Astria Therapeutics announced positive final results from its ALPHA-STAR Phase 1b/2 clinical trial, evaluating navenibart (STAR-0215) for hereditary angioedema (HAE). The trial, involving 16 patients, demonstrated a 90-95% reduction in the mean monthly attack rate over six months, supporting both every three-month (Q3M) and every six-month (Q6M) dosing regimens. These findings suggest navenibart could become a leading preventative therapy for HAE.
The ALPHA-STAR trial was a dose-ranging, proof-of-concept study in adults with HAE Type 1 or 2. It assessed the safety, tolerability, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and quality of life with single and multiple doses of navenibart, administered subcutaneously. The study included an eight-week run-in period to establish baseline HAE attack frequency. Efficacy, safety, PK, and PD were then evaluated for six months after the last dose.
Key Efficacy Results
- Cohort 1 (450 mg dose, n=4): 91% reduction in monthly attack rate, 96% reduction in moderate and severe attacks, 94% reduction in acute rescue medication use. 50% of patients were attack-free through 3 months, and 25% through 6 months.
- Cohort 2 (600 mg followed by 300 mg after 3 months, n=6): 95% reduction in monthly attack rate, 95% reduction in moderate and severe attacks, 94% reduction in acute rescue medication use, and 67% of patients attack-free.
- Cohort 3 (600 mg followed by 600 mg after 1 month, n=6): 92% reduction in monthly attack rate, 96% reduction in moderate and severe attacks, 91% reduction in acute rescue medication use, and 67% of patients attack-free.
Christopher Morabito, M.D., Chief Medical Officer at Astria Therapeutics, stated, "The results from the ALPHA-STAR Phase 1b/2 trial affirm our belief in navenibart’s profile and its potential to be a life-changing, market-leading preventative treatment for HAE patients." He highlighted the rapid onset, robust and durable efficacy, and favorable safety and tolerability observed with infrequent dosing.
Safety and Tolerability
Navenibart was generally well-tolerated, with no serious treatment-emergent adverse events (TEAEs) or discontinuations reported. Four non-severe, quickly resolved treatment-related TEAEs occurred: one case of dizziness, a transient injection site reaction (rash), injection site erythema, and injection site pruritus. No injection site pain was reported.
Next Steps
All 16 patients have enrolled in ALPHA-SOLAR, a long-term open-label trial. Initial safety and efficacy data from Q3M and Q6M dosing in ALPHA-SOLAR are expected in mid-2025. Pending regulatory feedback, Astria plans to initiate a Phase 3 program in Q1 2025, with topline results anticipated by year-end 2026.
Dr. Aleena Banerji, Clinical Director MGH Allergy and Clinical Immunology Unit, commented, "These results from the ALPHA-STAR trial are exciting for the future of the HAE treatment landscape. I am optimistic that a therapy with infrequent dosing, a well-tolerated profile, and a trusted mechanism and modality could alleviate the burden for patients."
