Pivotal Phase 3 clinical trial of navenibart in HAE launched
Study to feature different dose arms to allow flexibility if therapy is approved
Astria Therapeutics has initiated a Phase 3 clinical trial to study its experimental therapy navenibart in adults and adolescents with hereditary angioedema (HAE).
The study, called ALPHA-ORBIT (NCT06842823), is planned to be pivotal, meaning, if the results are positive, the trial may serve as the basis to seek navenibart’s approval. Top-line results are expected in 2027.
“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,” Christopher Morabito, MD, Astria’s chief medical officer, said in a company press release.
HAE is a genetic disorder wherein abnormally high levels of the signaling molecule bradykinin trigger swelling attacks. Navenibart is an antibody-based therapy that’s designed to reduce bradykinin by blocking the activity of kallikrein, the enzyme responsible for producing it.
Aim of ALPHA-ORBIT is dosing options
The ALPHA-ORBIT study, which hasn’t started recruiting, is expected to enroll up to 135 adults and 10 adolescents with HAE types 1 and 2. The adults will be randomly assigned to either a placebo or navenibart at one of three different dosing schedules: 600 mg for the first dose and 300 mg every three months thereafter; 600 mg every six months; or 600 mg every three months. All the adolescents will be treated with navenibart (600 mg for the first dose, followed by 300 mg every three months). The therapy will be administered by injection under the skin, that is, subcutaneously.
Including different dose arms is designed to allow flexibility for patients if the therapy is approved.
“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 [two or four] times per year,” Morabito said.
ALPHA-ORBIT’s main goal will be to assess the impact of navenibart on rates of swelling attacks over six months. Participants who complete the study will be able to enroll in a long-term study called ORBIT-EXPANSE wherein all will be treated with navenibart. The long-term study will include a patient-centered flexible dosing period, according to Astria.
The design of the Phase 3 trial was based largely on data from the Phase 1/2 ALPHA-STAR trial (NCT05695248), which showed that navenibart could reduce the rates of monthly swelling attacks by up to 95%.
“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 Aleena Banerji, MD, a principal investigator for the ALPHA-ORBIT trial at Massachusetts General Hospital. “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.”
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