Pharvaris Reports Positive Top-line Phase 2 Study Data of Deucrictibant for Treatment of HAE Attacks

Rare Daily Staff

Swiss biopharma Pharvaris reported positive top-line data from the CHAPTER-1 phase 2 clinical study meeting its primary endpoint, with deucrictibant demonstrating statistically significant and clinically meaningful results as an oral preventative treatment for people living with hereditary angioedema.

Hereditary angioedema (HAE) is a rare genetic disorder that results in recurring attacks of edema, or swelling, in various parts of the body, including the abdomen, face, feet, genitals, hands and throat. The swelling can be debilitating and painful. Attacks that obstruct the airways can cause asphyxiation and are potentially life threatening.

HAE attacks may occur very early in childhood. Potentially fatal upper airway angioedema has been reported in patients as young as 3 years old. HAE diagnosis can take an average of 8.4 years after symptom onset. HAE affects an estimated 1 in 50,000 people worldwide and is often underrecognized, under diagnosed, and under treated. There are currently no long-term prophylactic treatments approved for HAE patients younger than 6 years.

Deucrictibant is a potent, selective, and orally available antagonist of the bradykinin B2 receptor. By inhibiting bradykinin signaling through the bradykinin B2 receptor, deucrictibant has the potential to treat the clinical signs of an HAE attack and to prevent the occurrence of attacks. Based on its chemical properties, Pharvaris is developing two formulations of deucrictibant for oral administration; a capsule to enable rapid onset of activity for acute treatment, and an extended-release tablet to enable sustained absorption and efficacy in prophylactic treatment.

CHAPTER-1 is a double-blind, placebo-controlled phase 2 study evaluating the efficacy as well as the safety and tolerability of deucrictibant for long-term prophylaxis against angioedema attacks in HAE-1/2. In the study, 34 participants were enrolled globally and randomized to receive one of two doses of deucrictibant (20 mg/day or 40 mg/day) or placebo for 12 weeks of treatment. Deucrictibant immediate-release capsule (PHVS416) was dosed twice-a-day as a proof-of-concept for the once-daily deucrictibant extended-release tablet (PHVS719), which is the intended formulation for the prophylactic treatment of HAE. The open-label portion of the CHAPTER-1 study is ongoing at the 40 mg/day dose.

The study’s primary endpoint measured the time-normalized number of investigator-confirmed HAE attacks during the treatment period. The monthly attack rate was reduced by 84.5 percent compared to placebo in participants who received 40 mg/day of deucrictibant.

“Deucrictibant is the first HAE treatment with the potential to combine injectable-like efficacy and a favorable safety profile with the convenience of an oral therapy,” said Peng Lu, chief medical officer of Pharvaris. “The study demonstrates, for the first time ever, that antagonism of the bradykinin B2 receptor can provide early and sustained protection from HAE attacks, including substantial reduction of moderate and severe attacks, with clinically meaningful improvement in health-related quality of life.”

In the analysis of the secondary endpoints, deucrictibant demonstrated clinically meaningful improvement in the severity of attacks and a decrease in the number of attacks treated with on-demand medication. Participants on deucrictibant treatment experienced a meaningful improvement in their quality of life with 92.3 percent reduction in occurrence of moderate and severe attacks and 92.6 percent fewer attacks treated with on-demand medication by participants.

Throughout 12 weeks of treatment in CHAPTER-1, both doses of deucrictibant were well-tolerated. There were no serious adverse events, no severe treatment-emergent adverse events, and no adverse events leading to treatment discontinuation.

In August 2022, the U.S. Food and Drug Administration placed clinical studies of deucrictibant, including CHAPTER-1, on hold. Pharvaris notified country-specific regulatory authorities in Canada, Europe, Israel, and the United Kingdom regarding the clinical holds in the United States, and the regulatory status of deucrictibant outside the United States has not been affected.

In June 2023, Pharvaris announced the removal of the clinical hold of deucrictibant for the on-demand treatment of HAE in the U.S. Pharvaris has completed the 26-week rodent toxicology study requested by the FDA, which it believes meet FDA’s objective. Pharvaris is preparing to submit the study results to the FDA by the end of the year.

“These study results, together with the compelling data from our on-demand program, further strengthens our confidence that deucrictibant can become the preferred option to treat as well as prevent HAE attacks,” said Berndt Modig, CEO of Pharvaris.