Deucrictibant set for key trial in acquired angioedema
Pharvaris says Phase 3 study to launch by end of year
Pharvaris said it’s on track to launch a pivotal Phase 3 trial of deucrictibant to treat and prevent swelling attacks in people with acquired angioedema by year-end.
The three-part study, called CREAATE, will evaluate deucrictibant’s potential as both an on-demand therapy to control active swelling as it occurs, and as a daily prophylactic therapy to prevent swelling attacks.
“Pharvaris is making meaningful progress in our ambition to address unmet needs of people living with … angioedema,” Berndt Modig, CEO of Pharvaris, said in a company press release.
The company is also on track with its ongoing placebo-controlled Phase 3 studies of deucrictibant for adults and adolescents with hereditary angioedema (HAE), ages 12 and older.
Top-line results from the fully enrolled RAPIDe-3 trial (NCT06343779) testing deucrictibant as an on-demand HAE therapy are due by the end of the year. The data are intended to support an application to U.S. regulators seeking approval for that indication, which Pharvaris anticipates submitting next year.
HAE trial continues
Meanwhile, enrollment continues in the CHAPTER-3 trial (NCT06669754), which is testing deucrictibant as a prophylactic HAE therapy. That trial is seeking around 81 participants at sites worldwide, with topline results expected next year.
The company is well positioned to deliver data supporting deucrictibant’s potential on schedule, Modig said.
In angioedema, excess fluid accumulates under the skin or mucous membranes, leading to repeated swelling attacks that can affect any part of the body.
Swelling in HAE arises from genetic mutations that result in the overproduction of bradykinin, a signaling molecule that causes blood vessels to become more permeable, allowing fluid to leak into nearby tissues.
Acquired angioedema is also associated with excess bradykinin. But this form of angioedema is caused as a result of an underlying condition, such as cancer or an autoimmune disease, that results in diminished levels of functional C1-inhibitor (C1-INH) protein. Because C1-INH usually puts the brakes on the pathway that leads to bradykinin production, its deficiency causes bradykinin levels to rise and swelling to ensue.
Deucrictibant is an oral small molecule that’s designed to block the B2 receptor, a protein through which bradykinin usually exerts its effects. This should help control and prevent swelling in all forms of bradykinin-mediated angioedema.
Pharvaris has developed two versions of the medication: an immediate-release capsule that quickly reaches therapeutic levels in the blood to control active swelling and an extended-release tablet that releases the medication more slowly to prevent swelling with once-daily dosing.
While most clinical studies have involved people with HAE, a small clinical trial tested deucrictibant in three people with acquired angioedema. Results showed that on-demand treatment with deucrictibant led to reductions in swelling attack severity, while prophylactic treatment was associated with reductions in the rate of swelling attacks.
Pharvaris said early this year that it was moving forward with plans for a Phase 3 trial in acquired angioedema.
CREAATE will enroll people with acquired angioedema due to C1-INH deficiency. In the first part, participants will receive either an extended-release deucrictibant tablet (40 mg) or a placebo once daily to evaluate the therapy’s potential as a prophylactic treatment.
For the trial’s second part, each participant will treat two attacks — one with an immediate-release deucrictibant capsule (20 mg) and one with a placebo — to evaluate the therapy as an on-demand treatment.
The third and final part is an open-label extension that will evaluate the long-term safety and efficacy of immediate-release deucrictibant as an on-demand therapy.
Deucrictibant has been granted orphan drug designation in the U.S. and European Union to treat bradykinin-mediated angioedema. The designation is intended to help speed the drug’s clinical development for these indications.
About the Author
