KalVista Pharmaceuticals plans to initiate a Phase 3 trial for KVD900, a treatment for hereditary angioedema (HAE) after finding positive results from earlier Phase 1 and 2 trials. The Phase 1 data has been published in the Journal of Allergy and Clinical Immunology, while the Phase 2 trial just recently finished. Both studies discovered that KVD900 suppresses kallikrein while maintaining a positive safety profile and being well-tolerated in healthy participants.

About the Studies

Kallikrein is a driving mechanism behind the inflammation that characterizes HAE. KVD900’s purpose is to block this enzyme’s action, therefore lowering the number of HAE attacks or even preventing them entirely. It is an orally administered small molecule.

Phase 1 Trial

This trial enrolled 84 healthy adult participants in an effort to evaluate KVD900’s pharmacological properties, safety, and tolerability. 64 of these participants were given single-ascending doses (SAD) of KVD900, starting at 5 mg and ending at 600 mg, or a placebo.

Results from this trial include:

• Cmax (the maximum concentration of the drug in the bloodstream) was achieved within the hour
  • It also increased with each dose
• KVD900’s half-life is 1.94 to 11.7 hours across the various dosages that were tested
• Increasing doses led to kallikrein activity being reduced by 90%
• Adverse effects (AEs) were mild and not typically related to treatment
  • One headache was reported at a 10 mg dose, but researchers are unsure as to if this is the result of KVD900
  • Mild dizziness was experienced by one participant at the 10 mg dose as well

Separate experiments were also performed within this trial in order to gain the best understanding of the drug. One focused on the best formulation of the drug, capsule or tablet. Four participants were given 100 mg of KVD900 in a capsule and four in a tablet, and then the two groups switched one week afterward. The researchers found that the tablet was the superior formulation, as it increased Cmax by 53% while being absorbed at a faster rate without impacting the half-life.

The next experiment focused on food consumption and its impact on KVD900. Two groups of six volunteers were given 600 mg of the drug, one before a meal and the other after. After 48 hours, the two groups switched and performed the experiment again. Overall, eating food did not impact exposure; however, eating right before taking the medication was found to slow absorption.

In the end, the Phase 1 trial found that KVD900 was safe and well-tolerated in healthy adult participants.

Phase 2 Trial

The second phase in this series confirmed what the first phase discovered. 68 adult participants, all diagnosed with HAE and experiencing at least three swelling attacks in the prior three months, were enrolled. Not only was the safety profile confirmed, but symptom resolution occurred faster and swelling attacks were reduced or prevented entirely.

Looking Forward

Now that Phase 1 and 2 trials are completed, KalVista plans to move forward with a Phase 3 trial. 100 HAE patients are planned to enroll across 50 sites, with dosing expected to begin later this year. Hopefully, this drug continues to produce positive results in trials, as it could provide meaningful benefits for HAE patients.

About HAE

A genetic defect on Chromosome 11 causes hereditary angioedema (HAE), a rare disorder characterized by episodes of swelling under the skin. This defect is passed down in an autosomal dominant pattern. Affected individuals have a protein that does not function properly, C1-inhibitor. When this protein does not do its job, excessive amounts of bradykinin are produced. It is this peptide that causes the characteristic swelling of HAE.

This swelling occurs in the form of episodes, and it can affect any part of the body. However, it most commonly impacts the throat, face, intestinal tract, and extremities. Intestinal symptoms may also include nausea, vomiting, and pain, alongside swelling. If the throat swells it’s important to seek help, as it could stop the affected individual from breathing.

Find the source article here.