Pharvaris reports long-term deucrictibant data showing sustained HAE attack reduction over nearly 34 months, improved quality of life and durable on-demand treatment responses.
Written By: Sravani Pamanji, PharmD
Reviewed By: Pharmacally Editorial Team
Pharvaris announced additional clinical data for its investigational oral bradykinin B2 receptor antagonist deucrictibant on November 12, 2026, ahead of presentations at the American College of Allergy, Asthma and Immunology (ACAAI) 2026 Annual Scientific Meeting. The findings extend the company’s clinical evidence beyond the previously reported Phase 3 CHAPTER-3 results, highlighting longer-term prophylactic efficacy, patient-reported outcomes and the durability of responses following on-demand treatment.
The new data cover the Phase 2 CHAPTER-1 open-label extension (OLE), Phase 3 RAPIDe-3 study and analyses evaluating the potential combined use of deucrictibant’s extended-release (XR) and immediate-release (IR) formulations.
Long-Term Prophylaxis: Attack Reduction Sustained for Nearly 34 Months
Final results from the Phase 2 CHAPTER-1 open-label extension (NCT05047185) showed that reductions in HAE attack rates were maintained during long-term deucrictibant treatment.
Participants experienced an average 92.4% reduction in attack rate from the baseline of the original randomised controlled study. The overall mean monthly attack rate declined from 2.18 attacks at baseline to 0.12 during the extension period. Maximum exposure across the CHAPTER-1 programme reached 33.8 months, with a mean treatment duration of 22.2 months in the extension phase.
At follow-up assessments through week 132, the majority of participants achieved at least a 90% reduction in attack rate.
Long-term treatment was generally well tolerated, with no treatment-related serious adverse events or treatment-emergent adverse events leading to study discontinuation, withdrawal or death.
Additional patient-reported outcomes from CHAPTER-1 showed sustained improvements in health-related quality of life. Among participants reaching at least week 86 of the extension, all reported feeling much better compared with their study baseline. Mean Angioedema Quality of Life (AE-QoL) total scores improved by 26.9 points, with the greatest improvements in functioning and fear/shame domains.
These findings extend the prophylactic evidence beyond the 24-week Phase 3 CHAPTER-3 study, in which once-daily deucrictibant XR 40 mg reduced the mean monthly HAE attack rate by 83% compared with placebo. CHAPTER-3 also met its primary and all secondary efficacy endpoints.
On-Demand Treatment: RAPIDe-3 Shows Sustained Clinical Responses
Separate analyses from the Phase 3 RAPIDe-3 programme (NCT05047182) provide additional evidence for deucrictibant IR 20 mg as an on-demand treatment for acute HAE attacks.
Among 88 participants with paired treated attacks, the median time to End of Progression (EoP) was 17.47 minutes with deucrictibant, compared with 228.67 minutes with placebo. EoP represents the earliest evidence that attack manifestations have stopped worsening and are beginning to progress towards relief and resolution.
Importantly, the additional analysis examined whether treatment responses were maintained after predefined clinical endpoints were achieved. More than 95% of attacks reaching the specified relief and resolution endpoints maintained those responses throughout the respective assessment periods. More than 80% of attacks achieving these endpoints with sustained responses did so following a single capsule.
These findings add a response-durability dimension to the previously reported rapid onset of action with deucrictibant IR.
Potential Combination of Preventive and On-Demand Formulations
Pharvaris also reported pharmacokinetic modelling and nonclinical analyses evaluating the potential combined use of deucrictibant XR 40 mg for prophylaxis and IR capsules for breakthrough attacks during preventive treatment.
The modelling indicated that systemic exposure following XR administration combined with one or two IR capsules remained below the nonclinical no-observed-adverse-effect level and the highest exposure previously evaluated in humans.
This provides supportive evidence for the potential use of both formulations within a combined treatment strategy. However, these findings are based on pharmacokinetic modelling and nonclinical safety assessments, rather than a clinical trial demonstrating the efficacy of combined treatment.
Cardiovascular Safety and Development Outlook
An integrated cardiovascular safety assessment covering 25 Pharvaris-sponsored studies and more than 740 unique participants exposed to deucrictibant as of June 10, 2026, found no evidence of QTc prolongation or increased cardiovascular event risk. The assessment included both prophylactic and on-demand treatment programmes.
The broader dataset supports continued clinical development, although longer-term exposure and post-marketing evidence, if approved, will remain important for defining the drug’s safety profile.
Clinical Interpretation
The November 12 data add important dimensions to deucrictibant’s development. The CHAPTER-1 extension supports sustained attack reduction and improvements in quality of life during longer-term prophylaxis, while RAPIDe-3 provides evidence of maintained responses following on-demand treatment.
Together, these findings strengthen the rationale for developing XR and IR formulations to address different stages of HAE management. The potential combination of both formulations could offer an additional treatment strategy, although its clinical benefit remains to be established.
The evidence also requires appropriate qualification. CHAPTER-1 was an open-label extension without a concurrent placebo comparator, while the XR/IR combination findings rely on modelling rather than clinical efficacy data. Nevertheless, the additional findings provide a broader clinical picture of deucrictibant as Pharvaris advances its regulatory development programme.
References
Pharvaris Presents Clinical and Real-World Data at the ACAAI 2026 Annual Scientific Meeting, Pharvaris, 12 November 2026
Study of Oral Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults with HAE (CHAPTER-3), ClinicalTrials.gov ID NCT06669754
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
Review Supports Bradykinin B2 Receptor as a Validated Target in Bradykinin-Mediated Angioedema, Pharmacally, 23 July 2026
About the Writer
Sravani Pamanji is a PharmD (LinkedIn) professional with experience in scientific writing, medical literature review, drug profile preparation, and clinical case documentation. She has contributed to scientific publication and presented at the 74th Indian Pharmaceutical Congress. Her training includes ICH GCP E6(R3), scientific research, and medication safety. She is passionate about evidence-based medical communication and accurate dissemination of clinical and pharmaceutical information.