P1139 - One Subcutaneous Injection of Mirikizumab Is Bioequivalent to 2 Subcutaneous Injections: Results from a Pharmacokinetic Comparability Study in Healthy Participants

Yuki Otani, ¹, Christopher Payne, ¹, Edward V.. Loftus, MD², Geert R. D’Haens, MD, PhD³, Shomron Ben Horin, ⁴, Abhishek Upadhya, ¹, Kristin Todd, ¹, Paola Pellanda, ¹, Xin Zhang, ¹
1Eli Lilly and Company, Indianapolis, IN; 2Mayo Clinic College of Medicine and Science and Mayo Clinic, Rochester, MN; 3Department of Gastroenterology, Amsterdam University Medical Center, Amsterdam, Noord-Holland, Netherlands; 4Sheba Medical Center, Tel-Hashomer, Affiliated with the Tel Aviv University, Tel Aviv, Tel Aviv, Israel

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 two 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 versus the commercially available two 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 two 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 (C_max), area under the concentration–time curve (AUC) from time zero to infinity (AUC_0–∞), and AUC from time zero to the last timepoint with measurable concentration (AUC_0–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% female) and 240 receiving two 1-mL injections (mean age: 42.7 years; 53.3% male), baseline characteristics were comparable. The three primary PK parameters all fell within the bioequivalence range (geometric least-squares mean [GM] ratio: 0.800–1.250; see table). Observed GM were consistent across injection site locations. TEAEs were reported in 48 participants with one injection (19.7%) and 55 with two injections (22.9%). Most TEAEs were mild (62/74 events with one injection [83.8%] vs 85/100 with two injections [85.0%]). No SAEs were reported in either group.

Discussion: Miri 200 mg administered as one 2-ml SC injection was bioequivalent to two 1-ml injections, and most TEAEs were mild. In clinical practice, reducing the number of injections may improve treatment adherence.


Figure: Summary of Pharmacokinetic Parameters

Disclosures:
Yuki Otani: Eli Lilly and Company – Employee, Stock Options.
Christopher Payne: Eli Lilly and Company – Employee, Stock Options.
Edward Loftus: AbbVie – Consultant, Grant/Research Support. Abivax – Consultant. Astellas – Consultant. Avalo – Consultant. Biocon – Consultant. Celltrion – Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Exact Sciences – Stock Options. Fresenius Kabi – Consultant. Genentech – Advisory Committee/Board Member. Gilead – Consultant, Grant/Research Support. Iota Biosciences – Consultant. Iterative Health – Consultant. Johnson & Johnson – Consultant, Grant/Research Support. Merck – Consultant, Grant/Research Support. Moderna – Stock Options. Morphic – Consultant. Ono Pharma – Consultant. Spyre – Advisory Committee/Board Member. Takeda – Consultant, Grant/Research Support. TR1X Bio – Consultant.
Geert D’Haens: Abbvie – Advisor or Review Panel Member, Speakers Bureau. Abivax – Advisor or Review Panel Member. Agomab – Advisor or Review Panel Member. Alimentiv – Advisor or Review Panel Member. AMT – Consultant. Anaptys Bio – Advisor or Review Panel Member. AstraZeneca – Consultant. Boehringer Ingelheim – Advisor or Review Panel Member. Bristol Myers Squibb – Advisor or Review Panel Member, Speakers Bureau. Celltrion – Advisor or Review Panel Member. Eli Lilly – Advisor or Review Panel Member. Exeliom – Consultant. Galapagos – Advisor or Review Panel Member. Glaxo Smith Kline – Advisor or Review Panel Member. Gossamerbio – Consultant. Immunic – Consultant. Index Pharmaceuticals – Advisor or Review Panel Member. Johnson & Johnson – Advisor or Review Panel Member. Kaleido – Consultant. Merck – Advisor or Review Panel Member. Origo – Consultant. Pfizer – Consultant, Speakers Bureau. Polpharm – Advisor or Review Panel Member. Procise Diagnostics – Consultant. Progenity – Consultant. Prometheus Biosciences – Advisor or Review Panel Member. Protagonist Therapeutics – Consultant. Sanofi – Advisor or Review Panel Member. Seres Health – Advisory Committee/Board Member. Takeda – Advisor or Review Panel Member. Tillotts – Advisor or Review Panel Member.
Shomron Ben Horin: Abbvie – Advisory Committee/Board Member, Consultant, Grant/Research Support. Alma Therapeutics – Stock Options. Celltrion – Advisory Committee/Board Member, Consultant, Grant/Research Support. Eli Lilly and Company – Advisory Committee/Board Member, Consultant. Evinature – Stock Options. Ferring – Advisory Committee/Board Member, Consultant. Galmed – Advisory Committee/Board Member, Consultant, Grant/Research Support, Stock Options. Gilead – Advisory Committee/Board Member, Consultant. GSK – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support. Medial Earlysign – Advisory Committee/Board Member, Consultant. Medtronic – Grant/Research Support. NeoPharm – Advisory Committee/Board Member, Consultant. Novartis – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support. Predicta Med – Advisory Committee/Board Member, Consultant. PredictaMed – Stock Options. Roche – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support.
Abhishek Upadhya: Eli Lilly and Company – Employee, Stock Options.
Kristin Todd: Eli Lilly and Company – Employee, Stock Options.
Paola Pellanda: Eli Lilly and Company – Employee, Stock Options.
Xin Zhang: Eli Lilly and Company – Employee, Stock Options.

Yuki Otani, ¹, Christopher Payne, ¹, Edward V.. Loftus, MD², Geert R. D’Haens, MD, PhD³, Shomron Ben Horin, ⁴, Abhishek Upadhya, ¹, Kristin Todd, ¹, Paola Pellanda, ¹, Xin Zhang, ¹. P1139 - One Subcutaneous Injection of Mirikizumab Is Bioequivalent to 2 Subcutaneous Injections: Results from a Pharmacokinetic Comparability Study in Healthy Participants, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.