Introduction
Mirikizumab (miri), a humanized IgG4 monoclonal antibody that selectively binds to interleukin-23 subunit p19, is approved for the treatment of 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. As SC injections can be associated with pain/discomfort and thus poor patient experience, an investigational 2-mL single injection delivering the same miri dose has been developed.
Aims & Methods
This phase 1 study (NCT06475729) aimed to assess the pharmacokinetic (PK) bioequivalence and safety of miri solution administered as one 2-ml injection compared with 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 endpoint was PK, assessed by 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). PK parameters were estimated using non-compartmental analysis. The secondary endpoint was safety, assessed by the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) among participants exposed to miri. Evaluating the impact of injection site location on PK was an exploratory endpoint.
Results
A total of 244 participants (mean age: 42.4 years; 55.3% female) received one 200 mg/2 ml injection and 240 (mean age: 42.7 years; 53.3% male) received two 100 mg/1 ml injections. Baseline characteristics were similar in both groups. The three primary PK parameters all fell within the bioequivalence range (geometric least-squares mean [GM] ratio: 0.800–1.250; see table). Results were generally consistent across injection site locations with no significant differences between them. 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%]). Injection-site reactions occurred in 5/244 [2.0%] of participants with one injection and 4/240 [1.7%] with two injections. No SAEs were reported in either group.
| 2 × 1-ml SC injections (100 mg/ml) citrate-free miri
| 1 × 2-ml SC injection (100 mg/ml) citrate-free miri
| GM ratio (90% confidence interval)
|
Cmax, µg/mL, GM
| 12.8 (n=238)
| 13.3 (n=243)
| 1.039 (0.9853, 1.0956)
|
AUC0–∞, µg × day/mL, GM
| 221 (n=238)
| 223 (n=243)
| 1.011 (0.9564, 1.0685)
|
AUC0–t, µg × day/mL, GM
| 216 (n=238)
| 218 (n=241)
| 1.011 (0.9568, 1.0678)
|
Conclusion
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 patient experience and treatment adherence.
Disclosure
YO, CDP, AUK, KT, PP, XZ: Employees and shareholders of Eli Lilly and Company.
EVL Jr: Consulted for Abivax, AbbVie, Astellas, Avalo, Biocon, Bristol-Myers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Merck, Morphic, Ono Pharma, Takeda, and TR1X Bio; received research support from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda; shareholder of Exact Sciences and Moderna.
GDH: Adviser and/or speaker for Abbvie, Alimentiv, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Galapagos, Glaxo Smith Kline, Immunic, Index Pharmaceuticals, Johnson and Johnson, Merck, Polpharm, Prometheus biosciences, Prometheus Laboratories, Procise diagnostics, Protagonist, Sandoz, Takeda, Tillotts, and Ventyx.
SBH: Received advisory board and/or consulting fees from Abbvie, Takeda, Janssen, Celltrion, Pfizer, GSK, Ferring, Novartis, Roche, Gilead, NeoPharm, Predicta Med, Galmed, Medial Earlysign, and Eli Lilly; stocks/options in Galmed, Evinature, PredictaMed and Alma Therapeutics; and research support from Abbvie, Takeda, Janssen, Celltrion, Pfizer, Medtronic & Galmed.
