HAE is a rare genetic disorder in which patients experience sudden onset of swelling in various locations of the body. Disease symptoms typically begin during childhood and become more pervasive during puberty and adulthood. Patients with HAE lack (type I) or have dysfunctional forms (type 2) of C1-inhibitor, a critical protein that controls the enzyme plasma kallikrein. Some number of patients, known as type 3, experience HAE attacks despite having normal levels of C1-inhibitor. In an HAE attack, lack of C1-inhibitor leads to excessive activation of plasma kallikrein that in turn generates the vasoactive peptide bradykinin, which is responsible for a sudden increase in vascular permeability and leakage of fluid into tissues. Swelling attacks can occur anywhere in the body, ranging from swelling of the abdomen which, if undetected, can lead to unnecessary surgery, to swelling of the airways, which can lead to asphyxiation and death. The disease occurs in approximately 1 in 10,000 to 1 in 50,000 people. Replacing C1-inhibitor or inhibiting activated plasma kallikrein or bradykinin has become the mainstay of therapy for HAE in the US since the early 2000s, although all the currently approved therapies are delivered by injection or infusion. An orally delivered, small molecule inhibitor of plasma kallikrein offers the opportunity to improve treatment for the disease by making it more convenient for patients to take therapies.
We reported positive Phase 2 results evaluating KVD900 as an on-demand treatment for HAE attacks in February 2021. We now intend to interact with regulators to determine the requirements for future clinical trials to support filing of a New Drug Approval (NDA). We believe there is a well-defined regulatory pathway for an oral on-demand treatment of acute HAE.
KVD824 is in development for prophylactic treatment of HAE. We expect to initiate a Phase 2 clinical trial of KVD824 in the second quarter of 2021. This trial will be intended to evaluate the efficacy and safety of KVD824 as a twice-daily prophylactic treatment for prevention of HAE attacks.