Pharvaris' Deucrictibant: A Groundbreaking Oral Therapy Poised to Disrupt Hereditary Angioedema Treatment

Hereditary angioedema (HAE) remains a rare but debilitating condition with limited treatment options, despite decades of research. Now, Pharvaris' deucrictibant—a novel oral bradykinin B2 receptor antagonist—is poised to redefine the standard of care. With Phase 3 data nearing completion and a dual-formulation strategy targeting both prophylaxis and on-demand treatment, deucrictibant could disrupt the HAE market by offering unparalleled convenience, efficacy, and safety.

The Clinical Case for Disruption

HAE is characterized by recurrent, unpredictable attacks of severe swelling caused by a deficiency in the C1 inhibitor protein. Current treatments, such as Firazyr (icatibant) and Cinryze (C1 esterase inhibitor), require frequent injections, which many patients find burdensome. Deucrictibant's oral formulation addresses this unmet need, positioning it as a potential first-in-class therapy.

Prophylactic Efficacy:
Data from the Phase 2 CHAPTER-1 trial and its open-label extension (OLE) demonstrate that once-daily deucrictibant (40 mg) reduced monthly attack rates to near-zero levels. In the OLE phase, 30 patients maintained a median of zero days with symptoms over 12.8 months of treatment, with some exposed to the drug for up to 23.7 months. This sustained efficacy is critical, as long-term prophylaxis is linked to better health-related quality of life (HRQoL) and reduced severe attacks compared to on-demand therapies alone.

On-Demand Breakthroughs:
The RAPIDe-2 extension study highlights deucrictibant's rapid action. In 337 attacks (including seven life-threatening upper airway cases), the median time to symptom relief was 0.9–1.1 hours, with 85–86% of attacks resolved with a single dose. For upper airway attacks—a major cause of mortality—the median time to relief was just 0.9 hours, outperforming existing injectable on-demand therapies like Firazyr.

Market Opportunity and Competitive Landscape

The global HAE market is projected to reach $2.5 billion by 2030, driven by growing awareness and unmet needs. Current therapies, such as Shire's Cinryze (now owned by Takeda) and BioCryst's oral icatibant (Byluterol), face limitations: Cinryze requires weekly infusions, while Byluterol's efficacy is less proven in severe attacks. Deucrictibant's dual-formulation approach—combining once-daily prophylaxis with rapid on-demand treatment—could capture ~40–50% market share within five years post-approval.

Further, Pharvaris is exploring deucrictibant's use in acquired angioedema (AAE-C1INH), a larger patient population, potentially tripling its addressable market.

Risks and Regulatory Hurdles

While the data is promising, risks remain. Phase 3 trials (CHAPTER-3 and RAPIDe-3) must confirm these findings in larger, randomized cohorts. The RAPIDe-3 trial's novel “end-of-progression” endpoint—measuring complete attack resolution—could complicate FDA review, though positive data from RAPIDe-2 bodes well. Additionally, competition from emerging therapies, such as Bioverativ's lanadelumab (a subcutaneous prophylactic), may pressure pricing.

Investment Thesis

Pharvaris' stock (PVRS) has surged +120% since 2023 on early clinical data, but the Phase 3 readouts in late 2025/early 2026 will be pivotal. A successful outcome could catalyze a +200% upside, pushing PVRS to $150–$200 per share. However, investors should note that regulatory delays or safety issues in Phase 3 could lead to a sharp correction.

Final Analysis

Deucrictibant has the potential to transform HAE treatment by delivering oral convenience and efficacy unmatched by current therapies. With robust Phase 2 data and a focused development strategy, Pharvaris is well-positioned to disrupt an underserved market. Investors seeking exposure to rare-disease therapies with high clinical and commercial impact should consider initiating a position ahead of Phase 3 results, with a risk-aware approach to potential volatility.

Final recommendation: Buy PVRS with a 12–18 month horizon, targeting $180/share. Set a stop-loss at $80 to mitigate trial failure risk.