A phase 2 clinical trial known as KOMPLETE, testing the investigational hereditary angioedema (HAE) treatment KVD824, has been terminated, according to KalVista Pharmaceuticals, the developers of the treatment. This is because of an increase in liver enzymes (ALT/AST) in many patients receiving the treatment.
“The health and safety of participants in our clinical trials is of utmost importance to us,” said Andrew Crockett, the chief executive officer of KalVista. “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.”
The phase 2 trial was testing the safety and efficacy of 3 doses of KVD824 (300, 600, and 900 mg twice a day) for the prophylactic treatment of HAE attacks.
Thirty-three patients were enrolled in the trial. Of these, 7 had grade 3 or 4 elevations in liver enzymes 2 to 13 weeks after starting treatment. The increases were seen in patients being treated with all 3 doses of KVD824. All patients were asymptomatic and none had concomitant elevations in bilirubin.
Read more about KVD824 and other experimental treatments for hereditary angioedema
The company will now focus its attention on developing another potential HAE treatment, known as sebetralstat.
KVD824 is an oral plasma kallikrein inhibitor. It was designed to prevent HAE attacks by blocking the release of bradykinin from bound high-molecular-weight kininogen. Bradykinin binds to bradykinin B2 receptors on the vascular endothelium, promoting vasodilation and transfer of fluid into the tissues. In HAE, a mutation in the SERPING1 gene results in deficient or absent C1-INH, the role of which is to regulate the kallikrein-kinin pathway.
KalVista Pharmaceuticals announces termination of KVD824 phase 2 KOMPLETE trial for prophylactic treatment of hereditary angioedema. News release. KalVista Pharmaceuticals; October 4, 2022.
A trial to evaluate the efficacy and safety of different doses of KVD824 for prophylactic treatment of HAE type I or II (KVD824-201). US National Library of Medicine. Last updated September 19, 2022. Accessed October 6, 2022.