Pharvaris highlights their drugs potential to prevent and treat bradykinin-mediated angioedema attacks

“Pharvaris embraced the opportunity to engage in scientific exchange with the HAE thought leader community during EAACI as we presented data supporting the differentiated profile of deucrictibant for the prophylactic and on-demand treatment of bradykinin-mediated angioedema attacks,” said Berndt Modig, Chief Executive Officer of Pharvaris. “Building on our R&D call from last week, we shared data demonstrating the potential for deucrictibant to address the unmet needs of people living with bradykinin-mediated angioedema beyond HAE-1/2. Deucrictibant showed sustained attack reduction and improved quality of life measures in the randomized portion of the CHAPTER-1 study, which was maintained in the open-label extension study, as well as early-onset symptom relief and complete symptom resolution in a single dose in most attacks in our ongoing RAPIDe-2 on-demand long-term extension study. Finally, RAPIDe-3 is the first and only phase 3 on-demand study that will explore ‘end-of-progression’ as a new pre-specified endpoint, which is particularly meaningful for people living with HAE. Together with the outcomes from other study endpoints, we will be able to assess the full impact of deucrictibant on an HAE attack from start to end.”

Details of the presentations are outlined below:

Prophylaxis

Long-Term Safety and Efficacy of Oral Deucrictibant for Prophylaxis in Hereditary Angioedema: Results of the CHAPTER-1 Open-Label Extension Study, a poster presentation by Emel Aygören-Pürsün, M.D.

• First-ever bradykinin B2 receptor antagonism mechanism-on-mechanism prophylactic/on-demand data supports potential for deucrictibant portfolio.
• The ongoing Phase 2 CHAPTER-1 open-label extension (OLE) study provides further evidence on the long-term safety and efficacy of oral deucrictibant for prevention of HAE attacks.
• The attack rate has remained low, irrespective of baseline attack rate, for over a year and a half in OLE participants.
• When evaluating mechanism-on-mechanism responses, the response to icatibant for on-demand treatment of breakthrough attacks appeared to be maintained when used for breakthrough attacks during prophylactic treatment with deucrictibant.

Long-Term Prophylactic Treatment with Oral Deucrictibant Improves Disease Control and Health-Related Quality of Life in Participants with Hereditary Angioedema in the CHAPTER-1 Open-Label Extension Study, a flash talk by Markus Magerl, M.D.

• The impact of deucrictibant treatment on health-related quality of life (HRQoL), disease control, and treatment satisfaction during the ongoing CHAPTER-1 OLE was evaluated.
• All of the participants who received deucrictibant reported clinically meaningful improvements in HRQoL at the end of the randomized portion of the trial, which was maintained up to the latest timepoint assessed at the time of data cutoff (week 62) of the OLE.
• All of the participants in the OLE reported well controlled HAE and a high level of satisfaction with treatment.

CHAPTER-3 Phase 3 Trial Design: Efficacy and Safety of the Oral Bradykinin B2 Receptor Antagonist Deucrictibant Extended-Release Tablet for Prophylaxis of Hereditary Angioedema Attacks, a flash talk by William Lumry, M.D.

• CHAPTER-3 is an ongoing, global, Phase 3 study designed to evaluate the efficacy and safety of once-daily, oral deucrictibant (40 mg/day) extended release (XR) tablet for prophylaxis of attacks in adolescents and adults with HAE.
• Results from the Phase 2 CHAPTER-1 study support the CHAPTER-3 study design.

Health-Related Quality of Life and Clinical Characteristics in People Living with Hereditary Angioedema Prescribed Long Term Prophylaxis Alone and On-Demand Treatment Alone, an oral presentation by Laurence Bouillet, M.D., Ph.D.

• A real-world cross-sectional survey was conducted to assess the relationship between treatment and outcomes of patients with HAE type 1/2 prescribed LTP or ODT alone in a real-world setting.
• 162 physicians reported data for 601 patients from Europe and the United States, collected via the Adelphi HAE Wave II Disease Specific Programme™ (DSP).
• Of the 601 patients, 41% were taking LTP, and 59% were taking ODT alone.
  Study results showed that patients with HAE prescribed LTP in the last 12 months experienced more mild attacks than moderate or severe attacks and had significantly better health related quality of life at the time of the survey compared with those prescribed ODT alone.
• Analysis suggests that both LTP and ODT play important roles in HAE management and corroborates international guidelines that recommend patients with HAE on LTP must always have ODT available at all times.

