Pharvaris (PHVS) presented new clinical data on its oral hereditary angioedema (HAE) treatment deucrictibant at the Wells Fargo 21st Annual Healthcare Conference, highlighting an 87% reduction in attacks among Type 1 and Type 2 HAE patients in the Phase III CHAPTER-3 prophylaxis study.
The results, delivered during a session moderated by Wells Fargo biotech analyst Yanan Zhu, featured CEO and co-founder Berndt Modig and President Peng Lu alongside Chief Commercial Officer Wim Souverijns.
Deucrictibant, an oral B2 receptor antagonist being developed in both on-demand and prophylaxis formulations, was compared directly against existing injectable treatments including Icatibant, Orladeyo, and Takhzyro. Modig noted the attack reduction matched or approached levels seen with injectable alternatives.
"If you really compare with the patient population, type 1 and type 2 of hereditary angioedema, which is what is covered by the other injectables, we're right up there with 87% attack reduction," Modig said.
The CHAPTER-3 trial enrolled 83 patients across six continents — North America, Europe, Asia Pacific, Latin America, and South Africa — marking the first HAE pivotal trial to span all six regions. Patients on placebo experienced approximately 2.6 attacks per month. Eighty out of 83 patients, or 96.4%, subsequently rolled over into the CHAPTER-4 open-label extension study.
For the on-demand formulation, Pharvaris reported a time to minimal improvement of 1.28 hours, versus roughly two hours for icatibant. Complete resolution occurred in under 12 hours with deucrictibant, compared to more than 24 hours for icatibant. Approximately 17% of patients required a second dose with deucrictibant, versus about 40% with the injectable comparator.
Souverijns emphasized the pharmacokinetic profile, noting that morning dosing provides sufficient drug levels by afternoon to prevent attacks. "So that is why we strongly believe that the oral segment ultimately will be largely dominated by deucrictibant," he said.
Pharvaris also pointed to potential market opportunity beyond Type 1 and 2 HAE. An estimated 15% to 25% of the HAE population has normal C1INH levels, a group that could be addressed by the drug's acquired angioedema indication. Top-line data from the CREAATE trial in acquired angioedema is expected in the first quarter of 2025.
Modig reflected on the decade-long development journey, noting deucrictibant has been in development for 10 years and four months. He and his co-founder entered the HAE space 23 years ago working on icatibant.
The FDA has set a PDUFA date of April 23 for the on-demand formulation. Pharvaris plans to file the prophylaxis version in the first half of 2025.
Safety data from CHAPTER-3 showed Grade 2 liver enzyme elevations in two patients, measured at roughly five times the upper limit of normal. Steady state was reached in two to three days of once-daily dosing.
Real-world evidence for competitor Orladeyo cited in the discussion showed a 40% dropout rate, with patients still experiencing six to 12 breakthrough attacks per year while on long-term therapy. Approximately 150 to 250 new patients are added to long-term prophylaxis annually.
