FDA lifts hold on deucrictibant as preventive treatment for HAE

Pharvaris will resume clinical testing, restart open-label extension

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) has lifted its clinical hold on deucrictibant as a prophylactic, or preventive, treatment for hereditary angioedema (HAE) attacks.

Deucrictibant developer Pharvaris said it will resume clinical testing of the therapy in HAE, including restarting the open-label extension part of the Phase 2 CHAPTER-1 clinical trial (NCT05047185).

“The lift of the clinical hold in the U.S. enables us to progress the global development of deucrictibant for long-term prophylaxis, including resuming the open-label portion of CHAPTER-1, our Phase 2 proof-of-concept study of deucrictibant for the prevention of HAE attacks, in the U.S.,” Berndt Modig, CEO of Pharvaris, said in a company press release.

Pharvaris is gearing up for Phase 3 testing of deucrictibant in HAE, both as on-demand and preventive treatment. The company plans to meet with the FDA to review key elements of the trial.

“We will request an end-of-Phase 2 meeting with the FDA to align on key elements of CHAPTER-3, the anticipated global Phase 3 study of deucrictibant extended-release tablets (PHVS719) for the prophylactic treatment of HAE attacks,” Modig said.

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HAE attacks start resolving in under 30 minutes with PHVS416 in trial

Why did the FDA lift its hold on deucrictibant?

Deucrictibant is an oral therapy that’s designed to inhibit bradykinin signaling. Bradykinin is the signaling molecule whose overactivity leads to swelling attacks in HAE. The company is developing an immediate-release formulation called PHVS416 as an on-demand treatment along with an extended-release prophylactic.

In 2022, the FDA placed a clinical hold on all clinical trials of deucrictibant following a review of preclinical data. The agency lifted its hold on testing the therapy as on-demand treatment in June, letting Pharvaris resume RAPIDe-2 (NCT05396105), a long-term extension study of deucrictibant as an on-demand HAE treatment.

The decision to lift the hold on prophylactic deucrictibant follows the completion of a six-month toxicology study in a rodent model.

“We are pleased to have worked collaboratively with the FDA to address the requests of the agency with the submission of additional nonclinical data, and we appreciate the agency’s comments and recommendations regarding study conduct,” Modig said.

The Phase 2 CHAPTER-1 study enrolled 34 adults with HAE who were given prophylactic deucrictibant or a placebo for about three months. The therapy reduced the rates of swelling attacks by more than 80% at the highest dose tested, results showed.

Those who completed the placebo-controlled part of CHAPTER-1 could continue into an open-label extension phase where all would be given prophylactic deucrictibant and monitored for long-term outcomes. The open-label extension was paused when the FDA issued its clinical hold, but is slated to resume.