What is HAE?
HAE is a rare genetic disease characterized by a sudden onset of swelling in various locations of the body. The first symptoms usually appear in childhood and become more severe in puberty and adulthood.
Enzymes called kallikreins control blood pressure by regulating how much bradykinin, a peptide that controls inflammation, is active at any time. When kallikreins are active, more bradykinin is available, which in turn causes an increase in the permeability of blood vessels and fluid leakage into tissues. A protein called a C1-inhibitor tightly controls kallikrein activity.
Patients with HAE either lack C1-inhibitors (type 1 HAE) or have dysfunctional C1-inhibitors (type 2 HAE). During an HAE attack, kallikrein activity increases, resulting in the overactivation of bradykinin and swelling in various parts of the body.
The most common therapies for HAE focus either on replacing C1-inhibitors or inhibiting plasma kallikrein or bradykinin. Available treatments must be infused or injected.
How does KVD900 work?
KVD900 is a small-molecule inhibitor of plasma kallikrein. It binds to kallikrein and prevents it from activating bradykinin. This reduces the permeability of the blood vessels and fluid leakage into tissues, thereby potentially reducing or even preventing swelling.
KVD900 in clinical trials
In a Phase 1 clinical trial (NCT04349800), 84 healthy volunteers received single ascending doses of KVD900. Results demonstrated that participants tolerated doses as high as 600 mg. The concentrations of the treatment in the blood increased rapidly after dosing, reaching what KalVista considers “effective concentrations” within 30 minutes. Pharmacodynamics, or how the treatment affected the body, demonstrated that KVD900 inhibits kallikrein from causing bradykinin release for up to 10 hours following a single dose.
An ongoing Phase 2 trial (NCT04208412) recruited 68 patients with type 1 and type 2 HAE at sites in the U.S., the U.K., and Europe to test the safety and efficacy of KVD900 compared with a placebo. During the trial, patients randomly receive KVD900 or a placebo following an HAE attack. The primary outcome measure is the amount of time it takes until patients need a traditional HAE treatment. The study is also measuring how many HAE attacks progress by one or more levels on the five-point Likert scale and how long it takes for these to progress.
Researchers estimate the trial will be completed by the end of 2020. At that point, KalVista plans to consult with regulators and determine future clinical trial requirements to support filing a new drug application for the treatment to the U.S. Food and Drug Administration.
Last updated: Nov. 23, 2020
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