S1578 One Subcutaneous Injection of Mirikizumab Is Bioequivalent to 2 Subcutaneous Injections: Results From a Pharmacokinetic Comparability Study in Healthy Participants

Introduction: Mirikizumab (miri), a humanized IgG4 monoclonal antibody that selectively binds to interleukin-23 subunit p19, is approved for moderately to severely active ulcerative colitis and Crohn’s disease. In ulcerative colitis, maintenance treatment with 200 mg miri given as 2 1-mL subcutaneous (SC) injections every 4 weeks was efficacious and safe in the phase 3 maintenance LUCENT-2 and long-term extension LUCENT-3 trials. Given the pain/discomfort associated with SC injections, a single 2-mL injection delivering the same dose has been developed to enhance patient adherence. Methods: This phase 1 study evaluated the pharmacokinetic (PK) bioequivalence and safety of miri solution administered as one 2-ml injection vs the commercially available 2 1-ml injections. Healthy participants were stratified into weight categories (<75 kg, 75–85 kg, and >85 kg) and randomized (1:1) to receive one dose of 200 mg of SC citrate-free miri as either one (200 mg/2 mL) or 2 injections (each of 100 mg/1 mL) delivered by an autoinjector. Participants were sub-randomized (1:1:1) by injection site (arm, thigh, and abdomen). Blood samples were collected at pre-defined intervals up to 10 weeks post-dosing. The primary PK endpoints were the maximum observed concentration (Cmax), area under the concentration–time curve (AUC) from time zero to infinity (AUC0–∞), and AUC from time zero to the last timepoint with measurable concentration (AUC0–t). The secondary endpoint was safety [treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)]. Evaluating the impact of injection site location on PK was an exploratory endpoint. Results: Of 244 participants receiving one 2-mL injection (mean age: 42.4 years; 55.3% women) and 240 receiving 2 1-mL injections (mean age: 42.7 years; 53.3% male), baseline characteristics were comparable. The 3 primary PK parameters all fell within the bioequivalence range (geometric least-squares mean [GM] ratio: 0.800–1.250). Observed GM were consistent across injection site locations. TEAEs were reported in 48 participants with one injection (19.7%) and 55 with 2 injections (22.9%). Most TEAEs were mild (62/74 events with one injection [83.8%] vs 85/100 with 2 injections [85.0%]). No SAEs were reported in either group. Conclusion: Miri 200 mg administered as one 2-ml SC injection was bioequivalent to 2 1-ml injections, and most TEAEs were mild. In clinical practice, reducing the number of injections may improve treatment adherence.