Pharvaris to seek FDA approval of HAE treatment deucrictibant
Company expects Phase 3 trial results this year
Pharvaris expects to ask the U.S. Food and Drug Administration to approve deucrictibant as an on-demand treatment for hereditary angioedema (HAE) attacks next year.
The application will cover the immediate-release (IR) capsule formulation of the therapy, which is intended to control swelling attacks as they occur.
The submission is pending the announcement of positive data from RAPIDe-3 (NCT06343779), a Phase 3 trial that’s assessing the safety and efficacy of deucrictibant as an on-demand treatment for swelling attacks in adults and adolescents with HAE. Topline results from the trial are expected in the fourth quarter of this year, Pharvaris said.
“The attack data in RAPIDe-3 have continued to accrue following the achievement of target enrollment in the study,” Berndt Modig, CEO of Pharvaris, said in a company press release. “Our phase 3 data may provide evidence of deucrictibant IR’s potential to address the desire of people living with HAE for an on-demand therapy that combines efficacy — from rapid end of progression to fast and complete resolution — and a favorable safety profile, with the convenience of a single-capsule oral dose.”
In HAE, genetic mutations lead to the overproduction of the signaling molecule bradykinin, which normally helps regulate blood pressure and inflammation. At high levels, bradykinin may cause blood vessels to leak fluid into nearby tissues, leading to the swelling attacks that characterize HAE. These can be particularly dangerous when they occur in the voice box (larynx), where swelling can block the airways and impair breathing.
Blocking receptor to prevent swelling
Elevated bradykinin is a feature of the three main types of HAE. Types 1 and 2 are caused by mutations in the SERPING1 gene that impair the production or function of C1 esterase inhibitor (C1-INH), a protein that helps regulate bradykinin production. Mutations that occur in genes other than SERPING1 and don’t affect C1-INH levels or function are the cause of HAE type 3, or HAE with normal C1-INH.
Deucrictibant, which has potential applicability across HAE types, aims to reduce blood vessel leakage, bringing down swelling. It does so by blocking the B2 bradykinin receptor, effectively preventing bradykinin from interacting with it and triggering swelling. The IR capsule formulation is designed to rapidly initiate B2 blocking to quickly curb swelling during an attack.
In a Phase 2 trial called RAPIDe-1 (NCT04618211), the therapy’s IR formulation safely and effectively treated swelling attacks in adults with HAE type 1 or 2. Participants began to see their symptoms ease about two hours after taking the medication. In a comparison group in which patients were taking a placebo, symptoms began to ease after about eight hours.
Deucrictibant continued to provide rapid symptom relief in a long-term extension study called RAPIDe-2 (NCT05396105).
“We aim to confirm the findings from our Phase 2 studies in a larger Phase 3 trial, RAPIDe-3,” said Peng Lu, MD, PhD, Pharvaris’ chief medical officer.
RAPIDe-3 will enroll an estimated 120 participants with HAE type 1, 2, or 3. Each participant will take deucrictibant during an attack and a placebo during another. For each attack, participants will evaluate their symptoms from before taking the medication until 12 hours after treatment. In RAPIDe-3, participants may also use treatment during non-severe swelling attacks occurring in the larynx.
Researchers will assess the time to onset of symptom relief, defined as the time between participants taking the treatment and consistently rating their symptoms at least “a little better” according to the Patient Global Impression of Change (PGI-C). Other outcome metrics will include the time to end of attack progression, defined as the earliest timepoint after treatment in which all PGI-C ratings are stable or improved. Deucrictibant’s safety will also be evaluated.
“This study is assessing the effects of deucrictibant for people with high unmet need beyond adults with HAE type 1 and 2, such as participants with HAE with normal C1 inhibitor and adolescents between 12 and 17 years and will be evaluating the effects of deucrictibant in treating laryngeal attacks,” Lu said.
Pharvaris is testing an extended-release tablet version of deucrictibant as a prophylactic treatment to prevent swelling attacks. The company is also planning a trial of deucrictibant in people with acquired angioedema.
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