Enrollment Completed in Phase 2 Trial of Oral On-demand HAE Therapy KVD900

The Phase 2 clinical trial testing KalVista Pharmaceuticals‘ oral investigational therapy KVD900 as an on-demand treatment for hereditary angioedema (HAE) attacks has completed enrollment, the company announced. Results from the trial are expected by year’s end.

Meanwhile, the company has submitted a pediatric investigational plan for KVD900 to the European Medicines Agency. This is a necessary step to initiate studies meant to support a future marketing approval in children.

“We believe KVD900 can bring the first effective and well-tolerated oral on-demand treatment option to patients suffering from hereditary angioedema attacks,” Andrew Crockett, CEO of KalVista, said in a press release.

KVD900 is a small molecule inhibitor of kallikrein, an enzyme that is continuously produced in angioedema patients lacking a functional C1-inhibitor (C1-INH) protein. The high levels of kallikrein increase the levels of the inflammatory mediator bradykinin, causing blood vessels to dilate and tissue to swell.

By inhibiting kallikrein, KVD900 is designed to lower bradykinin levels, thereby reducing the chances of an HAE attack. Notably, KVD900 is an oral therapy, addressing a highly unmet need in this patient population.

In a prior Phase 1 trial (NCT04349800), KVD900 was deemed well-tolerated in a group of healthy volunteers, and successfully inhibited the activity of plasma kallikrein within 10 minutes of being taken.

At the highest dose tested, kallikrein activity was nearly completely (by 95%) blocked after 20 minutes, and the effects lasted for up to 10 hours after the initial dosing.

The ongoing Phase 2 trial (NCT04208412) is testing KVD900 as an on-demand treatment in about 50 HAE patients — including those with type 1 and type 2 HAE — who are experiencing swelling attacks.

First, the treatment is given in an inpatient setting, where patients will be monitored for safety and drug metabolism. Patients then cross over to an outpatient setting, where they will be given KVD900 or a placebo within one hour of the start of an attack.

Patients will be monitored for symptoms for at least 24 hours after treatment administration. They will be allowed to use their normal, on-demand treatment in case the attacks worsen.

KalVista is also developing KVD824 as an oral prophylactic therapy for HAE. The therapy also inhibits the kallikrein protein, but rather than treating attacks after they happen, it is designed to prevent such attacks from occurring.

Preliminary data from a Phase 1 study testing ascending doses and repeat dosing of KVD824 showed it was well-tolerated with no signs of toxicity.

A Phase 2 trial of KVD824 is scheduled for later this year, which will assess the therapy’s pharmacokinetic and pharmacodynamic profile. Of note, pharmacokinetics refers to the movement of a drug into, through, and out of the body, while pharmacodynamics assesses the effects of a drug on the body. 

“We look forward to providing additional pharmacokinetic and pharmacodynamic data for KVD824 later this year in advance of starting a Phase 2 clinical trial,” Crockett said. “Similar to KVD900, our goal with KVD824 is to conduct a robust Phase 2 trial to provide proof-of-concept and potentially an expedited development pathway. We will provide further details on our plans as we prepare to initiate the trial.”