Astria’s Phase 3 trial of navenibart for HAE to launch soon
ALPHA-ORBIT will test 3 dosing regimens over 6 months
Astria Therapeutics is on track to start a Phase 3 clinical trial of navenibart, its therapy to prevent swelling attacks in people with hereditary angioedema (HAE), by March.
The trial, dubbed ALPHA-ORBIT, will test flexible dosing schedules, with navenibart being given every three months and every six months. Top-line results are expected in 2027.
“We are thrilled to announce our planned Phase 3 design, which reflects feedback from regulators and is intended to support global registration for both Q3M [every three months] and Q6M administration,” Jill C. Milne, PhD, Astria’s CEO, said in a company press release. “With navenibart, we are pioneering patient-centric dosing flexibility in HAE with the goal of maximizing attack rate reduction with a compellingly low burden of treatment. Assuming approval, we believe navenibart will become the market-leading, first-choice therapy for HAE.”
In HAE, swelling episodes are triggered by an overproduction of a signaling molecule called bradykinin.
Navenibart, also known as STAR-0215, is an antibody-based therapy that works by inhibiting kallikrein, the enzyme that mediates bradykinin’s production. By lowering bradykinin levels, the therapy is expected to reduce the frequency and severity of swelling attacks.
ALPHA-ORBIT to enroll up to 145 people with HAE type 1 or 2
In ALPHA-ORBIT, up to 145 people with HAE type 1 or 2 will be randomly assigned to a placebo or one of three dosing regimens of navenibart: an initial 600 mg dose followed by a 300 mg dose given every three months (group 1); a 600 mg dose given every six months (group 2); and a 600 mg dose given every three months (group three).
The study’s main goal is to assess the treatment’s ability to lower the number of monthly HAE attacks over the course of six months. The proportion of attack-free patients during that same period will also be determined as a key secondary goal.
Following the six-month treatment period, patients may enter a long-term extension study in which all will receive navenibart, with access to personalized dosing options.
The Phase 3 program, which includes ALPHA-ORBIT and the long-term extension study, were designed with insights from the U.S. Food and Drug Administration and the European Medicines Agency. Results from the clinical program are meant to support the therapy’s global regulatory approval.
“Our Phase 3 program was designed in collaboration with the patient community and physicians, is based on input from global regulatory authorities, and addresses the importance of providing options to patients for a disease that’s highly variable,” said Christopher Morabito, MD, Astria’s chief medical officer.
Its design builds on positive data from the Phase 1/2 ALPHA-STAR trial (NCT05695248), which demonstrated navenibart’s rapid and durable efficacy, and its favorable safety and pharmacological profile. In ALPHA-STAR, navenibart lowered mean monthly attack rates by 90%-95%, with up to 67% of the patients remaining attack-free over the course of six months.
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