KalVista Pharmaceuticals, Inc. presents data for its oral on-demand plasma kallikrein (PKa) inhibitor and Factor XIIa (FXIIa) programs at the EAACI2022 conference in Prague, Czech Republic.
Data shows that sebetralstat was an effective treatment for both peripheral and abdominal attacks with 80% of attacks achieving symptom relief within 12 hours, regardless of attack location. Population pharmacokinetic (PK) data showed that the PK of sebetralstat did not appear to be affected by consumption of a normal meal prior to dosing compared with taking the dose after fasting. Furthermore, PK modeling supports the use of sebetralstat in adolescents 12 years and older without dose adjustment.
Animal model data with oral FXIIa inhibitor KV998086 showed the compound protected mice from kallikrein-kinin system (KKS) mediated edema. KV998086 blocked the generation of FXIIa & PKa and prevented HK cleavage in a dose-responsive manner. Pharmacokinetic studies showed that oral KV998086 displayed high bioavailability. Inhibition of the KKS with KV998086 may provide an opportunity for once-daily HAE prophylaxis as well as having the potential to treat other KKS-mediated diseases.
“The population PK study is important for our sebetralstat program,” says Andrew Crockett, CEO of KalVista. “It expands the population we can target for treatment in our Phase 3 KONFIDENT trial without having to use multiple-dose regimens. Additionally, the preclinical data with our oral FXIIa inhibitor once again shows the promise of this novel class of compounds, which will be important to our company’s future even beyond HAE.”