Mission in-Komplete: KalVista axes angioedema program over raised enzyme levels

KalVista Pharmaceuticals' share price has been cut in half after the company scrapped one of its hereditary angioedema programs in the face of multiple reports of raised enzyme levels.

Elevated ALT and AST levels were observed in seven patients spread across all three dose cohorts that were being tested in the phase 2 KOMPLETE trial, the company said in a press release. The placebo-controlled study had enrolled 33 patients and was evaluating 300 mg, 600 mg or 900 mg twice-daily doses of KVD824.

While all seven patients with raised enzyme levels were asymptomatic, KalVista nonetheless decided to nix further development of KVD824. “We made the difficult decision to terminate KOMPLETE because we concluded that the emerging safety profile of the current formulation will not meet our requirements for a best-in-class oral prophylactic therapy,” said KalVista CEO Andrew Crockett in an premarket release Oct. 4.

KVD824, a plasma kallikrein inhibitor, was being developed as a preventative treatment for HAE attacks.

The drug has not had a smooth journey to phase 2 trials. Last year, it was slapped with a clinical hold from the FDA, as the agency demanded more preclinical data and changes to its protocol.

Terminating the program will help conserve the biotech’s financial resources as it pivots its focus to advancing sebetralstat—another plasma kallikrein inhibitor being developed as an on-demand therapy for HAE attacks—through phase 3 and towards a planned filing for approval in 2024, Crockett said in the press release. The U.K.-U.S. biotech continues to recruit patients to this trial, none of whom have shown treatment-related enzyme level rises, according to the release.

HAE results in recurrent attacks of severe swelling, most commonly of the arms, legs, face, intestinal tract and airway. KalVista has another prophylactic HAE treatment in the works in the form of a preclinical oral factor XIIa inhibitor.

Apart from HAE, the company’s other clinical-stage asset is a diabetic macular edema drug called KVD001, which has completed phase 2 trials.

KalVista’s shares were down about 52% to $6.70 apiece when the markets opened today (Tuesday).