Pharvaris hits a snag with hereditary angioedema pill as FDA places hold on trials
Swiss biotech Pharvaris announced Monday that the FDA has placed a hold on the clinical trials for its oral drug PHA121 which aims at treating hereditary angioedema, or HAE, a rare genetic condition.
The regulators placed the hold after reviewing the company’s nonclinical data, Pharvaris said. The FDA’s decision is a setback for the company’s Phase II study, which aims to evaluate the efficacy and safety of the drug.
Pharvaris is among the few companies to develop an oral drug for HAE, a disease characterized by painful swelling in hands, feet, and occasionally in the airways or intestinal walls. While effective therapies already exist, such as CSL’s Haegarda and Takeda’s Cinryze, Takhzyro and Firazyr, all of them are injectables.
HAE is caused by a deficiency in the blood plasma protein C1 esterase inhibitor, and both Haegarda and Cinryze try to boost the level of that protein in the blood. Firazyr, on the other hand, blocks bradykinin, a blood protein that is overproduced in HAE because of increased levels of C1. Elevated levels of bradykinin cause blood cells to leak and tissues to swell.
Pharvaris’ drug PHA121 is an oral pill that works as a bradykinin B2 receptor antagonist. Phase I data from 16 healthy volunteers suggest their molecule is 24 times as potent as Firazyr, and the company has already launched two Phase II trials: one for prophylaxis and one for treating acute pain.
Other companies have tried to develop oral therapies for HAE, but so far only one has crossed the FDA finish line. BioCryst’s Orladeyo, approved in December 2020, passed a Phase III trial, with the higher dose reducing the angioedema attack rate by 44% versus placebo (p<0.001), while the lower dose cut the attack rate by 30% (p=0.024).
Though analysts were left unimpressed at the time after suggesting that the drug needed least a 50% reduction of attack rate to ensure competitiveness, Orladeyo sales figures have been on the rise. After pulling in $121.6 million last year, the drug netted BioCryst $114.9 million in the first half of this year alone, the biotech reported.
Meanwhile, Pharvaris CEO Berndt Modig said the company was working closely with the FDA to address the agency’s concerns. The company’s stock $PHVS fell nearly 20% on Monday after the company announced the hold.
Pharvaris was founded by Modig, and other veterans from Jerini, the biotech that originally developed Firazyr. In November 2020, the company raised an $80 million Series C led by Viking Global Investors and General Atlantic.
Editor’s note: This article has been updated to clarify that BioCryst’s Orladeyo was approved in December 2020.