Pharvaris plans filings for HAE drug after pivotal trial win

Swiss biotech Pharvaris has reported positive data from a phase 3 trial of its drug for hereditary angioedema (HAE), setting up marketing applications next year.

The drug – an extended-release formulation of bradykinin B2 receptor antagonist deucrictibant – achieved an 83% reduction compared to placebo in monthly HAE attacks, the unpredictable bouts of debilitating and painful swelling in various parts of the body that characterise the rare disease.

Shares in Nasdaq-listed Pharvaris rose more than 15% in pre-market trading after the announcement of the data from the CHAPTER-3 trial, which the company said is the first phase 3 study to demonstrate effective prophylaxis in all three types of HAE.

CHAPTER-3 enrolled 85 people with HAE type 1 (characterised by a deficiency in C1 inhibitor), HAE type 2 (dysfunctional C1 inhibitor), or HAE with normal C1 inhibitor (formerly known as type 3).

There was an 87% reduction in monthly attacks in the 80 subjects with HAE type 1 and type 2, and the drug also found its mark in all secondary endpoints, including reductions in attack rate from baseline and the percentage of attack-free participants.

Pharvaris is also developing another oral formulation of deucrictibant for on-demand treatment of HAE attacks, which was shown to be effective in the RAPIDe-3 study reported last December and was filed with the US FDA in June. A decision on that marketing application is due next April.

HAE is becoming quite a crowded indication for both prophylaxis and on-demand treatment, but there is still a demand for treatments that can offer "improved disease control and health-related quality of life, with reduced treatment burden," according to CHAPTER-3 principal investigator Marc Riedl.

Riedl, who is clinical director of the US Hereditary Angioedema Association (HAEA) Angioedema Centre at the University of California San Diego (UCSD), said the efficacy, tolerability, and oral administration of Pharvaris' drug position it as "a potentially important addition to HAE clinical practice, supporting individualised treatment strategies."

At present, the only FDA-approved oral therapies for HAE are BioCryst's Orladeyo (berotralstat) and KalVista Pharma's Ekterly (sebetralstat), both plasma kallikrein inhibitors, which have been cleared for prophylaxis and on-demand treatment, respectively.

Analysts have suggested that deucrictibant could eventually generate peak sales of $1 billion to $2 billion if both formulations are approved.

"People living with HAE have been waiting for a well-tolerated oral therapy with injectable-like efficacy; we believe deucrictibant XR can help address this unmet need," said Pharvaris president Peng Lu.

The company is also running CHAPTER-4, an open-label long-term extension study of deucrictibant XR for the prophylaxis of HAE, as well as CREAATE, a phase 3 study looking at the drug's potential in preventing attacks in acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH), another HAE-like condition.