(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), today announced that results from a Pharvaris-sponsored non-interventional, mixed methods, real-world study assessing the patient experience during acute HAE attacks across alternative endpoints used in clinical studies have been published in Clinical Reviews in Allergy & Immunology. The study evaluated the patient experience with HAE attack manifestations, and what constitutes meaningful changes in those manifestations, to support the inclusion of meaningful endpoints in clinical studies for on-demand treatment (ODT) of HAE attacks, such as RAPIDe-3 (NCT06343779).

“This study and its findings explore important insights into the care of those living with HAE; by validating patient-reported outcome measures with rigorous evidence, we have supported the definition of clinical study endpoints and reinforced trust in the results of those studies, resulting in HAE treatment decisions ultimately being guided by patient experience,” said Danny M. Cohn, M.D., Ph.D., Department of Vascular Medicine, Amsterdam UMC (an accredited center of ACARE) and an investigator for the study. “The ability to truly understand the impact of meaningful symptom changes will not only support the development of novel treatments but provide additional evidence to clinicians and people living with HAE to inform decisions on the most appropriate treatment options for them.”

Although approved medicines exist for the on-demand treatment of HAE attacks, there have been no head-to-head studies of on-demand therapies, and cross-trial comparisons have been challenging due to lack of uniformity in study design. Additionally, (1) generation of evidence related to the key symptoms experienced by people during HAE attacks, (2) insights into the subsequent perception from patients as to what are clinically-meaningful changes in symptoms, (3) validation of the content of various patient-reported outcome (PRO) instruments to support the evaluation of those symptoms, and (4) confirmation of patient understanding and interpretation of that content, all could help in the evaluation of on-demand therapies by regulators, payers, and the HAE community.

This non-interventional study included participants with HAE in the U.S. who treated their HAE attacks with standard of care in accordance with their experience in real-world clinical practice. The study used a mixed methods approach and had a quantitative phase (real-time electronic PRO assessments during HAE attacks) and a qualitative phase (post-attack interview). The study aimed to evaluate PRO instruments—specifically the Patient Global Impression of Change (PGI-C), Patient Global Impression of Severity (PGI-S), and Angioedema syMptom Rating scAle (AMRA-3 and AMRA-5)—in capturing the patient experience during HAE attacks and to define meaningful change thresholds to inform the design of clinical trials for ODT of acute attacks.

Study Results
This mixed methods study provides strong evidence that the PGI and AMRA instruments are reliable, valid, and sensitive tools for assessing PROs in HAE attacks. Within the PRO assessments, most concepts (i.e., skin swelling, abdominal pain, difficulty swallowing, and voice change) were considered important by participants. Qualitative interviews confirmed that even relatively small improvements could be meaningful, such as the moment an attack was no longer worsening, as captured by the endpoint of End of Progression.

Consistency across all PRO assessments of attack manifestation and response assessment were seen; End of Progression was the first-in-time achieved endpoint, followed by symptom relief, then symptom resolution. Importantly, the median time to onset of initial symptom relief as measured as PGI-C rating of at least “a little better” aligned more closely with the timing of AMRA-3 ≥20% than with the timing of AMRA-3 ≥30%. These results informed the hierarchy of endpoints in the Phase 3 RAPIDe-3 trial of deucrictibant and may also inform future trials of ODTs for HAE attacks.

“By validating patient-reported outcome measures in a real-world setting, we are ensuring that the experience and voices of people living with HAE directly inform how we assess new therapies in development” said Peng Lu, M.D., Ph.D., Chief Medical Officer of Pharvaris. “The findings support the use of PGI and AMRA instruments to evaluate endpoints in clinical trials for on-demand HAE treatments, including within our RAPIDe-3 study—the first-ever on-demand HAE study to be designed with prespecified endpoints being fully compliant with the Core Outcome Set recommended in the AURORA Consensus1. This study gives us greater confidence that clinical outcomes truly reflect meaningful benefits for patients. These results not only strengthen our clinical programs but also reinforce our commitment to advancing patient-centered care and providing oral alternatives that improve upon standard of care to people with by HAE.”

To the full publication

References
1 Petersen RS, et al. J Allergy Clin Immunol Pract. 2024 Jun;12(6):1614-1621. doi:10.1016/j.jaip.2024.04.007.