D2.326 - Long-Term Safety and Efficacy of Oral Deucrictibant for Prophylaxis in Hereditary Angioedema: Data Snapshot Results of the CHAPTER-1 Open-Label Extension Study

Deucrictibant is a selective, orally administered bradykinin B2 receptor antagonist under development for prophylactic and on-demand treatment of hereditary angioedema (HAE) attacks. The two-part, Phase 2 CHAPTER-1 study (NCT05047185) evaluates the efficacy and safety of deucrictibant for long-term prophylaxis of HAE attacks. The randomized, double-blind, placebo-controlled trial period (part 1) is complete, and an open-label extension (OLE; part 2) is ongoing. In part 1, deucrictibant 40 mg/day reduced the attack rate by 84.5% (P=0.0008) vs placebo during 12 weeks of treatment, and the treatment was well tolerated.

CHAPTER-1 enrolled 34 participants who were aged ≥18 and ≤75 years, diagnosed with HAE-1/2, and had experienced either ≥3 attacks within 3 months prior to screening or ≥2 attacks during screening (up to 8 weeks). Thirty participants completed part 1, during which they received deucrictibant 20 mg/day (n=11), 40 mg/day (n=10), or placebo (n=9) for 12 weeks. All thirty participants continued into the OLE and received treatment with deucrictibant 40 mg/day.

This data snapshot (cutoff: 10 June 2024) included 30 participants who received deucrictibant 40 mg/day for a mean duration of 12.8 months (maximum _~20 months) in the OLE. Participants were 60% female and had a mean age of 39.1 years at part 1 study baseline. The safety analysis showed no treatment-related serious treatment emergent adverse events (TEAEs), no TEAEs leading to study drug discontinuation, and that deucrictibant was well tolerated. At study baseline, participants had a mean (standard deviation) attack rate of 2.18 (1.35) and a least squares mean (LSM) attack rate of 0.15 (standard error [SE] 0.05) in the OLE. Attack rate in the OLE was low irrespective of participants’ attack rate at study baseline; 0.10 and 0.19 for participants with ≥1 to <2 attacks/month and ≥2 attacks/month at study baseline, respectively. During the OLE, the LSM (SE) rates of “moderate and severe” attacks and attacks treated with on-demand medication were 0.07 (0.03) and 0.07 (0.02), respectively. The median proportion of days with HAE symptoms in the OLE was 0.0%.

These data from the ongoing CHAPTER-1 OLE extend the findings of part 1 and provide additional evidence on the long-term safety and efficacy of deucrictibant treatment for prophylaxis of HAE attacks.