Astria Therapeutics Begins Phase 3 Trial of Navenibart for Hereditary Angioedema

Astria Therapeutics, Inc., a biopharmaceutical company dedicated to creating life-altering treatments for allergic and immunologic conditions, has announced the start of the ALPHA-ORBIT Phase 3 clinical trial of navenibart. This trial focuses on individuals suffering from hereditary angioedema (HAE), a rare genetic disorder characterized by recurrent swelling episodes. Navenibart is designed to prevent these attacks with minimal treatment frequency, offering administration options every three months (Q3M) or every six months (Q6M).

Christopher Morabito, M.D., the Chief Medical Officer at Astria Therapeutics, expressed enthusiasm for the trial, emphasizing its potential to provide flexible treatment options, thereby reducing the burden on patients. The trial aims to demonstrate the effectiveness and safety of navenibart, allowing healthcare providers and patients the opportunity to choose the administration schedule that best suits their needs.

Dr. Aleena Banerji, a principal investigator for the ALPHA-ORBIT trial and Clinical Director of the MGH Allergy and Immunology Unit, highlighted the trial's significance. She noted the profound impact a therapy like navenibart could have, offering patients the chance to manage their condition with less frequent interventions and enabling them to live more freely.

The ALPHA-ORBIT trial is a global, randomized, double-blind, placebo-controlled Phase 3 study designed to evaluate navenibart’s efficacy and safety over a six-month period. It involves up to 135 adults and 10 adolescents with HAE Type 1 or Type 2. Adults in the study are randomly assigned to one of several dosage groups: an initial 600 mg followed by 300 mg Q3M, 600 mg Q6M, 600 mg Q3M, or placebo. Adolescents receive an initial 600 mg dose followed by 300 mg Q3M. This setup supports navenibart's potential to offer flexible dosing tailored to patient needs.

The primary endpoint of the trial is to measure time-normalized monthly HAE attacks at six months. A key secondary endpoint is assessing the proportion of participants who remain attack-free during this period. Preliminary results from the trial are expected by early 2027.

Upon completing the ALPHA-ORBIT trial, patients may qualify to participate in a long-term study called ORBIT-EXPANSE. In this follow-up, all participants will receive navenibart, with an adaptable dosing period designed to continue the patient-centered approach. Together, these trials aim to support global registration and approval of navenibart.

This Phase 3 program builds on promising results from earlier studies, particularly the Phase 1b/2 ALPHA-STAR trial. This trial demonstrated navenibart’s rapid onset of efficacy, favorable safety profile, and consistent inhibition of plasma kallikrein, a key factor in HAE. The study indicated a reduction of 90-95% in mean monthly attack rates and up to 67% of participants remaining attack-free over six months.

Navenibart is an investigational monoclonal antibody inhibitor of plasma kallikrein, currently in Phase 3 development for HAE treatment. The overarching goal is to provide patients with rapid and sustained attack prevention, giving them the opportunity to live a life unhampered by their condition.

Astria Therapeutics is committed to developing transformative therapies for those living with allergic and immunologic diseases. In addition to navenibart, their pipeline includes STAR-0310, a monoclonal antibody OX40 antagonist being developed for atopic dermatitis treatment. Through these programs, Astria aims to make a significant difference in the lives of patients and their families.