FDA says Pharvaris' HAE med is far from perfect, slaps on clinical hold

Right on the precipice of initial phase 2 readouts, Pharvaris is facing a roadblock instead as the FDA slapped clinical holds on the company’s phase 1 trials of a prospect to treat hereditary angioedema (HAE).

The company’s ongoing dose-escalation work for its softgel versions of PHA121 is on hold following an FDA review of nonclinical data, according to Pharvaris’ announcement Monday. PHA121 is the Dutch biotech’s umbrella asset to treat HAE that includes a number of different modalities the company hopes work better than the standard of care. The company’s disclosure had scant details but said the agency would send a formal letter within 30 days. In a statement, CEO Berndt Modig said the team is “fully committed” to addressing regulators’ concerns. 

The development is made more interesting by the fact that Pharvaris is essentially trying to tinker and renovate an existing drug. Modeled after Jerini's HAE med Firazyr, Pharvaris hopes its small-molecule-based meds can act faster than the competition. The company’s platform and pipeline centers around limiting bradykinin via its corresponding B2 receptor, which when activated, can result in edema and the release of fluids into surrounding tissues. 

Takeda now markets Firazyr after purchasing Shire in 2019. Before that, Shire purchased Jerini in 2008.

Pharvaris is chock full of Jerini alums, including Modig who was CFO at Jerini and CSO Jochen Knolle, Ph.D., who held the top R&D post at Jerini. In other words, the company’s leaders are familiar with the PHA121 and the science behind it. 

Nonetheless, Pharvaris will have to pump the breaks. One of the two trials on hold is a dose-ranging study among 72 participants testing the softgel capsules in three different single doses. The other trial similarly is assessing dose levels but will do so using a regimen rather than a single dose. In the company’s first-quarter earnings report, the company said it expected top-line data to be available in the fourth quarter of 2022. 

Wall Street reacted strongly with Pharvaris' shares down more than 26% as of 10:15 a.m. ET, dropping from $18.42 per share to $13.52. It’s a tough blow for Pharvaris, which has withstood much of biotech’s perilous run in the public markets. After launching at $29 per share in February 2021, the company has stabilized between $15 and $20 per share for most of 2022. 

Prior to going public, the company raised a $66 million series B round in September 2019. Second-quarter earnings have not yet be released but as of March 30, Pharvaris had just more than $194 million in cash and investments available.