BOSTON -- Astria Therapeutics, Inc. (Nasdaq:ATXS), a biopharmaceutical company focused on developing life-changing therapies for allergic and immunologic diseases, announced the initiation of the ALPHA-ORBIT Phase 3 clinical trial of navenibart in people living with hereditary angioedema (HAE). Navenibart has the potential to provide rapid and sustained HAE attack prevention with a very low treatment burden and administration every 3 months (Q3M) and every 6 months (Q6M).

“We believe that navenibart will deliver strong efficacy, low treatment burden, and favorable safety and tolerability and we are thrilled to have initiated our Phase 3 ALPHA-ORBIT trial to support that vision,” said Christopher Morabito, M.D., Chief Medical Officer at Astria Therapeutics. “The Phase 3 program is designed to enable options, providing patients and physicians with the potential to decide what works best for them by administering navenibart only 2 or 4 times per year.”

“We understand from patients that it would be incredibly meaningful to have a therapy that would enable them to live their lives free from the limitations of HAE,” said Dr. Aleena Banerji, Clinical Director MGH Allergy and Immunology Unit, and a Principal Investigator for the ALPHA-ORBIT trial. “Navenibart has demonstrated the potential to prevent HAE attacks with infrequent dosing, which could allow patients the freedom to spend less time managing their disease.”

ALPHA-ORBIT is a global, randomized, double-blind, placebo-controlled Phase 3 pivotal clinical trial to evaluate the efficacy and safety of navenibart over a 6-month treatment period in up to 135 adults and 10 adolescents (open label), with HAE Type 1 or Type 2. Adult patients will be randomized to receive one of three navenibart dose arms: 1) an initial 600 mg dose followed by 300 mg Q3M, 2) 600 mg Q6M, 3) 600 mg Q3M, or placebo; adolescents will receive an initial 600 mg dose followed by 300 mg Q3M. The dose arms support the potential to provide patient-centered dosing flexibility to people with HAE. The primary endpoint is time-normalized monthly HAE attacks at 6 months, and a key secondary endpoint includes the proportion of participants who are attack-free at 6 months. Top-line results from the trial are anticipated in early 2027.

After 6 months, patients may be eligible to enter a long-term trial, called ORBIT-EXPANSE, in which all patients will be treated with navenibart and which includes a patient-centered flexible dosing period. The navenibart Phase 3 program consists of the ALPHA-ORBIT Phase 3 trial and ORBIT-EXPANSE long-term trial, which are designed to support registration globally.

The Phase 3 program was designed based on positive final top-line results from target enrollment in the Phase 1b/2 ALPHA-STAR trial of navenibart, which showed rapid onset of robust and durable efficacy, favorable safety and tolerability, and pharmacokinetics and pharmacodynamics consistent with sustained plasma kallikrein inhibition for both Q3M and Q6M administration. Final results included reduction in mean monthly attack rate of 90-95% and up to a 67% attack-free rate over 6 months.