KalVista ends a PhII study early after patients suffer severe and life-threatening side effects
KalVista took a beating Tuesday after announcing it would scrap a Phase II trial for one of its experimental drugs.
The biotech said in an early morning press release that it is terminating the study for KVD824 after multiple patients in every treatment group saw unsafe, elevated levels of certain liver enzymes. By ending the trial now, KalVista hopes to save some money and funnel it toward another study for its lead program, CEO Andrew Crockett said in a statement.
Investors were not pleased with the news, as KalVista shares $KALV took a beating when the market opened. The biotech’s stock lost more than half its value, falling 52% in early Tuesday trading.
KVD824 is an “oral plasma kallikrein inhibitor,” KalVista said, designed to treat adults with a rare genetic disorder called hereditary angioedema that causes fluid to build up outside blood vessels and block patients’ normal blood flow. Researchers randomized trial participants to one of three dose levels — 300 mg, 600 mg or 900 mg — and instructed them to take the drug twice a day.
Among the 33 patients who took the drug, seven reported Grade 3 (severe) or Grade 4 (life-threatening) side effects of liver enzyme elevation. The adverse events took place across a wide timeframe ranging from two to 12 weeks post-trial start, KalVista said. Another life-threatening event was seen in a separate patient before they started taking KVD824.
Though these safety issues would appear to doom KVD824’s development prospects, KalVista said in its press release it would need to finish wrapping up data collection and examine the full unblinded datasets before making a final determination. In an analyst note out late Tuesday morning, Jefferies’ Maury Raycroft described the result as “disappointing” and said his conversations with execs revealed they are still working to determine the relationship between baseline liver enzymes and HAE severity.
This is not the first time KVD824 has run into roadblocks. Last year, the FDA placed the program on clinical hold after requesting additional preclinical data and telling the biotech to amend its Phase II study protocol. The hold was lifted in September 2021, and Crockett said at the time that the study changes were “relatively straightforward.”
But with the drug falling flat in Phase II — with some serious safety concerns to boot — KalVista could be giving up a challenge in this space to the Dutch biotech Pharvaris. Analysts had keyed in on this race between the two companies, expecting a photo finish at the FDA. SVB Securities’ Joseph Schwartz wrote last year that it wasn’t clear which drug would be the first approved.
Pharvaris, however, has run into its own brick wall at the agency. In August, regulators slapped a hold on the biotech’s studies after asking for more preclinical data. Whereas KalVista’s drug worked to inhibit plasma kallikrein, Pharvaris’ program, known as PHA121, is a bradykinin B2 receptor antagonist.
Thus far, the only approved drug to treat HAE comes from BioCryst, which picked up a green light for Orladeyo back in December 2020. The drug recorded $114.9 million in sales for the first half of 2022.