Pharvaris is advancing the clinical development of deucrictibant, an oral bradykinin B2 receptor antagonist, for both hereditary angioedema (HAE) and acquired angioedema (AAE). The company outlined its strategic priorities for 2025, emphasizing the ongoing Phase 3 trials and expansion into AAE treatment. With a strong financial position, Pharvaris aims to address unmet needs in bradykinin-mediated angioedema.
Phase 3 Trials Progressing for HAE
The global pivotal Phase 3 study, RAPIDe-3 (NCT06343779), evaluating deucrictibant immediate-release capsule (20 mg) for the on-demand treatment of HAE attacks, is progressing as planned. The trial targets approximately 120 participants, with topline data anticipated in the first quarter of 2026. The primary efficacy endpoint is the time to onset of symptom relief, measured by the Patient Global Impression of Change (PGI-C) rating.
CHAPTER-3 (NCT06669754), a randomized, double-blind, placebo-controlled Phase 3 study of orally administered deucrictibant extended-release tablet for the prophylactic treatment of HAE attacks, was initiated in 2024. The study aims to enroll approximately 81 adult and adolescent participants, with topline data expected in the second half of 2026. The primary endpoint is the time-normalized number of investigator-confirmed HAE attacks during the 24-week treatment period.
Berndt Modig, Chief Executive Officer of Pharvaris, stated, "This year is paramount to Pharvaris as we continue clinical development of deucrictibant to help address unmet needs for those living with bradykinin-mediated angioedema."
Expanding into Acquired Angioedema (AAE)
Pharvaris is also planning clinical development of deucrictibant for the treatment of acquired angioedema due to C1-INH deficiency (AAE-C1INH). Currently, there are no approved therapies for this condition. The company has engaged with the FDA for feedback on a clinical development plan and intends to initiate a clinical study in 2025, pending regulatory feedback.
Data from an investigator-initiated trial published in the Journal of Allergy and Clinical Immunology in July 2024, explored deucrictibant's potential in AAE-C1INH. The study, conducted at Amsterdam University Medical Center, showed promising results with deucrictibant. Three patients with AAE-C1INH experienced a reduction in mean monthly attack rates from 2.0, 0.6, and 1.0 during the placebo period to 0.0 during treatment with deucrictibant. There were no severe adverse events reported.
Long-Term Data and Unmet Needs
Long-term extension data from the CHAPTER-1 open-label extension (OLE) study showed that participants experienced a 93% reduction in HAE attacks compared to baseline with deucrictibant prophylaxis. Data from the RAPIDe-2 OLE study showed a median onset of symptom relief in approximately 1.1 hours, with 85.8% of attacks resolving completely within 24 hours with deucrictibant immediate-release capsule.
Presentations at recent medical congresses highlighted the unmet need for novel oral options in HAE treatment. Data from the Adelphi Disease Specific Programme indicated that approximately one-third of HAE airway attacks were not treated, underscoring the need for portable therapies. A poster presented at the BSI-CIPN Conference characterized the experience of people living with HAE in the United Kingdom, noting that the most common unmet need was a desire for a different route of administration, highlighting the potential of oral deucrictibant.
Financial Position
As of September 30, 2024, Pharvaris reported cash and cash equivalents of €305 million, providing a strong financial runway into the third quarter of 2026. This financial stability supports the company's ongoing clinical trials and expansion efforts.
With ongoing Phase 3 trials and plans to expand into AAE, Pharvaris is poised to make significant strides in addressing the unmet needs of patients with bradykinin-mediated angioedema.
