The agency is requesting additional information and analysis of preclinical studies regarding KVD824 before giving the go-ahead to the Phase II trial.
The U.S. Food and Drug Administration (FDA) has placed a clinical hold on KalVista Pharmaceuticals’ proposed Phase II trial of KVD824, a prophylactic treatment of hereditary angioedema. The agency is requesting additional information and analysis of preclinical studies regarding KVD824 before giving the go-ahead to the Phase II trial.
In a letter sent to KalVista, the FDA adds that the clinical-stage pharmaceutical company needs to refine the study’s protocol, but the specifics regarding these refinements have not been made publicly available. The agency has not requested any new preclinical studies, nor has it said that recent data are needed before the phase two trial can be launched.
“We intend to fully comply with the requests and recommendations provided by the FDA,” said KalVista’s Chief Executive Officer, Andrew Crockett, in a statement. “Although we no longer can confirm that the KVD824 Phase 2 trial will initiate this quarter, we are working to resolve their concerns in a timely fashion. Importantly, this letter relates solely to KVD824 and does not impact our activities or expectations with regard to KVD900, for which we continue to prepare for an End of Phase 2 FDA meeting and commencement of our Phase 3 efficacy trial.”
First-in-human and formulation studies of KVD824 conducted in the UK show the candidate features a similar safety profile as placebo. These studies have enrolled 121 people, all of whom received single doses of KVD824 up to 1280 mg, in addition to 14 days of twice-daily dosing of 600 mg and 900 mg.
The rates of adverse events in these studies were similar to that seen in the placebo and active treatment groups. None of the patients in these studies discontinued treatment, and the investigators observed no serious adverse events in either arm.
Earlier this year, KalVista announced the pricing of an upsized underwritten public offering culminating in 5,375,00 shares of the company’s common stock at a public price of $36 per share. In total, the company expected the gross proceeds from the offering to reach up to one $193.5 million. In a statement on the public offering, the company said it planned to harness the net proceeds to fund the Phase II trial of KVD824.
In addition, KalVista said it planned to use the net proceeds from the offering to finance a Phase III trial of KVD900, an oral plasma kallikrein inhibitor for the treatment of hereditary angioedema. This drug candidate previously received Fast Track designation from the FDA and a Pediatric Investigational Plan (PIP) approval from the European Medicines Agency (EMA).
In February, a Phase II trial showed KalVista’s KVD900 significantly reduced the need for rescue medication in patients experiencing hereditary angioedema attacks. This benefit was maintained for up to 24 hours. Additionally, treatment with KVD900 in patients with hereditary angioedema significantly reduced the time it took to experience relief from symptoms compared with placebo. The patients did not report any serious adverse events during the trial.
“The rapid onset of symptom relief and a significant reduction in the use of rescue medication show that patients can confidently take KVD900 at the earliest signs of an attack and avoid the burden and discomfort of injections,” said Crockett, in a statement. “We look forward to working with regulatory agencies to bring the many advantages of KVD900 to patients as quickly as possible. In parallel, we remain committed to advancing our oral HAE franchise, with submission of an IND this quarter for KVD824 as a prophylactic treatment and ongoing preclinical work on our oral Factor XIIa program.”
