KalVista’s HAE Treatment KVD900 Now Called Sebetralstat

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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KVD900, KalVista Pharmaceuticals’ investigational on-demand treatment for swelling attacks in people with hereditary angioedema (HAE), will now be called sebetralstat, the company announced.

Sebetralstat will become the nonproprietary nomenclature for the treatment’s active ingredients, meaning that will be the generic name for any medication using the same formulation in the future.

This proposed name was cleared by the World Health Organization’s International Nonproprietary Names (WHO-INN) Expert Committee and the American Medical Association’s United States Adopted Names (AMA-USAN) Council.

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A Phase 3 trial called KONFIDENT (NCT05259917) is evaluating sebetralstat’s safety and efficacy among adults and adolescents over age 12 with HAE types 1 and 2. To participate, patients must have experienced at least two HAE swelling attacks in the three months before enrollment.

The trial is expected to recruit 114 participants from about 60 clinical sites in 20 countries. Currently, several U.S. locations and one site in Puerto Rico are listed on the trial’s webpage.

“We are excited to announce this next important step in the evolution of sebetralstat as the first potential oral on-demand therapeutic for HAE,” Andrew Crockett, KalVista’s CEO, said in the press release.

“The KONFIDENT study continues to enroll on track with our expectations, and we have many other activities ongoing to prepare for the eventual [new drug application] submission. We believe sebetralstat can be a transformational therapy for people living with HAE,” Crockett added.

In HAE, genetic mutations lower the production or lead to the malfunction of the C1-inhibitor protein, which consequently causes an enzyme called kallikrein to become overactive. In turn, kallikrein gives rise to an excessive amount of the inflammatory molecule bradykinin, which is the cause of sudden and severe episodes of tissue swelling characteristic of the disease.

Sebetralstat is an oral therapy designed to inhibit kallikrein. It is intended to be used “on-demand,” meaning that it can be taken at the onset of a swelling attack to prevent it from worsening. Currently available on-demand treatments are delivered as injections, making sebetralstat’s oral formulation unique.

Data from previous Phase 1 trials in healthy volunteers showed the treatment quickly — and nearly entirely — suppressed kallikrein activity.

A previous Phase 2 trial (NCT04208412) demonstrated that sebetralstat slowed the progression of swelling attacks and eased symptoms sooner than a placebo in people with type 1 or type 2 HAE. The proportion of patients who required additional rescue therapies to stop swelling attacks was also lower among those given sebetralstat.

Now, participants in KONFIDENT will be randomly assigned to take one of two doses of sebetralstat (300 or 600 mg) or a placebo tablet when they become aware of a swelling attack beginning. If symptoms warrant, participants will be able to take an additional dose of sebetralstat.

The trial’s design is crossover, meaning that three HAE attacks will be evaluated for each patient, with each attack treated with a different intervention (placebo, 300 mg, or 600 mg).

Participants will also be allowed to continue any of their ongoing preventive HAE treatments and will have access to other rescue treatments that they usually use.

The trial’s main goal is to assess how long it takes for patients to begin feeling symptom relief, as measured with a Patient Global Impression of Change scale. Safety and other effectiveness measures of swelling reduction will also be assessed.