KVD900 is an experimental oral treatment for hereditary angioedema (HAE) being developed by KalVista Pharmaceuticals.

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 kallikrein are active, more bradykinin is available, which in turn causes an increase in the permeability of blood vessels and fluid leakage into tissues. Kallikrein activity is tightly controlled by a protein called a C1-inhibitor. 

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. The molecule binds to kallikrein and prevents it from activating bradykinin, reducing the permeability of the blood vessels and fluid leakage into tissues — and hopefully reducing or even preventing swelling.

KVD900 in clinical trials

In a Phase 1 clinical trial, healthy volunteers received single ascending doses of KVD900. Results demonstrated that doses as high as 600 mg were well tolerated. 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) is currently recruiting 50 type 1 and type 2 HAE patients in the U.S., the U.K., and Europe to test the safety and efficacy of KVD900 compared with placebo.  Patients are randomly assigned to receive KVD900 or a placebo following an HAE attack. The primary outcome measure is the amount of time it takes until a traditional HAE treatment is required.

Results from the trial are expected in August 2020, at which point KalVista plans to consult with regulators and determine future clinical trial requirements to support filing a new drug application to the U.S. Food and Drug Administration.

 

Last updated: Jan. 17, 2020

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Angioedema News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.
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Emily holds a Ph.D. in Biochemistry from the University of Iowa and is currently a postdoctoral scholar at the University of Wisconsin-Madison. She graduated with a Masters in Chemistry from the Georgia Institute of Technology and holds a Bachelors in Biology and Chemistry from the University of Central Arkansas. Emily is passionate about science communication, and, in her free time, writes and illustrates children’s stories.
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