Extended-release tablets shown to cut HAE swelling attacks by over 80%
Lasting benefits being seen with preventive therapy in late-stage trial
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Once-daily treatment with deucrictibant extended-release (XR) tablets reduced the frequency of swelling attacks among people with hereditary angioedema (HAE) by more than 80% compared with a placebo in a late-stage clinical trial.
Moreover, lasting benefits were seen for study participants with different types of the chronic genetic disease.
That’s according to top-line data, or the trial’s first results, announced by Pharvaris, the therapy’s developer, which reported that the pivotal Phase 3 CHAPTER-3 study (NCT06669754) met its main and secondary goals.
The global trial tested the oral treatment candidate in individuals with three forms of HAE. Among people with the more common HAE types 1 and 2, deucrictibant reduced attack frequency by more than 85%, the data showed.
The treatment’s protective benefits began during the first week of use and were maintained throughout the 24-week, or about six-month, study. All secondary efficacy goals were also met, with deucrictibant-treated participants showing reductions in attack rates relative to the study’s start and a higher proportion of participants remaining attack-free. Most side effects were mild or moderate, and no treatment-related serious adverse events were reported.
Pharvaris said it plans to use these findings to support applications seeking approval of deucrictibant XR as a preventive treatment for angioedema attacks. Regulatory submissions are expected to begin in the first half of 2027, the company said.
“People living with HAE have been waiting for a well-tolerated oral therapy with injectable-like efficacy; we believe deucrictibant XR can help address this unmet need,” Peng Lu, MD, PhD, president of Pharvaris, said in a company press release. “CHAPTER-3 showed statistically significant reductions in attack frequency, characterized by early and sustained protection, clinically meaningful improvements in health-related quality of life, and better HAE control.”
HAE is marked by recurrent episodes of swelling that can affect the skin, abdomen, face, and airways. HAE types 1 and 2, the most common forms, are caused by deficient or dysfunctional C1 inhibitor, a protein that normally helps regulate pathways leading to the production of bradykinin. Excessive bradykinin signaling causes blood vessels to become more permeable, allowing fluid to leak into nearby tissues and trigger swelling.
CHAPTER-3 trial tested deucrictibant in 3 HAE types
Deucrictibant is an oral small molecule designed to block the bradykinin B2 receptor, preventing bradykinin from exerting its effects. Pharvaris is developing two oral formulations: an extended-release tablet intended for long-term attack prevention, and an immediate-release (IR) capsule for treating attacks when they occur.
Earlier studies had shown that deucrictibant could reduce HAE attacks when taken preventively, and that its IR formulation could provide rapid symptom relief when used on demand.
CHAPTER-3 was designed to determine whether once-daily deucrictibant XR could safely prevent HAE attacks in adolescents and adults among people with HAE type 1, type 2, or HAE with normal C1 inhibitor. According to Pharvaris, it was the first Phase 3 preventive trial to involve all three HAE types.
The study enrolled 85 participants from 21 countries. In total, 55 participants received 40 milligrams (mg) of deucrictibant XR once daily for 24 weeks, while 30 received a placebo over the same time period. The study’s main goal was to compare monthly HAE attack rates between the two groups.
Participants given the placebo experienced a mean of 2.06 attacks per month, compared with 0.35 attacks per month among those receiving deucrictibant XR. This meant a significant 83% reduction in attack rate.
Among the 80 participants with HAE type 1 or type 2, deucrictibant reduced the mean monthly attack rate by 87% relative to the placebo. Pharvaris said the primary endpoint findings were generally consistent across the analyzed subgroups. Protection became apparent within the first week and persisted for the full six months of treatment, per the company.
Substantial reductions in attack frequency seen for all patients
Pharvaris reported substantial reductions in attack frequency from the beginning of the study, as well as an increase in the proportion of people who remained free of HAE attacks. Additionally, clinically meaningful improvements in health-related quality of life and overall HAE control were also observed, per the company.
Deucrictibant XR was generally well tolerated, the data showed. Most treatment-emergent adverse events were described as mild or moderate, and investigators reported no serious adverse events related to treatment. One participant receiving deucrictibant and one receiving placebo stopped treatment because of an adverse event.
“Deucrictibant could be the first and only oral therapy to offer injectable-like efficacy and a well-tolerated profile in on-demand treatment and prophylaxis with our two unique formulations,” said Berndt Modig, chief executive officer of Pharvaris.
The company said additional effectiveness and safety data from CHAPTER-3 will be presented at future medical meetings, along with patient experience results.
Deucrictibant is also being evaluated in the Phase 3 CREAATE (NCT07266805) study, slated to wrap up next year. That trial is testing the extended-release therapy for preventing attacks in people with acquired angioedema caused by C1 inhibitor deficiency.
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