FDA review brings oral HAE attack treatment closer to approval
Decision on deucrictibant capsule expected by April 2027 after positive trial
Written by |
The U.S. Food and Drug Administration has accepted Pharvaris’ application seeking approval of the immediate-release (IR) formulation of deucrictibant as an oral, on-demand treatment for hereditary angioedema (HAE) swelling attacks.
The New Drug Application (NDA) includes data from the treatment of more than 1,300 HAE attacks across a broad clinical development program, including the global Phase 3 RAPIDe-3 trial (NCT06343779). In that study, the oral therapy provided rapid and sustained symptom relief through complete resolution of attacks and was well tolerated in participants ages 12 and older with HAE types 1 and 2 or HAE with normal C1 esterase inhibitor (C1-INH).
The FDA set April 23, 2027, as its target date for a decision.
FDA accepts application for oral HAE attack treatment
“After 10 years of dedicated effort by the team at Pharvaris, this FDA acceptance of deucrictibant IR’s NDA represents a major milestone in our journey to develop a differentiated therapy with the potential to improve the standard of care for people living with HAE,” Berndt Modig, Pharvaris’s CEO, said in a company press release.
HAE occurs when genetic changes disrupt systems that normally keep bradykinin activity under control. Bradykinin is a signaling molecule that causes fluid to leak from blood vessels into surrounding tissues, triggering recurrent swelling attacks. In the most common forms, HAE types 1 and 2, mutations impair the production or function of C1-INH, a protein that helps control the biological pathway that generates bradykinin. In HAE with normal C1-INH, sometimes called HAE type 3, C1-INH levels and activity are normal, but excess bradykinin activity still drives attacks.
Deucrictibant is being developed to treat attacks across these forms of HAE. It is an oral small molecule designed to block the bradykinin B2 receptor, the target through which bradykinin triggers blood vessel leakage and swelling. Unlike several currently available on-demand treatments that require injection, the IR formulation is an oral capsule designed to rapidly control attacks when they occur.
“Pharvaris has a deep scientific legacy in bradykinin B2 receptor antagonism, a clinically proven therapeutic approach for HAE attack treatment. By leveraging this trusted mechanism and its chemical properties, deucrictibant IR has the potential to be an oral on-demand medicine that addresses unmet needs of those living with HAE,” Modig said.
In a Phase 2 study, called RAPIDe-1 (NCT04618211), the IR formulation rapidly relieved symptoms and helped resolve swelling attacks and was generally well tolerated in adults with HAE type 1 or 2. Similar benefits continued to be observed with repeated use in a long-term extension study called RAPIDe-2 (NCT05396105).
RAPIDe-3 tested the IR capsule as an on-demand treatment in adults and adolescents diagnosed with HAE, including those with HAE type 3. Participants were assigned to treat one attack with 20 mg of deucrictibant and another with a placebo, allowing researchers to compare the two treatments within the same participants.
The main goal was to see how quickly symptom relief began, defined as a Patient Global Impression of Change (PGI-C) rating of at least “a little better” at two consecutive timepoints within 12 hours after treatment. According to the company, the study met that primary goal and all 11 secondary efficacy endpoints.
Phase 3 trial shows faster relief and attack resolution
According to data recently shared at a scientific conference, the median time to the onset of symptom relief was 1.28 hours with deucrictibant, compared with more than 12 hours with placebo.
Deucrictibant also brought attacks under control more quickly. The median time to the end of attack progression — the earliest point after treatment when all later symptom ratings remained stable or improved — was 17.47 minutes with deucrictibant versus 228.67 minutes, or about 3.8 hours, with placebo. This endpoint was reached within 12 hours in 92.8% of deucrictibant-treated attacks and 60.9% of placebo-treated attacks. Among the deucrictibant-treated attacks that reached this endpoint, 97.4% did so after a single capsule.
The median time to complete resolution of attack symptoms was 11.95 hours with deucrictibant treatment versus more than 48 hours with placebo. Overall, 93.2% of deucrictibant-treated attacks did not require conventional rescue treatment.
The treatment was generally well tolerated. No treatment-related serious adverse events were reported, and no participants discontinued treatment because of treatment-emergent adverse events.
“In clinical studies, treatment of HAE attacks with deucrictibant IR resulted in rapid time to onset of symptom relief and accelerated time to complete symptom resolution. With the build out of our commercial infrastructure already underway, Pharvaris is poised for a successful launch of deucrictibant IR, if approved,” Modig said.
Pharvaris is also developing an extended-release formulation of deucrictibant as a once-daily preventive treatment. That formulation is being evaluated in the pivotal Phase 3 CHAPTER-3 clinical trial (NCT06669754), with topline results expected later this year. In addition, the Phase 3 CREAATE trial (NCT07266805) is recruiting participants at sites in the U.S., Canada, Europe, and other global locations to test both formulations of deucrictibant in an estimated 32 adults with acquired angioedema (AAE) due to C1-inhibitor deficiency.
MARY GRACE BAYLOSIS
Please help me for my daily medicine for my HAE disease..