(P031) LONG-TERM EFFICACY AND SAFETY OF MIRIKIZUMAB FOLLOWING 104 WEEKS OF CONTINUOUS TREATMENT FOR CROHN'S DISEASE: RESULTS FROM THE VIVID-2 OPEN-LABEL EXTENSION STUDY

Background: VIVID-2 (NCT04232553) is an ongoing open-label extension study evaluating the long-term efficacy and safety of mirikizumab (miri), a selective IL-23p19 monoclonal antibody, in patients with moderately-to-severely active Crohn’s disease (CD). We present results from patients randomized to miri in the Phase 3 study VIVID-1 (NCT03926130) who continued subcutaneous (SC) miri dosing into VIVID-2.

Methods: In VIVID-1, the miri group received induction therapy of miri 900 mg IV at weeks 0, 4, and 8, followed by miri 300 mg SC every 4 weeks. Patients achieving endoscopic response (≥50% reduction from baseline in Simple Endoscopic Score for Crohn’s Disease [SES-CD]) at Week (W)52 continued with the same SC dosing of miri in VIVID-2. Outcomes analyzed included endoscopic response, endoscopic remission (SES-CD ≤4 and ≥2-point reduction from baseline, with no subscore >1 in any individual variable) and clinical remission (Crohn’s Disease Activity Index [CDAI] < 150) following 104 weeks of continuous miri treatment since entry into VIVID-1.  Biologic Failure was defined as prior inadequate response, loss of response, or intolerance to biologic therapy. The cutoff date was 02AUG2024. Patients who entered VIVID-2 after 01AUG2023 were not included in this interim analysis. Safety was assessed from the first dose in VIVID-2 through the cutoff date. Discontinuations or missing data were handled using modified non-responder imputation (mNRI) and observed case (OC) approaches.

Results: Among the patients randomized to miri in VIVID-1 who continued into VIVID-2 on miri SC, at W104, 81.8%(mNRI)/87.6%(OC) maintained endoscopic response, 54.9%/58.7% achieved endoscopic remission, and 79.0%/84.7% achieved clinical remission by CDAI (Figure1A). At W104 endoscopic remission was maintained by 72.5%/78.6% of patients who were in endoscopic remission and gained by an additional 33.3%/35.4% of those not in endoscopic remission at W52 (Figure1B). At W104, clinical remission by CDAI was maintained by 86.9%/92.9% of patients who were in CDAI remission and gained by an additional 55.8%/60.8% of those not in CDAI remission at W52 (Figure1B). Results in patients with and without prior biologic failure were generally similar (Figure1C). Severe Treatment Emergent Adverse Events (TEAEs) were reported in 3.4% of patients, while 6.8% experienced serious AEs, and 0.8% discontinued treatment due to an AE (Table1).

Conclusion: These first results from the VIVID-2 extension study among VIVID-1 W52 endoscopic responders demonstrate long-term clinical and endoscopic efficacy of miri in patients with moderately-to-severely active CD. High maintenance rates of response and remission were observed after 2 years on miri therapy. Additionally, a meaningful number of patients gained remission in the second year. Overall, safety data were consistent with the known safety profile of miri.