Pharvaris announces Phase 3 RAPIDe-3 results for oral deucrictibant, showing faster symptom relief in hereditary angioedema compared with placebo.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Pharvaris has announced the publication of results from its Phase 3 RAPIDe-3 trial of oral deucrictibant immediate-release (IR) capsules for the on-demand treatment of hereditary angioedema (HAE) attacks in The Lancet. Published on October 8, 2026, the findings provide pivotal clinical evidence supporting the company’s development of deucrictibant, an oral bradykinin B2 receptor antagonist, for acute HAE attacks.
The global, randomised, double-blind, placebo-controlled crossover trial met its primary endpoint and all 11 secondary efficacy endpoints. Median time to onset of symptom relief was 1.28 hours with deucrictibant, compared with more than 12 hours with placebo (p<0.0001). Median time to complete symptom resolution was 11.95 hours with deucrictibant.
Pharvaris said the results support the potential of oral bradykinin B2 receptor antagonism as an on-demand treatment approach for HAE. The company’s New Drug Application (NDA) for deucrictibant IR is under review by the U.S. Food and Drug Administration (FDA), while its Marketing Authorisation Application (MAA) is under review by the European Medicines Agency (EMA).
RAPIDe-3 Evaluates Pharvaris’s Oral Deucrictibant Across a Global Population
RAPIDe-3 (NCT06343779) was conducted at 59 sites across 24 countries on six continents. The Phase 3 study evaluated a 20 mg oral immediate-release deucrictibant capsule in adolescents aged 12 to under 18 years and adults aged 18–75 years experiencing HAE attacks.
A total of 134 participants were randomised, including 10 adolescents and 124 adults. Participants followed one of two treatment sequences, receiving deucrictibant for one qualifying attack and placebo for another, or the reverse sequence. In total, 113 participants treated 201 attacks, while the primary efficacy analysis included 88 participants with paired attacks, representing 176 attacks.
The primary endpoint was time to onset of symptom relief, defined as achieving a Patient Global Impression of Change (PGI-C) rating of at least “a little better” at two consecutive timepoints within 12 hours after treatment.
The study also incorporated prespecified endpoints designed to align with the core outcomes recommended by the international AURORA Delphi Consensus for on-demand HAE clinical trials.
Pharvaris Reports Faster Symptom Relief and Attack Resolution
According to the published results, median time to symptom relief was 1.28 hours with deucrictibant (95% confidence interval [CI] 1.05–1.52), compared with more than 12 hours with placebo (95% CI 5.82 to greater than 12; p<0.0001).
At four hours after treatment, symptom relief was reported in 69 of 83 evaluable deucrictibant-treated attacks (83%), compared with 24 of 87 placebo-treated attacks (28%; p<0.0001).
The treatment also improved secondary efficacy outcomes. Median time to substantial symptom relief was 2.85 hours with deucrictibant versus more than 12 hours with placebo. Median time to reduction in attack severity was 2.41 hours versus more than 12 hours, respectively. Both comparisons were statistically significant (p<0.0001).
Deucrictibant shortened the median time to End of Progression (EoP), the point at which attack symptoms stop worsening, to 17.47 minutes compared with 228.67 minutes with placebo (p<0.0001).
Median time to complete symptom resolution was 11.95 hours with deucrictibant. Within 24 hours, complete symptom resolution occurred in 50 of 83 evaluable deucrictibant-treated attacks (60%), compared with 13 of 88 placebo-treated attacks (15%).
Rescue-medication use was also lower with deucrictibant. Conventional on-demand rescue therapy was used within 24 hours in 8 of 88 deucrictibant-treated attacks (9%), compared with 39 of 88 placebo-treated attacks (44%; p<0.0001).
Pharvaris reported that efficacy outcomes were consistent across subgroups defined by age, geographic location, HAE type, use of long-term prophylaxis, attack severity and attack location. These included participants with HAE associated with normal C1 inhibitor levels and those experiencing non-severe laryngeal attacks.
Pharvaris Reports a Generally Well-Tolerated Safety Profile
Pharvaris reported that deucrictibant was generally well tolerated in RAPIDe-3, with no new safety signals observed.
Fatigue was the only adverse event reported more than once within three days after treatment, occurring in two participants; one event was considered unrelated to treatment. No treatment-related adverse events were assessed as severe or serious, and no adverse events led to treatment discontinuation.
These findings describe the safety profile observed in RAPIDe-3. Further clinical experience and longer-term follow-up will be important to characterise the treatment’s safety more fully.
Results Build on Pharvaris’s Deucrictibant Development Programme
The RAPIDe-3 findings build on results from Pharvaris’s Phase 2 RAPIDe-1 study, published in The Lancet Haematology in April 2026. Pharvaris is also conducting RAPIDe-2 (NCT05396105), an open-label extension study evaluating immediate-release deucrictibant for on-demand treatment of HAE attacks. Separately, in the Phase 3 CHAPTER-3 trial, Pharvaris reported that extended-release deucrictibant reduced the mean monthly HAE attack rate by 83% versus placebo, supporting its development for long-term attack prevention.
In its October 8 announcement, Pharvaris highlighted the consistency of the RAPIDe-3 findings across patient subgroups. Peng Lu, M.D., Ph.D., president of Pharvaris, said the results underscore the clinical relevance of targeting the bradykinin B2 receptor, which acts downstream of the pathways that generate excess bradykinin.
Marc A. Riedl, M.D., M.S., the principal RAPIDe-3 investigator and lead author of the publication, also highlighted the potential relevance of an orally administered bradykinin B2 receptor antagonist for on-demand treatment. Pharvaris stated that publication in The Lancet would make the findings accessible to clinicians, researchers and patients internationally.
FDA and EMA Review Deucrictibant for On-Demand HAE Treatment
Pharvaris’s NDA for deucrictibant IR for on-demand treatment of HAE attacks is under review by the FDA, with a Prescription Drug User Fee Act (PDUFA) target action date of April 23, 2027. The company’s MAA is also under review by the EMA.
Deucrictibant remains investigational for this indication pending regulatory decisions. If approved, Pharvaris states that it would be the first approved oral bradykinin B2 receptor antagonist for on-demand treatment of HAE attacks.
The RAPIDe-3 results provide evidence of faster symptom relief and resolution compared with placebo. However, the trial did not establish superiority over other active on-demand treatments. The ongoing regulatory reviews will determine whether deucrictibant becomes an approved oral treatment option for people living with HAE.
Reference
Riedl M, Li P, Adatia A et al., Oral deucrictibant for on-demand treatment of hereditary angioedema attacks: a phase 3, multicentre, randomised, double-blind, placebo-controlled crossover trial, The Lancet, October 08, 2026, https://doi.org/10.1016/S0140-6736(26)01296-1
Phase 3 Study Results Highlighting Deucrictibant’s Rapid and Sustained Efficacy in Treating HAE Attacks Published in The Lancet, Pharvaris, 08 October 2026
Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adolescents and Adults with Hereditary Angioedema (RAPIDe-3), ClinicalTrials.gov ID NCT06343779
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.