Deucrictibant granted orphan drug status in EU for angioedemas
Therapy designed to treat diseases linked to bradykinin overproduction
Deucrictibant, an oral therapy being developed for bradykinin-mediated diseases such as hereditary angioedema (HAE) and acquired angioedema, has been granted orphan drug status in the European Union.
This designation, granted by the European Commission, intends to back the development of therapies to diagnose, prevent, or treat rare diseases — those affecting fewer than 5 in 10,000 people in the EU — or treatments whose marketing is unlikely to generate enough funds to justify investing in its development. With orphan drug status, Pharvaris, the therapy candidate’s maker, may receive assistance from the European Medicines Agency and fee reductions, as well as 10 years of marketing exclusivity if deucrictibant is ultimately approved.
The European Commission’s decision follows by about three years the U.S. Food and Drug Administration’s similar granting of orphan drug status to the treatment.
“By granting deucrictibant orphan designation for the treatment of bradykinin-mediated angioedema, the European regulators are acknowledging deucrictibant’s ability … to address the unmet needs associated with any bradykinin-mediated angioedema condition,” Peng Lu, MD, PhD, chief medical officer at Pharvaris, said in a company press release.
Deucrictibant being developed as both on-demand, preventive therapy
Bradykinin is a signaling molecule that regulates blood pressure and inflammation by causing blood vessels to widen and become permeable.
In HAE, genetic mutations lead to the overproduction of bradykinin, triggering angioedema attacks marked by rapid swelling that can arise anywhere in the body. Acquired angioedema occurs due to an underlying disorder, such as certain autoimmune diseases or cancers, that disrupts the function of C1-inhibitor (C1-INH), a protein that regulates bradykinin production. Without enough C1-INH, bradykinin levels rise, causing swelling.
Deucrictibant is a small molecule designed to block the bradykinin receptor called B2, which is intended to prevent bradykinin from triggering blood vessel leakage and thus controlling swelling attacks.
Pharvaris is developing two oral formulations: an immediate-release capsule called PHVS416 for on-demand treatment, and an extended-release tablet dubbed PHVS719 as a prophylactic, or preventive, agent.
“By blocking the effects of bradykinin, the ultimate culprit inducing angioedema attacks, regardless of its source, deucrictibant has the potential to offer a broader-acting option to address the unmet need associated with bradykinin-mediated angioedema diseases, beyond HAE,” Lu said.
Therapy being tested for HAE in Phase 2, 3 clinical trials
The therapy is now undergoing evaluation in a series of clinical studies. The Phase 2 CHAPTER-1 trial (NCT05047185) and its long-term extension study are assessing it as a preventive therapy for HAE attacks. Meanwhile, the Phase 2 RAPIDe-1 (NCT04618211) and its long-term extension RAPIDe-2 (NCT05396105) are testing deucrictibant as an on-demand HAE treatment.
Data from CHAPTER-1 showed that prophylactic treatment significantly reduced the rate of swelling attacks relative to a placebo, with benefits sustained during its extension study. Relative to the start of CHAPTER-1, attack rates dropped by 93% after a year in the extension study.
RAPIDe-1 trial results showed that on-demand deucrictibant outperformed a placebo in easing skin pain, swelling, and abdominal pain, with a markedly faster time to symptom relief. In the extension study, attack severity was lessened after a median of 2.6 hours, with nearly all attacks (97.7%) showing reduced severity by 12 hours.
We are diligently executing our Phase 3 development program evaluating the efficacy and safety of deucrictibant in HAE. … [Further,] we are currently discussing a pivotal trial in [acquired angioedema] with regulators.
Building on the success of these findings, the company has been testing deucrictibant in a pair of Phase 3 trials.
The CHAPTER-3 (NCT06669754) trial expects to enroll about 81 HAE patients to test PHVS719 as a prophylactic treatment, with results expected in the second half of 2026. The RAPIDe-3 (NCT06343779) study will assess PHVS416 as an on-demand treatment for swelling attacks in up to 120 HAE patients. Top-line data from this trial is expected in early 2026.
A third open-label long-term extension Phase 3 trial, CHAPTER-4 (NCT06679881), will enroll an estimated 130 HAE patients, including those who participated in CHAPTER-1 or may have rolled over from CHAPTER-3.
Pharvaris also plans to pursue the clinical development of deucrictibant in acquired angioedema. That decision was based on promising clinical data that showed the treatment reduced attack severity and the rate of monthly attacks in three patients.
“Today, we are diligently executing our Phase 3 development program evaluating the efficacy and safety of deucrictibant in HAE,” Lu said. Moreover, “we are currently discussing a pivotal trial in [acquired angioedema] with regulators.”
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