Pharvaris presents data at the Bradykinin Symposium 2024
Pharvaris announced a summary of data being presented at the ongoing 7th Bradykinin Symposium. Details of the presentations are outlined below:
Long-term safety and efficacy of oral deucrictibant for HAE prophylaxis
A poster presentation by Marc A Riedl MD MS. In the current analysis of the ongoing open-label extension of the CHAPTER-1 Phase 2 study, deucrictibant 40 mg/day was well-tolerated, with no new safety signals observed. The results presented provide evidence of the long-term safety and efficacy of deucrictibant for the prevention of HAE attacks and support further development of deucrictibant as a potential prophylactic therapy for HAE. Results of this analysis provide support that:
- Continuing deucrictibant treatment sustained the early-onset attack reduction seen in the randomized, placebo-controlled portion of the trial, with a median attack rate of zero for every month for over a year in the open-label part of the study
- On average, less than one attack per year per participant was treated with on-demand medication
Treatment of HAE attacks with oral deucrictibant: RAPIDe-2 extension results
A poster presentation by Emel Aygören-Pürsün MD. In the current analysis of the ongoing RAPIDe-2 Phase 2/3 extension study, deucrictibant immediate release capsule was well-tolerated for all studied doses with no new safety signals observed. Results from the ongoing RAPIDe-2 extension are consistent with the randomized, placebo-controlled RAPIDe-1 Phase 2 study and provide evidence regarding the long-term safety and efficacy of deucrictibant IR capsule for repeat treatment of HAE attacks. Outcome analyses showed:
- Median time to onset of symptom relief as measured by the Patient Global Impression of Change (PGI-C) was 1.1 hours, with 98.5% of attacks achieving onset of symptom relief by 12 hours
- Median time to reduction in attack severity as measured by the Patient Global Impression of Severity (PGI-S) was 2.6 hours, with 97.7% of attacks achieving reduction in attack severity by 12 hours
- Median time to complete attack resolution as measure by PGI-S was 11.5 hours, with 85.8% of attacks achieving complete attack resolution within 24 hours
- Overall, 86.0% of attacks were treated with a single dose of deucrictibant immediate-release capsule
Prophylactic treatment with deucrictibant improves HAE disease control and HRQoL
An oral presentation by Markus Magerl MD. In the randomized, placebo-controlled part of CHAPTER-1, a Phase 2 clinical study of deucrictibant for the prophylactic treatment of HAE attacks, health-related quality of life was evaluated using several measures. In the study, it was demonstrated that deucrictibant treatment led to improvements in disease control versus placebo, with 90% of participants in the deucrictibant-groups demonstrating well-controlled HAE at week 12. Presentation details included:
- Deucrictibant improved Angioedema Quality of Life Questionnaire (AE-QoL) scores, particularly in “functioning” and “fear/shame” domains compared to placebo
- Deucrictibant-treated participants reported greater satisfaction than those treated with placebo with regards to effectiveness and the domain of global satisfaction, and a comparable satisfaction for side effects, as measured by Treatment Satisfaction Questionnaire for Medication (TSQM)
Deucrictibant vs. standard of care in HAE: Propensity score-matched analysis
A poster presentation by Marc A Riedl MD MS. A propensity score-matched comparison of clinical outcomes between a subgroup of attacks (N=73) from the RAPIDe-2 study and a subgroup of attacks (N=73) from an observational real-world study treated with standard of care, the outcomes were more favorable for the attacks treated with deucrictibant on PGI-C- and PGI-S-based assessments. Deucrictibant had a shorter (1.07 hours) median time to onset of symptom relief as measured by PGI-C “a little better” compared to standard of care (2.38 hours).
