Navenibart Shows Promise in Reducing Hereditary Angioedema Attacks in Phase 1b/2 Trial

• Interim analysis of the ALPHA-STAR trial demonstrates navenibart's effectiveness in reducing hereditary angioedema attacks, with complete elimination of severe attacks at both 3- and 6-month follow-ups.
• The study showed significant reduction in monthly attack rates requiring rescue medication, from 1.86 to 0.16 at 3 months and 1.32 to 0.10 at 6 months post-treatment.
• The drug demonstrated a favorable safety profile with no serious treatment-emergent adverse events or discontinuations reported during the trial period.

The investigational drug navenibart has demonstrated promising efficacy in reducing the burden of hereditary angioedema (HAE) according to interim analysis results from the ongoing Phase 1b/2 ALPHA-STAR clinical trial. The findings were presented at the 2025 AAAAI/World Allergy Organization Joint Congress in San Diego by Dr. Joshua Jacobs, Medical Director of Allergy and Asthma Clinical Research.

Significant Reduction in Attack Frequency and Severity

The ALPHA-STAR trial (NCT05695248) enrolled 16 adult patients with HAE-C1INH Type 1 or Type 2, with a mean age of 46 years. The study design included three dose cohorts: 450 mg on day 1 (cohort 1), 600 mg on day 1 with 300 mg on day 84 (cohort 2), and 600 mg on days 1 and 28 (cohort 3).

At the three-month follow-up, involving 14 evaluable participants, the data showed remarkable improvements:

• Mild attacks decreased from 0.95 to 0.13 per month
• Moderate attacks reduced from 1.25 to 0.05 per month
• Severe attacks dropped from 0.11 to 0 per month

The six-month data, available for seven participants, maintained this positive trend:

• Mild attacks decreased from 0.45 to 0.10 per month
• Moderate attacks reduced from 1.54 to 0.08 per month
• Severe attacks were eliminated, dropping from 0.14 to 0 per month

Impact on Rescue Medication Use

One of the most significant findings was the substantial reduction in the need for rescue medication. The mean rate of HAE attacks requiring rescue medication decreased dramatically:

• From 1.86 to 0.16 attacks per month at 3 months
• From 1.32 to 0.10 attacks per month at 6 months

Safety Profile and Clinical Implications

The interim analysis revealed a favorable safety profile for navenibart, with no reports of serious treatment-emergent adverse events or patient discontinuations. This safety data, combined with the efficacy results, suggests that navenibart could potentially offer a new therapeutic option for HAE patients.

Dr. Jacobs and his research team emphasized that these results indicate navenibart's potential to significantly reduce the overall burden of HAE, as measured through multiple clinically relevant parameters including attack frequency, severity, and rescue medication use.