Deucrictibant Shows Sustained Benefits in Hereditary Angioedema Treatment
核心洞察
Data from open-label extensions of Phase 2 trials demonstrate deucrictibant's sustained efficacy in preventing and treating swelling attacks associated with hereditary angioedema (搜索) (HAE).
Results showed a 93% reduction in HAE attack rates after one year in the extension period, with a median monthly attack rate of zero.
Pharvaris is advancing deucrictibant with Phase 3 trials for both on-demand (RAPIDe-3) and prophylactic (CHAPTER-3) treatment of HAE, and exploring its potential in acquired angioedema (搜索).
Pharvaris' deucrictibant continues to show promise in both preventing and treating swelling attacks in individuals with hereditary angioedema (搜索) (HAE), according to recent data presented at the Bradykinin Symposium. The data, derived from open-label extension portions of two clinical trials, support the potential of deucrictibant formulations for both prophylactic and on-demand treatment strategies.
Sustained Efficacy in HAE Attack Reduction
Long-term data from the Phase 2 CHAPTER-1 trial demonstrated that reductions in HAE attack rates observed during the main trial were sustained throughout the extension period. After one year, attack rates were reduced by 93% relative to the start of CHAPTER-1, with a median monthly attack rate of zero. Participants experienced fewer than one attack per year requiring on-demand treatment, and moderate-to-severe attack rates remained low.
"These data underscore the potential of deucrictibant to be an effective and well-tolerated prophylactic agent in the treatment of HAE," said Peng Lu, MD, PhD, chief medical officer of Pharvaris.
Rapid Symptom Relief in On-Demand Treatment
Efficacy analyses from the RAPIDe-2 long-term extension study, involving 265 treated attacks, revealed a median time to onset of symptom relief of 1.1 hours. Nearly all attacks (98.5%) showed initial relief within 12 hours. Reductions in attack severity were observed after a median of 2.6 hours, with 97.7% of attacks showing reduced severity by 12 hours. Complete attack resolution occurred after a median of 11.5 hours, with 85.8% of attacks resolving within 24 hours, often with a single dose of immediate-release deucrictibant.
Advancing to Phase 3 Trials
Pharvaris is moving forward with Phase 3 clinical trials for deucrictibant. The RAPIDe-3 study (NCT06343779) is currently recruiting participants to evaluate an immediate-release formulation of deucrictibant (PHVS416) as an on-demand therapy for HAE. Additionally, plans are underway for the CHAPTER-3 trial, which will assess extended-release deucrictibant tablets as a prophylactic therapy in HAE patients aged 12 and older.
Mechanism of Action and Formulations
HAE swelling attacks are driven by an excess of bradykinin. Deucrictibant, an oral small molecule, functions by blocking the bradykinin B2 receptor (搜索), thereby preventing bradykinin from exerting its effects. Pharvaris is developing both an extended-release tablet for sustained prevention and an immediate-release capsule for on-demand treatment.
Exploring Acquired Angioedema
Building on promising data from a small study in Amsterdam, Pharvaris intends to explore the clinical development of deucrictibant in acquired angioedema (搜索), addressing an unmet need for specifically approved therapies. "There is an unmet need for therapies approved specifically for the treatment of [acquired angioedema],” said Remy S. Petersen, MD, researcher at the Amsterdam University Medical Center.
Berndt Modig, Pharvaris’ CEO, stated, “Given the totality of data for deucrictibant, now bolstered by new data from ongoing long-term extension studies showing tolerability and efficacy in both prophylaxis and on-demand treatment, we believe deucrictibant has the potential to become a preferred therapy for the management of HAE.”