The mannan-binding, lectin-associated serine protease-3 inhibitor OMS906 is well tolerated and leads to no safety concerns in healthy volunteers, according to the results of a phase 1 clinical trial presented at the 64th ASH Annual Meeting and Exposition.

These findings support the further clinical study of OMS906, including in patients with paroxysmal nocturnal hemoglobinuria (PNH), the authors said.

The investigators also reported that the pharmacokinetic and pharmacodynamic profiles of OMS906 showed predictable systemic exposure, evidence of alternative pathway inhibition, and a long duration of action. 

Finally, they reported no treatment-emergent serious adverse events.

Read more about the epidemiology of PNH

During this first-in-human, randomized, double-blind, single-center, placebo-controlled phase 1 clinical trial, healthy volunteers, aged 20 to 63 years, received single ascending doses of OMS906 between 0.1 and 5 mg/kg intravenously or 3 to 8 mg/kg subcutaneously. 

The primary outcome measures were the safety and tolerability of OMS906. Secondary outcome measures were the pharmacokinetics and pharmacodynamics of OMS906 and the formation of antidrug antibodies. 

Seventy-two participants of different ethnic backgrounds enrolled in the study. Of these, 54 received OMS906 and 18 received a placebo. 

Most treatment-emergent adverse events were mild and consisted of injection site reactions.  

The half-life of OMS906 was 103 to 423 hours. Measurable concentrations were detected at day 85 for the 5 mg/kg intravenous and 8 mg/kg subcutaneous doses. The key pharmacodynamic marker showed a dose-proportional response with rapid, substantial, and long-term suppression.

Antidrug antibodies were detected at a rate consistent with what is reported for other monoclonal antibodies in development, and there was no evidence of neutralizing activity.

Mannan-binding, lectin-associated serine protease-3 is the activator of complement factor D, which drives the formation of alternative pathway C3 convertase, generating C3b. This creates a positive feedback loop of protease complexes, leading to the inflammation, tissue destruction, and hemolysis that is seen in PNH.

Reference

Pullman W, Humphreys J, Philpot E, Cummings WJ. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the alternative pathway Masp-3 inhibitor OMS906 in a phase 1 study of healthy subjects. 64th ASH Annual Meeting and Exposition. New Orleans, LA, December 10-13, 2022. Poster number 2570.