Pharvaris oral HAE drug cuts attacks by 83% in Phase 3
Switzerland-based Pharvaris’ once-daily oral deucrictibant XR reduced hereditary angioedema (HAE) attacks by 83% versus placebo in a pivotal Phase 3 trial, putting the experimental prophylactic into roughly the same efficacy range as several leading injected treatments.
Why it matters: HAE is a rare genetic disorder that causes unpredictable, potentially life-threatening swelling attacks, typically driven by excessive bradykinin activity.
- Preventive treatment can sharply reduce those attacks, but oral convenience has so far come with an efficacy trade-off. BioCryst’s Orladeyo, currently the main oral prophylactic option, reduced attacks by 44% versus placebo at its approved 150 mg dose in Phase 3. Pharvaris’ result suggests that gap could narrow considerably.
Zoom in: CHAPTER-3 enrolled 85 adolescents and adults across 21 countries, with 55 receiving deucrictibant XR 40 mg once daily and 30 receiving placebo for 24 weeks. The drug reduced the mean monthly attack rate by 83%, meeting the primary endpoint.
- Among the 80 patients with the more common Type 1 or Type 2 HAE, the reduction reached 87%. Pharvaris also said all prespecified secondary efficacy endpoints were met, including measures of moderate or severe attacks, use of on-demand medication and attack-free status. Quality-of-life scores improved significantly versus placebo.
How it compares: On a mean placebo-adjusted basis, deucrictibant’s efficacy sits squarely in the range reported for leading injectable prophylactics.
- Takeda’s Takhzyro reduced attacks by about 87% versus placebo at 300 mg every two weeks in the HELP study. CSL Behring’s once-monthly Andembry produced an adjusted reduction of about 89% in VANGUARD, while monthly Dawnzera from Otsuka/Ionis achieved about 81%.
- HAEGARDA is frequently associated with a 95% reduction, but that figure refers to the median reduction in attacks. On the more comparable mean measure, its Phase 3 COMPACT result was about 84% versus placebo.
Yes, but: Treatment-emergent adverse events occurred in 76.4% of deucrictibant-treated patients versus 56.7% on placebo, although most were mild or moderate and no treatment-related serious adverse events were reported. During the data webcast, Pharvaris disclosed two Grade 3 liver-enzyme elevations; one patient discontinued treatment while the other completed the study.
The big picture: The prophylaxis bar is still moving. Intellia Therapeutics’ one-time CRISPR therapy lonvoguran ziclumeran also reduced attacks by 87% versus placebo in Phase 3, with 62% of treated patients remaining attack- and therapy-free over the six-month efficacy period. Its U.S. application is now under FDA review. BioCryst, meanwhile, is developing navenibart as an injectable that could be given only every three or six months.
- Pharvaris is also developing an immediate-release version of deucrictibant for acute attacks. The FDA is reviewing that formulation with an April 23, 2027 decision date, putting it on course to challenge KalVista’s Ekterly, the first approved oral on-demand HAE treatment.
Investors liked the readout: Pharvaris shares rose 7.35% on Sept. 8 to close at $37.84 after touching a 52-week high of $43.25 during the session. Analyst firm Oppenheimer subsequently raised its price target from $50 to $75, arguing the efficacy matched the Phase 2 data and the profile of Takhzyro.
What’s next: Pharvaris plans to file deucrictibant XR for prophylaxis starting in the first half of 2027, while the CHAPTER-4 long-term extension continues. More detailed CHAPTER-3 efficacy and safety data are due at future medical meetings.
