KVD900 shows promise in early trial, gives hope to hereditary angioedema patients

KVD900, and oral inhibitor of plasma kallikrein (PKa), safely and rapidly induces near-complete PKa inhibition, reports two phase I studies.

“A safe, oral, on-demand treatment for hereditary angioedema (HAE) attacks that provides fast-acting and highly effective PKa inhibition may provide HAE patients with a noninvasive alternative to rapidly halt attack progression,” the researchers said. “The phase I investigations presented here support the potential for KVD900 as a generally well-tolerated and safe oral on-demand treatment for patients with HAE.”

The first study adopted a randomized, double-blind, placebo-controlled, single-ascending dose (5–600 mg) design, followed by an open-label crossover phase. This study enrolled 84 healthy adult men.

The second study was a randomized, double-blind, placebo-controlled, multiple-dose analysis of 42 adults under fasted conditions. Participants were divided into three cohorts who were given 600 mg KVD900 at 8-, 4-, and 2-hour intervals.

In the first study, 26 adverse events (AE) were reported by 19 patients. Most side effects were mild, with only one patient reporting a moderate AE. Headache was the most common AE. There were no incidences of gastrointestinal AEs except for one case of vomiting deemed unrelated to KVD900. In the second study, 19 AEs were documented, all of which were mild and had resolved by the end of the study.

In terms of pharmacokinetics, the 600-mg tablet form of KVD900 reached a mean maximum plasma concentration of 6,460 ng/mL after a median time of 0.5 hours. Meanwhile, its mean area under the curve was 18,600 h·ng/mL.

Additionally, KVD900 achieved a >98-percent mean PKa inhibition between 20 minutes and 3 hours, suggesting near-complete inhibition. Notably >90-percent inhibition of PKa was successfully maintained for ≥8 hours after administration.