Astria Therapeutics, Inc. announces positive preliminary results from the Phase 1a clinical trial of STAR-0215 in healthy subjects establishing early proof of concept of STAR-0215 as a potential long-acting preventative treatment for HAE. STAR-0215 was well-tolerated at all doses studied. The results showed rapid and sustained drug levels consistent with clinical benefit and sustained target engagement with plasma kallikrein inhibition for at least three months, supporting the potential for STAR-0215 to be dosed once every three months or less frequently. Astria plans to initiate the ALPHA-STAR Phase 1b/2 trial in HAE patients in Q1 2023.
“These results mark a significant milestone for STAR-0215 and Astria. We are excited that STAR-0215 has shown early proof of concept for its target profile: of being a long-acting preventative therapy for HAE, with a best-in-class PK profile, and dosing once every 3 months or less frequently,” says Jill C. Milne, Ph.D., CEO at Astria. “We aim to change the way those affected by HAE live with their disease and see these preliminary results as a critical step bringing us closer to improving patients’ lives. We are looking forward to bringing STAR-0215 to patients in the ALPHA-STAR trial early next year.”
“Patients want treatment options that can normalize their lives. I am pleased to see STAR-0215 moving forward in clinical development to patients,” says William Lumry, M.D., Founder and Medical Director of the AARA Research Center. “We understand the need from the HAE community for an effective treatment with less burdensome dosing administration and are excited to see that potential in STAR-0215.”
STAR-0215 is a monoclonal antibody inhibitor of plasma kallikrein designed to provide long-acting, effective HAE attack prevention. The Phase 1a randomized, double-blind, placebo-controlled single ascending dose trial of STAR-0215 evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of STAR-0215 at a single U.S. center. Twenty-five healthy adult subjects each received a single subcutaneous administration of one of three dose levels of 100mg, 300mg, or 600mg of STAR-0215 or placebo, and subjects are being followed for safety, PK, and PD for a total of 224 days. Preliminary data includes safety through 84 days for all three cohorts, PK and PD for the 100 mg and 300 mg cohorts through 84 days and PK and PD through 56 days for the 600 mg cohort.
Blinded safety results showed that STAR-0215 was well-tolerated at all dose levels. The most common treatment-related adverse event was mild (Grade 1), self-resolving injection site reaction, which most commonly was site redness. There were no clinically relevant changes in liver enzymes or coagulation parameters, serious adverse events or discontinuations. In the 300 and 600 mg dose groups, PK and PD results were consistent with clinical benefit up to three months, with an estimated half-life of STAR-0215 up to 110 days. Rapid and sustained drug levels consistent with clinical benefit support the potential for dosing STAR-0215 once every three months or less frequently. PD results showed rapid and robust target engagement with plasma kallikrein inhibition through at least three months with a single dose of STAR-0215. The levels of inhibition, 40 to 60% decrease in FXIIa-activated cleaved high molecular weight kininogen, are consistent with the levels shown to prevent attacks in people living with HAE.
The results support advancing STAR-0215 to a Phase 1b/2 trial, ALPHA-STAR, expected to initiate in Q1 2023. This global, multi-center, open-label, single and multiple dose proof-of-concept clinical trial in people with HAE, will evaluate safety, tolerability, HAE attack rate, PK, PD, and quality of life in patients. Initial results are expected from the single and multiple dose cohorts in mid-2024. The results from the Phase 1a trial also suggest that there could be an opportunity to dose STAR-0215 less frequently. Astria plans to evaluate the potential for 6-month dosing with additional healthy subject cohorts in the Phase 1a trial starting in Q1 2023 with initial results expected in Q4 2023.