Pharvaris provides business update

Pharvaris (Nasdaq: PHVS), a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to prevent and treat hereditary angioedema (HAE) attacks, today announced the planned initiation of CHAPTER-3, the pivotal Phase 3 study of deucrictibant extended-release tablets for the prophylactic treatment of HAE; announced its intention to pursue clinical development of deucrictibant in a newly named indication, acquired angioedema due to C1-inhibitor deficiency (AAE-C1INH); and presented a robust data set highlighting the differentiating characteristics of deucrictibant.

“Given the totality of data for deucrictibant, now bolstered by new data from ongoing long-term extension studies showing tolerability and efficacy in both prophylaxis and on-demand treatment, we believe deucrictibant has the potential to become a preferred therapy for the management of HAE,” said Berndt Modig, Chief Executive Officer at Pharvaris. “We remain focused on the efficient execution of our clinical studies, with the CHAPTER-3 study expected to initiate by the end of the year while RAPIDe-3 is progressing as planned. Pharvaris has the expertise to expand deucrictibant beyond HAE to other bradykinin-mediated-disease—such as AAE-C1INH—and we are excited to explore the potential for deucrictibant to meet a currently unaddressed medical need.”

CHAPTER-3, a global, pivotal Phase 3 study of deucrictibant extended-release tablet for the prophylactic treatment of HAE attacks, is expected to initiate by year end 2024.
Startup activities are on track to initiate CHAPTER-3 by the end of 2024. CHAPTER-3 will assess the efficacy and safety of once-daily dosing of the extended-release tablet formulation of deucrictibant, which is designed to provide sustained protection from HAE attacks by maintaining plasma exposure above therapeutic level for over 24 hours and achieving pharmacokinetic steady state in approximately two to three days.

Stefan Abele, Ph.D., Chief Technical Operations Officer of Pharvaris, commented, “Pharvaris’ supply chain and CMC teams have been working diligently to ensure timely delivery of deucrictibant extended-release tablets in the commercial formulation to our Phase 3 clinical sites. The use of deucrictibant extended-release tablets in the CHAPTER-3 Phase 3 study enables us to evaluate deucrictibant’s ability to address the need for improvements in quality-of-life that people living with HAE want and deserve: a therapy providing injectable-like efficacy, from the first day of therapy, with a favorable tolerability and the convenience of once-daily oral administration.”

Pharvaris intends to pursue clinical development of deucrictibant in AAE-C1INH following publication (1) of compelling data from an investigator-initiated trial. Data in the Journal of Allergy and Clinical Immunology in July 2024 explored the potential for deucrictibant to address the unmet medical need for well-tolerated and effective therapies for the prophylactic and on-demand treatment of AAE-C1INH. A randomized, double-blind, placebo-controlled study was conducted by Investigators at the Amsterdam University Medical Center (Amsterdam UMC). Three people living
with AAE-C1INH were enrolled; the individual mean monthly attack rates were 2.0, 0.6, and 1.0 during the placebo period and 0.0 across all participants during treatment with deucrictibant. There were no severe adverse events and one self-limiting treatment-emergent adverse event (abdominal pain).

Remy S. Petersen, M.D., at Amsterdam UMC, stated, “There is an unmet need for therapies approved specifically for the treatment of AAE-C1INH. At Amsterdam UMC, we were pleased to confirm our hypothesis that a bradykinin B2 receptor antagonist, such as deucrictibant, has the potential to successfully prevent and treat AAE-C1INH. We look forward to continuing our collaboration with Pharvaris in the clinical development of deucrictibant for AAE-C1INH to further demonstrate the therapeutic benefit for those living with bradykinin-mediated angioedema.”

Differentiated clinical profile of deucrictibant presented at the Bradykinin Symposium.
A snapshot of long-term extension data from the ongoing prophylactic (CHAPTER-1 part 2: NCT05047185) and on-demand (RAPIDe-2: NCT05396105) extension studies provide evidence of the sustained product profile of deucrictibant in both HAE treatment settings.

References
(1) Petersen RS et al. J Allergy Clin Immunol. 2024 Jul;154(1):179-183