Pharvaris' oral hereditary angioedema med slashes attacks in comeback from FDA hold

Patients taking Pharvaris’ preventative oral medicine for hereditary angioedema (HAE) experienced an 84.5% reduction in monthly attacks during a phase 2 study. The results represent a comeback for the medicine, which was placed on a clinical hold by the FDA last year.

Pharvaris said Wednesday that an immediate-release capsule version of deucrictibant achieved the primary endpoint of the midstage CHAPTER-1 trial, which was testing whether the oral therapy could serve as a long-term prophylaxis against angioedema attacks for patients with type 1 and 2 of the condition. The 34 patients were randomized to receive one of two doses—or placebo—for 12 weeks.

The primary endpoint was the number of confirmed HAE attacks during the treatment period. Deucrictibant achieved an 84.5% reduction on this measure when compared to placebo with the 40-mg daily dose.

The therapy also reduced the severity of attacks and decreased the number of attacks that had to be treated with on-demand medication, which were the trial's secondary endpoints.

Pharvaris said that the med was well tolerated through the 12 weeks of the study and that there were no serious adverse events or severe treatment-emergent adverse events and no adverse events that led to discontinuation.

Chief Medical Officer Peng Lu, M.D., Ph.D., touted the results as proof that deucrictibant can reduce the treatment burden for patients with HAE. The condition is characterized by recurrent episodes of severe swelling of the limbs, face, intestinal tract and airway.

“The HAE community is seeking highly effective, well-tolerated and less burdensome therapies. The CHAPTER-1 data represent an important step forward in the evolution of HAE treatment,” said Marc A. Riedl, M.D., who served as principal investigator on the trial. He is also a professor of medicine at the Angioedema Center at the University of California, San Diego.

Pharvaris did not lay out the specific next steps for deucrictibant, an oral bradykinin B2 receptor antagonist, besides noting that the results will be submitted to the FDA.

The clinical win comes just under six months after the FDA lifted its hold on the use of deucrictibant as an on-demand treatment in the U.S. Pharvaris had to complete a 26-week rodent toxicology study to get the trial back on track in the U.S. but continued with the research elsewhere. The prophylaxis remains on clinical hold however Pharvaris was able to initiate the study globally. 

Two oral versions of deucrictibant—a capsule for rapid onset to treat acute attacks and an extended-release pill for prophylaxis—are being developed with the goal of reducing the treatment burden for patients with HAE. The extended-release pill is being tested in a phase 1 program.

Editor's note: This story was updated at 1:52 p.m. ET on Dec. 6, 2023, to clarify that the prophylaxis program remains on clinical hold.