KVD824 for hereditary angioedema

Last updated April 17, 2024, by Margarida Maia, PhD
Fact-checked by Joana Carvalho, PhD

What is KVD824 for hereditary angioedema?

KVD824 is an investigational oral small molecule that was being developed by KalVista Pharmaceuticals as a preventive treatment for people with hereditary angioedema (HAE). The company decided to terminate a Phase 2 clinical trial of the therapy early for safety reasons, and it does not anticipate any further testing of KVD824.

Therapy snapshot

How does KVD824 work in hereditary angioedema?

Angioedema refers to swelling that occurs in tissues in the deeper layers of the skin. In HAE, this is generally due to genetic mutations that cause the loss or malfunctioning of a protein called C1-inhibitor. Without C1-inhibitor, an enzyme called kallikrein becomes overactive and triggers the excessive release of bradykinin. High levels of bradykinin cause blood vessels to widen and leak fluid into tissues, resulting in swelling.

KVD824 is a small molecule designed to inhibit the activity of kallikrein in the blood. It was expected to prevent or ease HAE swelling attacks.

How was KVD824 administered in hereditary angioedema?

In a clinical trial involving HAE patients, KVD824 was given in the form of modified-release tablets containing 300, 600, or 900 mg of therapy’s active ingredient. Participants took the tablets twice daily for 12 weeks, or about three months.

KVD824 in hereditary angioedema clinical trials

KVD824 has been tested in both healthy volunteers and people with HAE. However, its clinical development was stopped in 2022 due to safety concerns.

Phase 1 trials

A Phase 1 clinical trial (NCT05178355) tested the safety and tolerability of KVD824, at single doses up to 1,280 mg and multiple doses up to 640 mg, against a placebo tablet in 84 healthy men, ages 18 to 55. It also tested the effects of food on the pharmacokinetics of KVD824, which assesses how a drug moves into, through, and out of the body. KVD824 was found to be safe and well tolerated when given as immediate-release capsules once or twice daily for up to five days, with no serious side effects reported.

The first part of another Phase 1 clinical trial (NCT05118958) compared the pharmacokinetics of KVD824 as modified-release tablets against immediate-release capsules in 16 healthy men and women, ages 18 to 55. KVD824 was given as modified-release tablets at a single dose of 600 or 900 mg either with food or in a fasting state, or as immediate-release capsules at a single dose of 600 mg in a fasting state.

Building on findings in the study’s first part, 27 healthy volunteers then were randomly assigned to modified-release tablets of KVD824 at 600 or 900 mg, taken with a standard meal or while fasting, or to a placebo tablet. Twice-daily dosing of KVD824 for 14 days resulted in steady levels of the medication in the blood, with both the 600 mg and the 900 mg doses maintaining levels above those required to be effective.

Side effects reported to be related to KVD824 were mild. The most common were headache, frequent urination, and nose bleeds. Side effects thought to be possibly related to KVD824 included joint stiffness, joint swelling, muscle spams, itching, and elevated levels of liver enzymes, a potential sign of liver damage. No study participant stopped treatment with KVD824 due to side effects.

KOMPLETE Phase 2 trial

A Phase 2 clinical trial called KOMPLETE (NCT05055258) aimed to assess the efficacy of KVD824 in preventing swelling attacks in 33 adults with HAE type 1 or 2; all had at least three attacks during eight weeks (about two months) of a run-in study period.

Patients were randomly assigned to modified-release tablets of KVD824 at a 300, 600, or 900 mg dose or to a placebo, taken twice daily for 12 weeks. However, after seven patients using KVD824 showed moderate-to-severe or severe elevations in liver enzymes between the second and 12th week of treatment, the company decided in October 2022 to stop the trial.

Common side effects of KVD824

The most common side effect associated with KVD824’s use in people with HAE was elevated levels of liver enzymes.

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