STAR-0215, a humanized immunoglobulin G1 (IgG1) antibody, is a potential new agent for long-term prophylaxis for hereditary angioedema (HAE).
The treatment is predicted to be active in patients for at least 3 months, according to minimal physiologically based pharmacokinetic model simulations published in the Journal of Pharmacology and Experimental Therapeutics.
“The use of plasma kallikrein inhibitors for preventative therapy has demonstrated that both the potency of plasma kallikrein inhibition and the long duration of action are key drivers for suppression of HAE attacks,” the authors wrote. “The present study describes the generation and functional characterization of STAR-0215, a novel, potent, and selective long-acting plasma kallikrein antibody inhibitor with the potential to prevent attacks more completely and with less frequent administration.”
The research team generated the STAR-0215 monoclonal antibody from hybridoma mouse cell lines demonstrating preferential binding to active plasma kallikrein. The cells were obtained from prekallikrein knockout mice immunized with active human plasma kallikrein.
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STAR-0215 is selective for the active enzyme and resists binding to the prekallikrien proenzyme, thereby preventing the unwanted target-mediated clearance due to high circulating levels of prekallikrein.
In this way, more STAR-0215 is available to suppress the enzyme activity during HAE attacks, and for a longer duration.
Simulation data indicate that STAR-0215 could represent an improvement on existing prophylactic treatments in terms of efficacy and the dosing regimen. Currently approved treatments require daily oral dosing (berotralstat), injections every 3 to 4 days (plasma-derived C1-INH), or injections every 2 weeks (lanadelumab).
A phase 1 study on STAR-0215 in healthy human participants is underway. Given that the plasma contact system plays a role in various other diseases, including diabetic retinopathy and cerebrovascular disease, the authors hypothesize that STAR-0215 may have additional potential indications.
Bedian V, Biris N, Omer C, et al. STAR-0215 is a novel, long-acting monoclonal antibody inhibitor of plasma kallikrein for the potential treatment of hereditary angioedema. J Pharmacol Exp Ther. Published online August 29, 2023. doi:10.1124/jpet.123.001740