Phase 3 trial to test extended deucrictibant as treatment for HAE
Pharvaris also aims to test therapy for acquired angioedema
Pharvaris said it plans to initiate a Phase 3 clinical trial by the end of the year to test an oral, extended-release tablet formulation of deucrictibant as a preventive, or prophylactic, treatment for hereditary angioedema (HAE).
Called CHAPTER-3, the trial will assess the treatment’s safety and efficacy in reducing HAE attacks. The extended-release formulation, PHVS719, maintains blood levels of deucrictibant above the therapeutic threshold for 24 hours, meaning it can be taken once daily to provide sustained protection against HAE attacks.
The trial “enables us to evaluate deucrictibant’s ability to address the need for improvements in quality of life that people living with HAE want and deserve: a therapy providing injectable-like efficacy, from the first day of therapy, with a favorable tolerability and the convenience of once-daily oral administration,” Stefan Abele, PhD, Pharvaris’ chief technical operations officer, said in a company press release.
The company also said it intends to pursue the clinical development of deucrictibant in another type of angioedema, called acquired angioedema. The decision followed promising data from a small study conducted by researchers in Amsterdam showing the treatment was able to reduce attack severity and the rate of monthly attacks in three patients.
“There is an unmet need for therapies approved specifically for the treatment of [acquired angioedema],” said Remy S. Petersen, MD, researcher at the Amsterdam University Medical Center. University researchers were “pleased to confirm” their hypothesis that deucrictibant “has the potential to successfully prevent and treat” the disease, and they “look forward to continuing our collaboration with Pharvaris” on clinical development of the therapy, Petersen said.
Small molecule as treatment for HAE
Angioedema occurs when fluid builds up beneath the skin or mucous membranes, resulting in swelling attacks.
In HAE, this is usually caused by genetic mutations that impair the production or function of a protein called C1-inhibitor (C1-INH), leading to the excessive production of bradykinin, a signaling molecule that causes blood vessels to widen and leak fluid to surrounding tissues.
In acquired angioedema, swelling attacks are also caused by a deficiency in C1-INH and a subsequent increase in bradykinin levels. However, unlike HAE, genetic mutations are not the root cause of acquired angioedema. Instead, this type of angioedema usually arises as a consequence of another underlying disorder, such as cancer or an autoimmune disease.
Deucrictibant is a small molecule that’s designed to block the bradykinin B2 receptor, preventing bradykinin from exerting its action in blood vessels and triggering swelling. Besides the extended-release formulation, the therapy is available in an immediate-release capsule formulation, PHVS416, that allows it to rapidly reach therapeutic levels in the blood.
Recently announced data from the extension portions of two Phase 2 trials evaluating the safety and efficacy of deucrictibant as a prophylactic and on-demand treatment for HAE attacks showed the therapy was able to maintain the rate of attacks low in the long term, as well as rapidly resolve those that did occur.
“Given the totality of data for deucrictibant, now bolstered by new data from ongoing long-term extension studies showing tolerability and efficacy in both prophylaxis and on-demand treatment, we believe deucrictibant has the potential to become a preferred therapy for the management of HAE,” said Berndt Modig, Pharvaris’ CEO.
The company earlier this year announced the launch of a separate Phase 3 trial, RAPIDe-3 trial (NCT06343779), which is evaluating the efficacy and safety of deucrictibant immediate-release capsules to treat HAE attacks.
“We remain focused on the efficient execution of our clinical studies, with the CHAPTER-3 study expected to initiate by the end of the year while RAPIDe-3 is progressing as planned,” said Modig. “Pharvaris has the expertise to expand deucrictibant beyond HAE to other bradykinin-mediated-disease — such as [acquired angioedema] — and we are excited to explore the potential for deucrictibant to meet a currently unaddressed medical need.”
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