Deucrictibant trial for acquired angioedema in sight, Pharvaris says
Clinical testing to advance as data show promise
Pharvaris plans a trial of deucrictibant to treat acquired angioedema this year, following promising data showing the experimental oral small molecule helped to stop or prevent swelling attacks in three patients.
The company has been testing deucrictibant in a pair of Phase 3 trials, CHAPTER-3 (NCT06669754) and NRAPIDe-3 (NCT06343779). A third, CHAPTER-4 (NCT06679881), is on track to start this year.
“Pharvaris is committed to generating robust clinical data to build a compelling package supporting deucrictibant’s efficacy and safety profile,” Berndt Modig, Pharvaris’ CEO, said in a company press release. “Our team is focused on the execution of two Phase 3 clinical studies in HAE, the expansion of our pipeline into [acquired angioedema], and preparations for commercialization of deucrictibant pending regulatory submission and approval.”
Last year, the company launched CHAPTER-3, a Phase 3 clinical trial that’s testing an extended-release tablet formulation of deucrictibant as a prophylactic treatment to prevent swelling attacks in adults and adolescents with hereditary angioedema (HAE), ages 12 and older.
CHAPTER-3 aims to enroll about 81 participants, who will be randomly assigned to receive either a 40 mg extended-release tablet of deucrictibant or a placebo, once daily for 24 weeks, or about six months. Its main goal is to assess deucrictibant’s ability to reduce the number of HAE swelling attacks over the course of six months of treatment. Results are expected in the second half of 2026, according to Pharvaris.
Hereditary vs acquired angioedema
RAPIDe-3, which is testing an immediate-release capsule formulation of deucrictibant for treating HAE swelling attacks as they occur, is progressing on schedule, the company said. It expects top-line data from that trial in early 2026. HAE patients ages 12 and older will use a 20 mg immediate-release capsule of deucrictibant or a placebo, given in a random order, to treat two attacks. The main goal of the study, which is expected to enroll up to 120 participants, is to assess deucrictibant’s ability to shorten the time to onset of symptom relief.
Angioedema occurs when fluid builds up beneath the skin or mucous membranes, resulting in repeated attacks of swelling. In HAE, this is due to genetic mutations that lead to the overproduction of a signaling molecule called bradykinin. Too much bradykinin causes blood vessels to become more permeable and leak fluid into tissues.
Unlike HAE, acquired angioedema doesn’t have a genetic cause. Instead, it occurs as a result of an underlying condition, usually cancer or an autoimmune disease, that causes levels of a protein called C1-inhibitor (C1-INH) to drop. Without enough C1-INH, bradykinin levels increase, leading to swelling.
Deucrictibant is a small molecule designed to block the B2 receptor for bradykinin. This prevents bradykinin from interacting and sending signals through its B2 receptor, which is expected to bring swelling under control.
PHVS416, the immediate-release capsule formulation of deucrictibant, is expected to quickly reach a therapeutic level in the blood. It is being tested as an on-demand treatment to control attacks of swelling as they occur. PHVS719, the extended-release tablet formulation, is designed to release deucrictibant slowly over the course of 24 hours, allowing for once-daily dosing for prophylaxis.
This year, Pharvaris plans to start CHAPTER-4, an open-label long-term extension study that will evaluate the safety and efficacy of deucrictibant’s extended-release tablet formulation for the prophylactic treatment of HAE attacks. The study will enroll HAE patients ages 12 and older, including those who participated in the Phase 2 CHAPTER-1 trial (NCT05047185) or who may have rolled over from CHAPTER-3.
The company also said RAPIDe-2 (NCT05396105), a Phase 2/3 open-label extension evaluating the long-term safety and efficacy of deucrictibant’s immediate-release capsule for the on-demand treatment of HAE swelling attacks, is ongoing. The two-part extension study is open to patients who participated in a previous Phase 2 clinical trial called RAPIDe-1 (NCT04618211), as well as to those who took part in RAPIDe-3.
“This year is paramount to Pharvaris as we continue clinical development of deucrictibant to help address unmet needs for those living with bradykinin-mediated angioedema,” Modig said.
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