In conjunction with the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting 2019 in San Francisco, CA. KalVista Pharmaceuticals, Inc. CEO Andrew Crockett said:
“We are pleased to provide additional data on KVD900, showcasing a potentially ideal profile for oral on-demand treatment of HAE. Both formulations tested were rapidly and highly absorbed, driving a very fast onset of plasma kallikrein inhibition. The tablet formulation we plan to use commercially showed even faster uptake, with high levels of plasma kallikrein inhibition maintained for a long period and KVD900 was generally safe and well tolerated. Our Phase 2 study of KVD900 in HAE patients is expected to provide data late this year.”
KVD900 was evaluated in a randomized, double-blind, placebo-controlled Phase 1 single ascending dose study. 64 healthy male participants (n=6 active, 2 placebo per cohort, 8 cohorts) were administered single doses of KVD900 5, 10, 20, 40, 80, 160, 300 or 600 mg in a capsule. 8 participants were administered 100 mg KVD900 in a crossover study of the capsule and a tablet formulation. 12 participants were administered 600 mg KVD900 in a food effect crossover study.
- Orally administered KVD900 achieved rapid and dose-dependent plasma exposure over the range of doses tested from 5 mg to 600 mg
- A single 600 mg dose provided >90% plasma kallikrein inhibition and protection of high molecular weight kininogen (HK) cleavage from dextran sulphate-stimulated cleavage shown by capillary-based immunoassay. HK cleavage is the process by which plasma kallikrein is released during the inflammatory cascade that causes HAE attacks.
- The pharmacodynamic effects of KVD900 inhibition of HK cleavage was maintained for over 10 hours at the 600 mg dose level
- All doses of KVD900 over 80 mg provided complete inhibition of plasma kallikrein