D1.390 - Long-term safety and efficacy of navenibart in participants with hereditary angioedema (HAE): Initial combined results from ALPHA-STAR and ALPHA-SOLAR

Navenibart is a long-acting highly potent monoclonal antibody against plasma kallikrein. Clinical trial results to date demonstrate the potential of navenibart to reduce the frequency of HAE attacks when administered every 3 months (Q3M) and every 6 months (Q6M). Here, we report the initial combined results from ongoing multicenter trials, ALPHA-STAR (NCT05695248) and ALPHA-SOLAR (NCT06007677), evaluating the long-term safety and efficacy of navenibart in participants with HAE Type 1 and Type 2, in the target enrollment population.

Participants enrolled in ALPHA-SOLAR after completion of the follow-up period from the Phase 1b/2 ALPHA-STAR trial. At the initiation of ALPHA-SOLAR, participants received a 600 mg dose of navenibart and entered 1 of 2 dosing cohorts: Cohort A, 300 mg every 3 months and Cohort B, 600 mg day 28 and then 600 mg every 6 months. The primary endpoint is incidence of treatment emergent adverse events (TEAEs) with long-term use of navenibart; secondary endpoints include efficacy assessments. The baseline attack rate was assessed during the ALPHA-STAR trial. This analysis includes safety and efficacy results from the target enrollment population, and additional follow-up data will be presented.

Participants (n=16) had an average of 12.2 (8.3 - 17.6) months of treatment as of this data cut. TEAEs were seen in 15 participants (93.8%); four participants (25%) experienced related TEAEs. No new related TEAEs occurred in ALPHA-SOLAR. There were no severe or serious adverse events and no adverse events leading to discontinuation. The mean (median) pooled time-normalized HAE attack rate across ALPHA-STAR and ALPHA-SOLAR decreased from a baseline of 2.22 (2.02) to 0.29 (0.10) attacks per month, and 10 participants had ≥90% attack rate reductions across both trials. In ALPHA-SOLAR, Cohort A attack rate reduced from 2.46 (2.14) to 0.09 (0) per month and Cohort B reduced from 1.83 (1.74) to 0.32 (0.29) per month at last follow up. At month 6 in ALPHA-SOLAR, 9 (56%) participants were attack free. Pharmacokinetic and pharmacodynamic results were consistent with clinical results.

These data demonstrate that continued treatment with navenibart has a favorable safety profile and produces robust reduction of HAE attacks. Navenibart (Q3M and Q6M) is being evaluated in an ongoing Phase 3 trial (NCT06842823).