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KalVista Terminates of KVD824 Phase 2 Trial for Prophylactic Treatment of Hereditary Angioedema

October 5, 2022

KalVista Pharmaceuticals said that it has terminated the KOMPLETE phase 2 clinical trial for KVD824 for the prevention of attacks in people with hereditary angioedema (HAE) after observing elevation of a liver enzyme in multiple patients in all treatment groups of the trial.

Photo: Andrew Crockett, CEO of KalVista

No patients had concomitant elevation of bilirubin levels, and all were asymptomatic.

“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 Andrew Crockett, CEO of KalVista. “This termination conserves our financial resources and allows us to focus on continuing to advance sebetralstat through the ongoing phase 3 program and towards a planned 2024 NDA filing, as well as on our emerging oral factor XIIa inhibitor program as a potential once daily prophylactic therapy for people with HAE.”

Hereditary angioedema (HAE) is a rare genetic disorder that results in recurring attacks of edema, or swelling, in various parts of the body, including the abdomen, face, feet, genitals, hands and throat. The swelling can be debilitating and painful. Attacks that obstruct the airways can cause asphyxiation and are potentially life threatening.

HAE attacks may occur early in childhood. Potentially fatal upper airway angioedema has been reported in patients as young as 3 years old. HAE diagnosis can take an average of 8.4 years after symptom onset. HAE affects an estimated 1 in 50,000 people worldwide and is often under recognized, under diagnosed, and under treated. There are currently no long-term prophylactic treatments approved for HAE patients younger than 6 years.

The KOMPLETE trial is a phase 2 clinical trial evaluating KVD824, an investigational oral plasma kallikrein inhibitor designed for the prevention of attacks in adults living with HAE. Patients in the trial were randomized to one of three treatment groups, each placebo controlled: 300 mg, 600 mg, 900 mg KVD824 (or placebo), all dosed twice daily. A total of 33 patients were enrolled in the trial, of which 7 patients experienced either Grade 3 or Grade 4 elevations of liver enzymes at timeframes ranging from two to twelve weeks. The elevations were noted in all treatment groups. One additional Grade 4 elevation was recorded in a patient at the baseline visit, prior to receiving study drug. KalVista will proceed to finalize the database of the trial and assess the unblinded data for efficacy and safety to determine the potential for any further development.

KalVista is developing sebetralstat as an oral on-demand therapy for HAE attacks and is enrolling the phase 3 KONFIDENT clinical trial. The company continues to recruit the phase 3 KONFIDENT trial assessing sebetralstat as a potential oral, on-demand therapy for HAE attacks, with data anticipated in the second half of 2023. Sebetralstat is a distinct compound from KVD824, and no treatment related liver enzyme elevations in patients have been observed in any sebetralstat clinical studies, including in the ongoing phase 3 KONFIDENT trial.

Author: Rare Daily Staff

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