UPDATED: Five months after getting slapped with a clinical hold, KalVista gets the OK to restart oral HAE program
KalVista’s oral program for the prevention of hereditary angioedema (HAE) was only on hold for five months — but that was enough time for rival Pharvaris to close in with its own on-demand and prophylactic treatment. Now that KalVista has the FDA’s permission to continue dosing patients, it’s sprinting to take the lead in Phase II.
The FDA lifted a clinical hold on KalVista’s KVD824 program after reviewing the company’s responses to a request for more information and analysis related to certain preclinical trials, the company announced early Tuesday morning. The news sent the trans-Atlantic biotech’s stock $KALV up 6.25% in premarket trading.
KalVista conducted Phase I trials for KVD824 in the UK, so the Phase II, KOMPLETE, will be the candidate’s IND-opening study in the US, CEO Andrew Crockett told Endpoints News. In addition to requesting more information from preclinical trials, the FDA called for “relatively straightforward modifications” to the Phase II protocol.
While it’s unclear what those changes were, Crockett said they did not impact “anything, I’ll say, really significant regarding the design of the study, the doses of the study, the endpoints of the study.”
“They didn’t ask us for any new data or any new study to be conducted,” he added.
HAE is a rare genetic disorder characterized by recurrent attacks of severe swelling of the skin and mucous membrane. In Phase I studies, KVD824 was shown to maintain plasma concentrations that are believed to deliver efficacy consistent with approved injectable therapies, according to KalVista. No serious side effects were reported.
KOMPLETE, the Phase II, will enroll 48 patients in 13 countries. Researchers will test 300 mg, 600 mg, and 900 mg doses against a placebo for 12 weeks, the primary endpoint is the rate of confirmed HAE attacks over the treatment period. Last week, KalVista got the green light from Canada, Australia and the UK.
“Progress continues worldwide, with regulatory submissions complete in all of the countries where the trial will be conducted,” Crockett said in a statement.
As SVB Leerink analyst Joseph Schwartz noted in a message to investors on Tuesday, it’s going to be a tight race between KalVista and Pharvaris, which reported back in July that its oral candidate for the treatment of HAE, PHA121, was well-tolerated up to the highest dose in Phase I. PHVS416, a softgel capsule formulation containing PHA121, is in Phase II for the on-demand treatment of HAE.
KalVista’s focus is on plasma kallikrein, which is upstream of Pharvaris’ target, bradykinin, Crockett explained.
“KALV’s main competitor, Pharvaris (PHVS, OP), continues to make progress with its HAE franchise centered around PHA121, as the company expects to initiate a Ph.2 prophylactic study this year (LINK). While KALV has the head start in beginning a Ph.2 prophylactic trial, PHVS is closing in, and it remains to be seen which could be first to market,” Schwartz wrote.
BioCryst’s oral drug Orladeyo was approved to prevent HAE attacks back in December, and the company announced it would charge $485,000 for it. BioCryst sought to carve out a niche as an oral option, as opposed to the injectables that have dominated the market. But the drug only reduced the number of painful incidences by 44% compared to placebo in a 96-person Phase III trial. Takeda’s injectable Takhzyro, for example, showed an 87% reduction in painful events. In July, BioCryst reported long-term data showing that those who received 150 mg doses of Orladeyo had an 80% average reduction in their mean attack rate per month during weeks 25 through 96 of the trial, compared to baseline.