The RAPIDe-3 trial met its primary endpoint and all 11 secondary efficacy endpoints, with deucrictibant providing symptom relief in a median of 1.28 hours and complete resolution in 11.95 hours
For people living with hereditary angioedema (HAE), sudden and unpredictable swelling attacks can disrupt daily life and require urgent treatment. Pharvaris is developing deucrictibant, an investigational oral therapy designed to provide rapid relief without injections. Following positive Phase 3 RAPIDe-3 results, BioPharma Boardroom speaks with Peng Lu, M.D., Ph.D., President of Pharvaris, about the treatment's clinical findings, its potential to improve the management of HAE attacks, ongoing development for preventive treatment and preparations for possible regulatory approval in the US and Europe.
Q. The Phase 3 RAPIDe-3 trial met its primary endpoint and all 11 secondary endpoints. What stands out to you most from these results, and what do they tell you about deucrictibant’s potential for treating hereditary angioedema attacks?
The results of the RAPIDe-3 study have shown that investigational deucrictibant immediate-release (IR), an orally administered bradykinin B2 receptor antagonist, stopped hereditary angioedema (HAE) attack progression and accelerated the time to complete symptom resolution. The primary endpoint and all 11 secondary efficacy endpoints were met with statistical significance, and most attacks were adequately controlled with a single oral capsule. In RAPIDe-3, deucrictibant was well tolerated with no treatment-related serious adverse events and no participants discontinuing treatment due to treatment-emergent adverse events.
Q. Deucrictibant achieved symptom relief in 1.28 hours and complete symptom resolution in 11.95 hours. How meaningful could these results be for patients, particularly those who need to manage unpredictable HAE attacks in their daily lives?
People living with HAE are seeking treatment options that offer improved symptom control and health-related quality of life, with reduced treatment burden. HAE attacks can be unpredictable, making it important that there could be on-demand treatments that can provide relief and move an attack toward resolution. In RAPIDe-3, deucrictibant IR demonstrated an early treatment response, with a median time to onset of symptom relief of 1.28 hours and median time to complete symptom resolution of 11.95 hours. We believe the ability to provide an early and sustained response through complete symptom resolution with an oral treatment has the potential to provide people living with HAE with a new treatment approach.
3. Most attacks in the study were adequately controlled with a single oral capsule. How could this oral treatment change the way patients manage HAE attacks compared with currently available therapies?
While multiple on-demand treatment options are available for HAE, unmet medical needs remain. We believe deucrictibant has potential to offer people living with HAE an additional treatment option by combining the established mechanism of bradykinin B2 receptor antagonism with oral administration. In RAPIDe-3, most attack symptoms were adequately controlled with a single oral capsule, supporting the potential for deucrictibant to provide a treatment option, if approved.
Q. The results were consistent across different patient groups, including those with varying attack severity, HAE types and use of preventive treatments. What does this consistency tell you about the potential role of deucrictibant in a broader HAE patient population?
The consistent results from RAPIDe-3 across HAE subtypes, including HAE type 1, HAE type 2, and HAE with normal C1 inhibitor, as well as across age, geographical location, concomitant long-term prophylaxis, and attack severities and locations including non-severe laryngeal, underscore the clinical relevance of antagonizing the bradykinin B2 receptor, a downstream target that stops the effects of excess bradykinin regardless of the pathways through which it is generated. The breadth of the participant population, together with the use of prespecified endpoints aligned with the Core Outcome Set recommended in the AURORA consensus, makes the RAPIDe-3 data particularly relevant to understanding the potential of deucrictibant across the broader HAE population.
Q. Pharvaris is also exploring deucrictibant for preventive treatment of HAE. How does the on-demand program fit into your broader development strategy, and what opportunities do you see for the drug across different treatment settings?
These findings represent an important step in Pharvaris’ broader clinical development strategy of investigating deucrictibant across both on-demand and prophylactic settings, with the goal of delivering treatment options that may address unmet medical needs of people living with bradykinin-mediated angioedema.
We are developing deucrictibant in two oral formulations: an immediate-release capsule for on-demand treatment and an extended-release tablet for prophylaxis across separate studies with different regulatory submission timeframes. This allows us to investigate the same molecule across complementary treatment settings, with the goal of providing people living with HAE with more choice in how they manage their disease.
Deucrictibant combines the established mechanism of bradykinin B2 receptor antagonism with the convenience of oral administration. Together, the RAPIDe-3 results and our prophylactic development program reinforce our belief in the potential of deucrictibant across HAE management. If approved across both indications, deucrictibant would offer the potential for oral treatment in both on-demand and prophylactic settings for HAE management.
Q. With regulatory applications now under review in the U.S. and Europe, what are your main priorities as you prepare for potential approval, and how are you thinking about bringing deucrictibant to patients if it receives authorization?
Pharvaris was founded with the vision of elevating the standard of care in HAE, and we are focused on ensuring we are prepared for the next stage of our evolution.
With the ongoing regulatory review of deucrictibant IR for the on-demand treatment of HAE attacks, we are continuing to support the regulatory process while preparing the organization for any potential outcomes. This includes building the capabilities needed to effectively engage with and support the HAE community.
Ultimately, our focus is on ensuring that we help support and further amplify the journey of patients with HAE and help address remaining unmet needs.
Deucrictibant is an investigational drug that has not been approved by the U.S. Food and Drug Administration or the European Medicines Agency.
