The US Food and Drug Administration (FDA) has placed a clinical hold on the clinical trials of PHA121, an experimental treatment for hereditary angioedema (HAE).

According to a news release from the drug’s developer, Pharvaris, the FDA verbally informed the company of the clinical hold based on its review of nonclinical data. The FDA stated that a formal clinical hold letter will be provided in approximately 30 days.

The hold applies to the US clinical trials of PHA121 covered under 2 Investigational New Drug (IND) applications: NCT04618211, NCT05047185, and NCT05396105.

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“We are fully committed to working closely with the FDA to address the agency’s concerns,” Berndt Modig, chief executive officer of Pharvaris, said. “Pharvaris remains dedicated to providing new therapeutic choices for the treatment of HAE and is working diligently to bring PHA121 to people living with HAE.”

Read more about experimental therapies for HAE.

HAE is most commonly a result of insufficient levels or lack of function of the C1 esterase inhibitor (C1-INH) protein, which usually inhibits the plasma kallikrein enzyme. Without sufficient inhibition, plasma kallikrein causes an increase in bradykinin levels which bind to the bradykinin B2-receptor in blood vessels and lead to HAE attacks.

PHA121 is a novel, oral bradykinin-B2-receptor antagonist designed to both treat and prevent HAE attacks. By binding and blocking the bradykinin B2 receptor through competitive antagonism, PHA121 prevents the occurrence of attacks.

According to Pharvaris, PHA121 has previously demonstrated selective and highly potent antagonism of the B2 receptor in preclinical studies. In clinical study data already collected, the drug showed “rapid and potent activity at multiple oral doses in a bradykinin-mediated challenge model” and was observed to be safe and well-tolerated at those doses.

Pharvaris is currently developing 2 formulations that include PHA121 including a soft gel capsule called PHVS416 for prophylaxis and on-demand treatment as well as a tablet formulation called PHVS719 for prophylaxis.


Pharvaris announces FDA clinical hold on PHA121 clinical trials in the US. News release. Pharvaris; August 22, 2022.

Therapeutic focus. Pharvaris. Published June 8, 2020. Accessed August 25, 2022.

Pipeline. Pharvaris. Published June 8, 2020. Accessed August 25, 2022.