Cardiovascular safety of repeated oral administration of the B2-receptor antagonist deucrictibant
A poster presentation by Nieves Crespo PhD. In chronic nonclinical safety studies of deucrictibant in non-human primates, no evident effects on cardiac electrophysiology, morphology and hemodynamic parameters were observed. Deucrictibant has showed no evident effects on cardiac electrophysiology and hemodynamic parameters in clinical studies in humans to date, following prophylactic treatment up to 12 weeks of administration in the randomized, placebo-controlled part of the Phase 2 CHAPTER-1 clinical study and up to one year of mean duration of treatment in the ongoing open-label extension (OLE) part.
Prophylaxis of hereditary angioedema attacks with oral deucrictibant: CHAPTER-1 results
A poster presentation by Emel Aygören-Pürsün MD. The CHAPTER-1 study demonstrated that deucrictibant may significantly reduce the occurrence of HAE attacks, and clinically meaningful reduction in occurrence of moderate and severe HAE attacks, as well as HAE attacks treated with on-demand medication, was observed. CHAPTER-1 results provide evidence of the efficacy and safety of deucrictibant for the prevention of HAE attacks and support its further development as a potential prophylactic therapy for HAE.
Clinical trials conformity with AURORA COS: a systematic literature review
A poster presentation by Remy S Petersen MD. Conforming to a core outcome set (COS) across various study designs, such as the COS recommended for HAE clinical studies by the Panel of Experts participating in the AURORA Project, may homogenize the use of specific outcomes for clinical studies and support future indirect comparisons among interventions. The design of the RAPIDe-3 Phase 3 study of deucrictibant immediate-release capsule for the on-demand treatment of HAE attacks fully conforms with the AURORA COS based on its prespecified endpoints.
Bradykinin challenge model in humanized bradykinin B2 receptor transgenic rat
An oral presentation by Jolanta Skarbaliene PhD. The bradykinin (BK) challenge model is a tool to assess pharmacokinetic and pharmacodynamic activity of bradykinin B2 receptor antagonists. A BK challenge model was successfully developed in humanized bradykinin B2 receptor transgenic rats that are pharmacologically responsive to bradykinin B2 receptor antagonists. The BK challenge model in humanized bradykinin B2 receptor transgenic rats can offer a valuable, easy to manage, and cost-effective tool for efficacy studies compared to those involving non-human primates.
Deucrictibant inhibits carrageenan-induced edema in bradykinin B2 receptor transgenic rat
A poster presentation by Anne Lesage PhD. A humanized bradykinin B2 receptor transgenic rat model was used to address the challenge of deucrictibant species selectivity in experimental models. Oral deucrictibant inhibited carrageenan-induced paw edema in humanized bradykinin B2 receptor transgenic rats.
The bradykinin challenge model translates across rat, monkey and human,
A poster presentation by Juan Bravo PhD. The pharmacokinetics (PK) and pharmacodynamics (PD) of icatibant were analyzed from BK challenge studies in humanized bradykinin B2 receptor transgenic rats, non-human primates, and healthy volunteers. Analyses across species showed similar responses, demonstrating that the BK challenge model in transgenic rats and non-human primates may be predictive of PK/PD outcomes in humans.
A novel kinin biomarker assay for characterization of bradykinin-mediated disorders
A poster presentation by Evangelia Pardali, PhD. BK is involved in various physiological and pathological processes, including angioedema (AE). Differentiating BK-mediated from histamine-mediated AE and assessing the role of BK in the pathogenesis of other conditions by measuring kinin peptides remains a challenge due to their proteolytic instability and limitations of current analytical assays. A kinin biomarker assay was established and qualified, which could become a key tool for identifying, studying, and managing BK-mediated diseases.
A HMWK capillary immunoblotting assay to characterize bradykinin-mediated disorders
A poster presentation by Evangelia Pardali PhD. Activation of the plasma kallikrein-kinin system (KKS) can result in cleavage of high molecular weight kininogen (HMWK) and production of vasodilatory kinins, such as BK. A HMWK immunoblotting assay was established and qualified to reliably measure KKS biomarkers in human plasma and could become a key tool for identifying, studying, and managing BK-mediated diseases.
(Source: Pharvaris)