DV0012 study (NCT06511076): establish bioequivalence of zilucoplan pharmacokinetics (PK) after a single subcutaneous injection with zilucoplan pre-filled auto-injector pen (ZLP-AI) and pre-filled syringe (ZLP-PFS) in healthy volunteers. DV0013 study (NCT06471361): evaluate effectiveness and safety of ZLP-AI self-administration in patients with generalized myasthenia gravis (gMG).

Zilucoplan is a potent complement component 5 inhibitor approved for treatment of gMG, self-administered as a PFS. ZLP-AI may facilitate drug administration.

DV0012 was a Phase 1, open-label, single-center, two-period crossover study in healthy adult volunteers randomized 1:1 to one of two treatment sequences: single injection with ZLP-AI then ZLP-PFS, or ZLP-PFS then ZLP-AI. Primary PK parameters estimated were area under the curve (AUC), AUC up to last quantifiable concentration (AUC_0–t) and maximum observed concentration (C_max). DV0013 was a Phase 3b, open-label, multicenter study, in patients with gMG either participating in RAISE-XT (NCT04225871) or receiving commercially administered zilucoplan; patients self-administered once-daily ZLP-AI. Primary objective was the effective ZLP-AI self-administration through Day 14, defined as investigator-confirmed complete dose delivery. Satisfaction with self-injection, measured by the Self-Injection Assessment Questionnaire (SIAQ, domain scores 0–10) and safety were also assessed.

In DV0012 (N=14), the ratios of geometric least-squares means (90% confidence interval [CI]) for ZLP-AI:ZLP-PFS were 0.98 (0.95, 1.01), 0.98 (0.95, 1.01) and 1.00 (0.96, 1.04) for AUC, AUC_0–t and C_max, respectively. In DV0013 (N=31), complete dose delivery was achieved for 99.8% (95% CI: 98.8, 100) of ZLP-AIs. Treatment-emergent adverse events were reported by 22.6% (n/N=7/31) of patients; all were mild and non-serious. At Day 14, median (range) “satisfaction with self-injection” SIAQ domain score was 8.9 (6–10).

Zilucoplan bioequivalence was established in healthy volunteers between ZLP-AI and ZLP-PFS. Self-administration with ZLP-AI achieved high complete dose delivery and self-injection satisfaction, and was well-tolerated in patients with gMG, suggesting that ZLP-AI is an effective alternative for zilucoplan administration.