Pharvaris: Long-term clinical data for prevention and treatment of hereditary angioedema attacks

Pharvaris (Nasdaq: PHVS), a late-stage biopharmaceutical company developing novel, oral bradykinin B2 receptor antagonists to help address unmet needs of those living with bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH), highlighted safety and efficacy data of deucrictibant, which is currently being evaluated in two pivotal Phase 3 studies, following long-term dosing in the prophylactic and on-demand settings at the American Academy of Allergy, Asthma, & Immunology’s Annual Scientific Meeting (AAAAI) and World Allergy Organization (WAO) Joint Congress, which was held from February 28–March 3, 2025, in San Diego, CA.

“Topline results of deucrictibant in both prophylactic and on-demand randomized clinical trials substantiate our belief in the mechanism and molecule to provide choice to those living with HAE; continued analyses of clinical outcomes and health-related quality of life measures from the extension studies, such as these presented at the 2025 AAAAI/WAO Joint Congress, help solidify our confidence in deucrictibant’s ability to meet existing unmet needs in the HAE community,” said Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris. “The safety and efficacy data of deucrictibant following long-term dosing in a prophylactic clinical setting is especially noteworthy. Participants experienced a median of zero days with attack symptoms each month, and enhanced quality-of-life, specifically within the observed HRQoL domains of the greatest improvement—‘functioning’ and ‘fear and shame’—which are particularly relevant to people living with HAE.”

Dr. Lu continued, “Additionally, we understand from the HAE community that there is a desire for an oral, on-demand therapy that can rapidly and completely treat any type of attack with a single dose. Although the sample size is small, in line with the rarity of these types of attacks, we are pleased to share data from seven upper airway, including laryngeal, attacks that were treated with deucrictibant; these safety and efficacy findings were consistent with those seen in the 328 non-upper airway attacks treated with deucrictibant showing rapid and complete symptom resolution with a single dose. The encouraging data from these extension studies further underscore our opportunity to potentially introduce a therapeutically meaningful oral therapy for the prevention and treatment of HAE attacks, the profile of which we aim to confirm with Phase 3 data.”

Prophylactic Program: CHAPTER-1 Open-Label Extension (OLE)
An analysis of the ongoing OLE (Part 2) of the Phase 2 study of orally administered deucrictibant for the prophylactic treatment of HAE, CHAPTER-1 (NCT05047185), explores safety and effectiveness findings from 30 participants who received deucrictibant 40 mg/day for a mean treatment duration of 12.8 months (data snapshot from June 10, 2024). The maximum exposure to deucrictibant based on available study data at the time of data cutoff was 20.8 months in the OLE, and 23.7 months in the entire study. Deucrictibant was well-tolerated with no safety signals.

Ongoing treatment with deucrictibant resulted in sustained protection from HAE attacks, including total monthly attack rate, “moderate and severe” attack rate, and rate of attacks treated with on-demand medication remaining low during OLE. In a poster presentation, Marc A. Riedl, M.D., M.S. also shared that at the time of data cut-off the median proportion of days with symptoms in deucrictibant-treated participants in the OLE was zero each month after a mean treatment duration of 12.8 months.

When evaluating health-related quality of life (HRQoL), participants were asked to report their outcomes through two measures: Patient Global Assessment of Change (PGA-Change) and the Angioedema Quality of Life Questionnaire (AE-QoL). The data shared in a poster presentation by John Anderson, M.D showed that PGA-Change, HRQoL was improved at week 12 and as well as at week 62 compared to study baseline in participants treated with deucrictibant. AEQoL measurements showed a clinically meaningful improvement at week 4 compared to baseline, which was then maintained throughout treatment, with “functioning” and “fear/shame” being the domains with greatest changes.

On-Demand Program: RAPIDe-2 Extension Study
RAPIDe-2 (NCT05396105) is an ongoing two-part Phase 2/3 extension study, evaluating long-term safety and efficacy of orally administered deucrictibant immediate-release capsule for the on-demand treatment of HAE attacks. The analysis (cutoff date: June 10, 2024) was presented by Michael E. Manning, M.D., in a poster presentation and showed that deucrictibant was generally well-tolerated with no safety signals observed. The data set includes a total of 337 attacks, seven of which met the definition of an upper airway, including laryngeal, attack. Of these upper airway attacks, the time to onset of symptom relief, as measured by the Patient Global Impression of Change (PGI-C), was 0.9 hours (N=7) and was consistent with that of non-airway attacks (1.1 hours, N=328). The majority of upper airway attacks were treated with a single dose of deucrictibant (85.7%), which was similar to that of non-airway attacks treated with a with a single dose of deucrictibant (85.4%).

About Deucrictibant
Deucrictibant is a novel, potent, oral small-molecule bradykinin B2 receptor antagonist currently in clinical development. By inhibiting bradykinin signaling through the bradykinin B2 receptor, deucrictibant is being investigated for its potential to prevent the occurrence of HAE attacks and to treat the manifestations of attacks if/when they occur. Based on its chemical properties, Pharvaris is developing two formulations of deucrictibant for oral administration: an extended-release tablet to enable sustained absorption and efficacy in prophylactic treatment, and an immediate-release capsule to enable rapid onset of activity for on-demand treatment.