Phase 2 Trial Planned for Investigational HAE Therapy KVD900 After Positive Phase 1 Results

KalVista Pharmaceuticals’ investigational candidate KVD900, being developed for the treatment of hereditary angioedema (HAE), is safe and effectively inhibits kallikrein, the main driver of HAE attacks, results from a Phase 1 clinical trial show.

Following these positive results, the company is now launching a larger Phase 2 trial to evaluate KVD900 as an on-demand treatment for HAE attacks. The trial is expected to begin before the end of the year, and investigators hope it will lead to accelerated approval by the U.S. Food and Drug Administration.

“Thanks to our recent equity financing and the exciting Phase 1 data from KVD900, we are pleased to announce that we are building on these successes with a more aggressive development plan for KVD900, to potentially accelerate our time to market,” Andrew Crockett, CEO of KalVista, said in a press release.

HAE patients have a defect in the gene that provides instructions for making an inhibitor of kallikrein, resulting in uncontrolled plasma kallikrein activity and elevated levels of the inflammatory mediator bradykinin. Ultimately, bradykinin causes vessels to dilate and to become more permeable, leading to tissue swelling (edema).

KalVista is developing small molecule inhibitors of the plasma enzyme kallikrein, including KVD900 and KVD818, which has also completed a Phase 1 study.

The Phase 1 trial of KVD900 enrolled 68 healthy volunteers who received increasing doses of oral KVD900 to determine its safety, tolerability, and behavior inside the body.

The therapy was well-tolerated, even among the 18 participants receiving the highest dose, and showed an acceptable safety profile. Additionally, dosing after a meal — including meals high in calories or fats — had no impact on the effectiveness of KVD900, which continued to inhibit kallikrein by 95% within 30 minutes.

The findings suggest that KVD900 compares favorably with currently available injectable therapies, and could be suitable for use as an on-demand therapy for HAE attacks.

The upcoming Phase 2 trial will now test the treatment in a large population of HAE patients — including those with type 1 and type 2 HAE — and will be conducted in two parts. First, patients will receive KVD900 in an in-patient setting, where they will be monitored for safety and drug metabolism.

Then patients will cross over to an out-patient setting, where they will receive KVD900 or a placebo within one hour of the start of an attack. Symptoms will be monitored for at least 24 hours after treatment administration. Patients will be allowed to use their normal, on-demand treatment if the attacks worsen.

The study will include 50 patients and is expected to conclude by late 2019.