KVD900 for HAE
KVD900 is an oral plasma kallikrein inhibitor and the most advanced compound in our portfolio of candidates for the treatment of hereditary angioedema (HAE), with Phase 2 clinical trial enrollment expected to complete in 2019 and data in 2020.
In mid-2018, we released data from a first-in-human Phase 1 trial, investigating the safety, tolerability and exposure to KVD900. The placebo-controlled study recruited 84 healthy volunteers and included single-ascending dose, formulation and food-effect cross-over phases. 68 subjects received KVD900 and of those, 18 received the maximum 600 mg dose. No serious adverse events (SAEs) were reported, and of the 45 adverse events (AEs), 19 were treatment emergent. All AEs were considered mild except a single AE of headache reported at the 10 mg dose. One GI AE was reported 3 days following dosing during the food-effect phase and was considered unlikely related to treatment. Maximum plasma concentrations of KVD900 were achieved around one hour following administration of the capsule formulation. The intended commercial tablet formulation was absorbed more rapidly and resulted in higher plasma concentrations than the capsules delivering 95% inhibition of plasma kallikrein within 30 minutes, with effective concentrations lasting for up to 10 hours. The food effect cohort showed that dosing after food had little impact on the pharmacodynamic profile of the drug.
We believe that the exposure profile of KVD900 is ideal for an acute oral HAE therapy. Early treatment of HAE attacks has been shown to be key in maximizing treatment efficacy. Dosing with approved injectable treatments is often delayed undermining treatment outcomes. As a result of its straightforward oral administration combined with its rapid uptake and encouraging safety profile, KVD900 has the potential to offer HAE patients an effective and convenient treatment option.
The ongoing double blind, placebo-controlled Phase 2 trial will evaluate KVD900 as an on-demand treatment for HAE attacks. The study will recruit approximately 50 type 1 and 2 HAE patients at 10-15 sites in the UK, Germany and several other European countries. During part one of this two-part study patients not having an attack will receive a single 600 mg dose of KVD900 to explore pharmacokinetic and pharmacodynamic properties. All patients will enter part two of the study, which is a randomized, two attack, crossover investigation of the efficacy of KVD900 versus placebo. Within one hour of the onset of an attack patients will take a single dose of 600 mg of KVD900 or placebo. A second attack will be dosed with the alternative crossover treatment. Patients will have access to their normal, on-demand treatment if needed. For all attacks, data will be collected for 24 hours on endpoints including symptom severity using visual analog scale (VAS) and the Likert scale, as well as patient use of their standard of care therapy.