Data show sustained benefits of deucrictibant for HAE attacks
Extension findings confirm data from clinical trials
Treatment with deucrictibant continued to successfully prevent and treat swelling attacks in people with hereditary angioedema (HAE), according to new data from the open-label extension portions of two clinical trials.
The findings, presented at the Bradykinin Symposium held in Berlin Sept. 5-6, support the use of deucrictibant formulations for both prophylactic (preventive) and on-demand treatment of HAE, according to developer Pharvaris.
“The goal of HAE management is for affected individuals to live a normal life, ensuring they can engage in all work, school, family, and leisure activities as desired without limitation from angioedema symptoms,” Marc A. Reidl, MD, professor of medicine at the University of California San Diego, said in a company press release.
The data “provide evidence of the benefits of deucrictibant as a potential treatment for HAE, and highlight the importance of additional data from late-stage clinical development of deucrictibant in both treatment settings,” Reidl said.
Pharvaris is moving forward with Phase 3 clinical trials. The RAPIDe-3 study (NCT06343779) is testing an immediate-release formulation of deucrictibant, called PHVS416, as an on-demand therapy for HAE. Recruitment is ongoing at sites in the U.S., Puerto Rico, South Korea, and Germany.
Two formulations planned
Plans are also underway for a Phase 3 trial called CHAPTER-3 that will evaluate extended-release deucrictibant tablets as a prophylactic therapy in HAE patients, ages 12 and older.
The swelling attacks that characterize HAE are caused by the excess of a signaling molecule called bradykinin. Deucrictibant is an oral small molecule designed to block the bradykinin B2 receptor, a protein that bradykinin normally interacts with to exert its effects.
Deucrictibant prevents the downstream effects of bradykinin, and may be able to prevent HAE attacks and ease the severity of those that do arise.
Pharvaris is developing two formulations of the medication for these two purposes: an extended-release tablet for sustained attack prevention, and an immediate-release capsule for on-demand treatment.
The Phase 2 CHAPTER-1 trial (NCT05047185) is evaluating deucrictibant as a preventive therapy for HAE attacks. It enrolled 34 adults with HAE who were randomly assigned to receive oral deucrictibant (20 or 40 mg) or a placebo daily for 12 weeks, or about three months.
Patients were given the immediate-release formulation twice a day, intended as proof of concept for the once-daily, extended-release version that’s now being used.
Results showed that the treatment significantly reduced the rate of swelling attacks relative to a placebo. All 30 eligible participants who completed the main trial enrolled in an open-label extension period, during which all are receiving daily treatment with deucrictibant (40 mg/day).
The recently presented results covered data from this extension period, up to a cut-off of June 10, in which patients had been treated in the extension for a mean of just over a year.
Reductions in HAE attack rates that were observed in the main trial were sustained during the extension.
Attack rates were reduced by 93% after a year in the extension period relative to the start of CHAPTER-1, with a median monthly attack rate of zero for every month of the extension phase. On average, participants had fewer than one attack per year that required on-demand treatment and moderate-to-severe attack rates also 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.
Assessing on-demand efficacy
The Phase 2 RAPIDe-1 study (NCT04618211) was designed to assess the efficacy of deucrictibant immediate release capsules as an on-demand HAE treatment among 74 adult patients who were randomly assigned to receive the therapy at one of three doses (10 mg, 20 mg, or 30 mg) or a placebo.
Trial results showed deucrictibant was better than a placebo at easing pain and swelling in the skin, as well as abdominal pain, with a significantly faster time to symptom relief.
After RAPIDe-1, participants could enter the RAPIDe-2 (NCT05396105) long-term extension study, in which all would continue to receive deucrictibant as an on-demand therapy.
New efficacy analyses from 265 treated attacks in RAPIDe-2, with a cut-off date of March 1, showed the median time to onset of symptom relief was 1.1 hours, with nearly all (98.5%) of attacks starting to ease within 12 hours.
Reductions in attack severity were reached after a median of 2.6 hours, with 97.7% of attacks showing reduced severity by 12 hours.
Complete attack resolution was achieved after a median of 11.5 hours, with 85.8% of attacks completely resolving within 24 hours. More than 90% of the attacks that achieved that did so with only a single dose of immediate-release deucrictibant.
Findings from a separate analysis showed that outcomes with on-demand deucrictibant were more favorable than with attacks treated with standard of care in a separate observational study.
Lu said the findings from RAPIDe-2 “provide confidence in our ability to differentiate deucrictibant in the on-demand HAE space.”
Findings from both studies indicated that deucrictibant was well tolerated, with no new safety signals identified.
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