptomatic remissiond
n/N (%)
| 100/134 (74.6)
| 34/134 (25.4)
|
RBS=0
n/N (%)
| 125/166 (75.3)
| 41/166 (24.7)
|
aClinical remission is defined as an SFS=0 (or =1 with a ≥1-point decrease from baseline), RBS=0 and ES ≤1 (excluding friability)
bEndoscopic improvement is defined as an ES ≤1 (excluding friability)
cEndoscopic improvement-histologic remission is defined as an ES ≤1 (excluding friability) with histologic remission measured by a Geboes Index score <2
dSymptomatic remission is defined as an SFS=0 (or =1 with a ≥1-point decrease from baseline) and RBS=0
ES, endoscopic subscore; RBS, rectal bleeding subscore; SFS, stool frequency subscore.
|
Conclusion
These findings suggest efficacy endpoints achieved at Week 12 were sustained by large proportions of etrasimod-treated patients at Week 52 based on both subjective and objective measures including clinical, endoscopic and histologic efficacy responses. Further analyses of larger samples sizes with longer follow-up are needed to evaluate long-term efficacy of etrasimod in patients with moderately to severely active UC.
Disclosure
BES: research/grants, e.g. Grant/Research Support: Arena, Janssen. Lecture fees/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda. Consultancy, Advisory Committee/Board Member: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D. Shareholder/Stock Options: Ventyx Biosciences. Other non-financial support: Janssen, Lilly, Pfizer, Takeda.
SV: grant/research support: AbbVie, MSD, Pfizer, Galapagos, Takeda; consultancy/advisory: AbbVie, AbolerIS, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson & Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts, Zealand; lecture/speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.
MCD: grant/research support: Janssen; consultancy: AbbVie, Arena, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, Trellus Health, UCB; shares/royalties: Trellus; directorship/ownership interests: Trellus.
BGF: consultant/on advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/Bristol-Myers Squibb, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco., Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen., Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared Ltd., Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.
RP: research support: AbbVie, Janssen, Takeda, Pfizer; consultancy: Abbott, AbbVie, Abivax, Alimentiv, Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus, Protagonist, Roche, Sandoz, Satisfai, Shire, Sublimity, Takeda, Theravance, Trellus, Viatris, Ventyx, UCB; speaker: AbbVie, Amgen, Arena, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda; member of advisory boards: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan, Organon, Pandion, Pfizer, Progenity, Protagonist, Roche, SandozShire, Sublimity, Takeda, Ventyx.
VJ: financial support: Celgene/Bristol-Myers Squibb, Pfizer, AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Takeda, Gilead and TiGenix; consultancy: AbbVie, Alimentiv, Amgen, Anokion, Applied Strategic, Arena, Asahi Kasei, Asieris, AstraZeneca, BIOJAMP, Celgene/Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, F Hoffmann La Roche, Flagship Pioneering, Fresenius Kabi, Fusion MD, Galapagos, Genentech, Gilead, GSK, Janssen, Knightslab, Organon, Landos, McKesson, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Prometheus, Protagonist, Reistone, Roche, Sandoz, Second Genome, Sorriso, Takeda, Teva, Topivert, Ventyx, Viatris, Vividion; lecture: AbbVie, Ferring, Galapagos, Janssen, Pfizer, Takeda, Bristol-Myers Squibb.
AJY: consultancy: Pfizer, Arena, Takeda, Bristol-Myers Squibb; lecture/speaker: Bristol-Myers Squibb.
MVC: grant support: Pfizer, Janssen, Novartis, Bristol-Myers Squibb; consultancy: AbbVie, Arena, Bristol-Myers Squibb, Medtronic, Pfizer, Prometheus, Eli Lilly, Janssen and Takeda; speaker: AbbVie, Janssen, Medtronic, Pfizer, Bristol-Myers Squibb, Takeda.
JP: personal: AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Revolo, Takeda, Theravance and Wassermann; grant support: AbbVie, Pfizer.
MG: employee & shareholder of Pfizer AG.
CJR, PS, JW: employees & shareholders of Pfizer.
SG: financial support/grants: GSK; speaker: Janssen, AbbVie, Pfizer, Takeda, Eli Lilly, Celltrion; advisory board: Janssen, AbbVie, Takeda, Pfizer, Bristol-Myers Squibb, Gilead, Galapagos, Ferring; Steering Committee member: Janssen, Bristol-Myers Squibb, AbbVie; Drug Monitoring Committee member: Janssen.
