Phase 3 Study of Oral KVD900 as On-Demand Therapy Likely in 2022

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by Steve Bryson, PhD |

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KalVista Pharmaceuticals is planning to launch a Phase 3 trial of KVD900, an investigational oral and on-demand treatment for adults with hereditary angioedema (HAE), with dosing expected to begin in early 2022.

“Our development team is finalizing the Phase 3 trial protocol and preparing for study initiation, and we anticipate patients will be dosed during the first quarter of 2022,” Andrew Crockett, CEO of KalVista, said in a press release.

KVD900 is designed to block the activity of the enzyme kallikrein, which is overactive in HAE due to the lack of the C1-inhibitor (C1-INH) protein. A low level of C1-INH in the bloodstream is characteristic of type 1 HAE, whereas problems with how C1-INH works is the underlying cause of type 2 HAE.

By lowering kallikrein’s activity and the production of bradykinin — a pro-inflammatory molecule that promotes swelling — KVD900 is expected to reduce or prevent swelling attacks that are characteristic of HAE.

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KalVista recently completed a Phase 2 trial (NCT04208412) at sites in the U.S., the U.K., and Europe that enrolled 68 adults with type 1 or type 2 HAE who had more than three swelling attacks in the three months before entering the trial.

According to the study’s latest data, the oral medication safely slowed the progression of swelling attacks and reduced the time to symptom relief and resolution.

Based on these findings, the company engaged with the U.S. Food and Drug Administration (FDA) to determine the requirements of advancing KVD900 into Phase 3 testing, which is expected to support the filing of a new drug application (NDA) seeking the therapy’s approval.

“We had a productive End-of-Phase 2 meeting with the FDA and recently received meeting minutes which confirmed that our Phase 3 trial design, similar to our recent successful Phase 2 trial, is expected to be appropriate to support an NDA submission,” Crockett said.

Like the Phase 2 study, the Phase 3 trial will have a crossover design. Two doses of KVD900 (300 and 600 mg) will be tested against a placebo. Participants will be instructed to administer treatment as soon as they recognize an attack’s onset.

The study’s primary goal will be to determine the time to the beginning of symptom relief.

The study is expected to enroll about 100 patients at more than 50 sites worldwide. It will evaluate the therapy’s ability to reduce all HAE attacks, including laryngeal attacks, as well as breakthrough attacks for patients using preventive, or prophylactic, treatments.

KalVista is also developing KVD824, a similar kallikrein inhibitor intended to prevent swelling attacks in HAE patients.

The company’s plan to launch the Phase 2 KOMPLETE study (NCT05055258) to evaluate KVD824 as a prophylactic therapy in HAE patients was temporarily put on hold by the FDA, which requested further preclinical data and changes to the trial’s protocol.

KalVista responded and the FDA lifted its hold in September. KOMPLETE is now enrolling up to 48 adult patients at locations across the U.S., Canada, and Puerto Rico; information is available here. Additional sites in the U.S., U.K., Australia, Canada, New Zealand, Czech Republic, Germany, and Hungary are expected to open soon.

“KalVista is well-capitalized, with funding until at least early 2024, which we expect takes us beyond data from both this Phase 3 trial and the ongoing Phase 2 trial of KVD824,” said Crockett.