D3.438 - Clinical outcomes with navenibart according to baseline attack rate, body mass index, and age: results of the ALPHA-STAR trial

Hereditary angioedema (HAE) is characterized by recurrent, unpredictable swelling attacks associated with substantial disease burden. Patient characteristics such as body mass index (BMI) and age may influence attacks and treatment response. The objective of this post-hoc analysis was to assess potential differences in clinical outcomes (effectiveness, use of on-demand medication, and attack severity) between subgroups based on baseline attack rate, BMI, and age. 

ALPHA-STAR was a Phase 1b/2 trial in individuals with HAE-C1INH type 1 or 2 (NCT05695248). Twenty-nine participants were enrolled sequentially in 3 dose cohorts, pooled for this analysis. Post-hoc subgroups were determined based on baseline HAE activity (<2, 2 to <3, and ≥3 attacks per month; low, medium and high, respectively), age (<25, 25-44, 45-60, and >60 years), and BMI (18.5-24.9, 25-29.9, 30-34.9, >35-39.9, ≥40 kg/m2). Clinical outcomes included the overall change from baseline in monthly HAE attack rate, the rate of attacks treated with on-demand medication, and the rate of moderate or severe attacks. Data are reported as mean(median). 

Substantial reductions in HAE attack rates (attacks per month) were observed. Among participants with low baseline HAE activity (n=17), the attack rate decreased from a baseline of 1.32(1.43) to 0.19(0.15) post-treatment, with a change of -1.13(-1.03). In the medium group (n=6), the rate decreased from 2.43(2.37) to 0.21(0.00), with a change of -2.22 (-2.17). Among participants with high baseline HAE activity (n=6), the attack rate decreased from 4.60 (4.34) to 0.76 (0.67), a reduction of -3.84(-3.46). Reductions in attacks treated with on-demand medication followed a similar pattern, with changes of -0.86(-0.92), -1.36(-1.27), and -3.31(-2.93) in the low, medium and high baseline frequency groups, respectively. Post-treatment rates of moderate or severe attacks were also reduced across groups: 0.10 (0.00), 0.10 (0.00), and 0.29 (0.09), respectively. Consistent mean and median reductions in HAE attack rates were also observed across all age categories (<25 to >60 years) and BMI groups (<18.5 to >40 kg/m2). 

Treatment with navenibart resulted in reductions in HAE attack rates and on-demand medication use that were maintained for at least 6 months after the final dose. Consistency of attack rate reductions across baseline attack frequencies, age groups, and BMI supports navenibart as a potential long-acting therapeutic option for the broad HAE population.