On-Demand

Long-Term Safety and Efficacy of Oral Deucrictibant for Treatment of Hereditary Angioedema Attacks: Results of the RAPIDe-2 Extension Study, a thematic poster session by Henriette Farkas, M.D., Ph.D., D.Sc.

• Following the closure of Part A of RAPIDe-2, a Phase 2/3 study of deucrictibant for the on-demand treatment of HAE attacks, an analysis of 465 attacks from 19 participants, including 14 upper airway attacks from seven participants, was conducted.
• The final results from Part A of the RAPIDe-2 extension are consistent with the Phase 2 RAPIDe-1 randomized study.
• Deucrictibant continued to be well tolerated across all doses with no treatment-related treatment-emergent adverse events reported.
• The median time to onset of symptom relief was 1.1 hours, and 97.8% of attacks achieved onset of symptom relief by 12 hours.
• The median time to complete attack resolution was 10.6 hours, and 86.9% of attack achieved complete resolution at 24 hours.
• Deucrictibant data shows single-dose durability without symptom reoccurrence in most HAE attacks treated.89.2% of the attacks that achieved symptom resolution at 24 hours were treated with a single dose of deucrictibant.

Safety and Efficacy of Oral Deucrictibant for Treatment of Upper Airway and Laryngeal Hereditary Angioedema Attacks: Results from the RAPIDe-2 Extension Study, a flash talk by Anna Valerieva, M.D., Ph.D.

• The final data from Part A of the RAPIDe-2 study showed that safety and efficacy outcomes of treatment with deucrictibant IR were consistent for both HAE attacks affecting the upper airways, including laryngeal attacks, and HAE attacks occurring in other locations.
• Deucrictibant was generally well tolerated with no treatment-related treatment-emergent adverse events reported across upper airway and non-upper airway attacks.
• Fourteen upper airway attacks were treated by 7 participants; the median time to onset of symptom relief, as measured by Patient Global Impression of Change (PGI-C) of “a little better”, was 1.4 hours (n=14) for upper airway attacks and 1.1 hours for non-upper airway attacks (n=451).
• Endpoint measurements taken throughout the span of an entire attack until and including complete resolution were similar for both upper airway and non-upper airway attacks.
• Importantly, 92.9% of the upper airway attacks were treated with a single dose of deucrictibant.

Expansion Beyond HAE

Clinical Validation of a Novel Kinin Biomarker Assay for Characterization of Bradykinin-Mediated Pathologies in U.S. Subjects with Hereditary Angioedema, a flash talk by Evangelia Pardali, Ph.D.

• Assays for an early and accurate diagnosis of bradykinin-mediated angioedema are lacking.
• Cold activation of plasma from people living with HAE resulted in increased levels of bradykinin compared to cold-activated plasma of healthy volunteers. The qualified kinin assay can be used to reliably characterize a bradykinin signature in people with recurrent angioedema and could become a key tool aiding identification, study, and management of bradykinin-mediated pathologies including bradykinin-mediated angioedema.
• As presented at the 14th C1-Inhibitor Deficiency and Angioedema Workshop, the performance of the assay does not depend on availability of “fresh” plasma samples and the assay can also be applied in biobank samples for identification of people with bradykinin-mediated angioedema.

Development of a Conceptual Model Supporting a Clinical Outcome Assessment Strategy for Acquired Angioedema due to C1 Inhibitor Deficiency, a thematic poster session by Andrea Zanichelli, M.D., Ph.D.

• There are currently no approved therapies for the treatment of AAE-C1INH attacks, nor patient-reported outcome measures validated in AAE-C1INH.
• Concept elicitation and cognitive interviews were performed to develop a conceptual model of AAE-C1INH that could reveal important disease concepts supporting a clinical outcome assessment strategy, as well as evaluating the comprehension and interpretation of PGI-C, PGI-Severity (PGI-S), patient global assessment of change (PGA-C), and PGA-Status (PGA-S), and explore perceptions of meaningful change using these measures.
• One hundred percent of participants considered PGI-C “better” to be a meaningful change four hours post-treatment.
• Epidemiologic data and cognitive interviews further elucidate the unmet needs in bradykinin-mediated angioedema.