RARE Daily

FDA Lifts Clinical Hold of Pharvaris’ Deucrictibant for the Prophylactic Treatment of HAE Attacks

January 25, 2024

Rare Daily Staff

The U.S. Food and Drug Administration) has lifted the clinical hold on the Investigational New Drug application for Pharvaris’ deucrictibant for the prophylactic treatment of Hereditary angioedema attacks following review of data from a 26-week rodent toxicology study.

“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.,” said Berndt Modig, CEO of Pharvaris.

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.

Current therapies are limited by invasive routes of drug administration (injection or infusion), inconvenient dosing regimens, or undesired side effects. Surveys of patients with HAE overwhelmingly show that they seek additional treatment options.

Pharvaris has a platform of novel, potent, and selective B2-receptor antagonist small molecules for the treatment of B2-receptor-mediated diseases. 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.

In August 2022, the FDA placed clinical studies of deucrictibant, including CHAPTER-1, on hold. Pharvaris notified ex-U.S. country-specific regulatory authorities of the clinical hold in the United States. The regulatory status of deucrictibant outside the United States was not affected.

In June 2023, FDA removed a separate clinical hold of deucrictibant for the on-demand treatment of HAE in the United States following FDA review of data from a preplanned interim analysis of a 26-week rodent toxicology study. In December 2023, Pharvaris announced positive top-line clinical data from the phase 2 CHAPTER-1 study of deucrictibant for the prophylactic treatment of HAE attacks.

Modig said the company 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 for the prophylactic treatment of HAE attacks.

Photo: Berndt Modig, CEO of Pharvaris

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