CSL Behring has announced results of a Phase 2 clinical trial for garadacimab (previously known as CSL312), an investigational novel Factor XIIa-inhibitory monoclonal antibody (FXIIa mAb) in development as a preventive treatment in HAE. The data, presented at the European Academy of Allergy and Clinical Immunology (EAACI) Digital Congress 2020, showed that the study met its primary endpoint, demonstrating reduced number of attacks compared to placebo in patients with HAE.
Mean percentage reductions were 88.68%, 98.94%, and 90.50% in three garadacimab groups – 75, 200, and 600 mg subcutaneous versus placebo. The study also showed garadacimab to be well-tolerated.
Garadacimab inhibits the plasma protein, FXIIa. FXIIa initiates the cascade of events that lead to edema formation. By targeting FXIIa, garadacimab can prevent the initiation of this cascade.
Additionally, last month, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to garadacimab as an investigational therapy for the prevention of bradykinin-mediated angioedema, which includes both hereditary and non-hereditary (acquired) angioedema. The FDA Office of Orphan Products Development (OOPD) grants orphan drug designation to novel drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 U.S. patients. The designation qualifies companies with a range of incentives, including the potential for marketing exclusivity upon approval.
“The attacks that HAE patients experience can be very frightening, and clinicians want to do anything in their power to reduce the frequency of these attacks, lessen the need for rescue medicine and simplify treatment,” says lead study investigator Timothy Craig, D.O., Allergy, Asthma and Immunology, Department of Medicine and Pediatrics, Penn State Hershey, Hershey, PA. “The findings of this study are very encouraging and we look forward to further research assessing the safety and efficacy of garadacimab.”
“Consistent with our more than 40-year commitment to HAE therapeutic innovation, garadacimab represents a potentially first-in-class agent that utilizes a unique approach as a preventive treatment in HAE,” says Mittie Doyle, M.D., Vice President, Research and Development, Immunology Therapeutic Area at CSL Behring. “We are encouraged by the promising garadacimab data as well as the orphan drug designation milestone and look forward to advancing the clinical program to continue to deliver on our promise and improve the lives of people living with HAE.”
About the Phase 2 Study
In the Phase 2 study, a total of 32 adults with HAE were randomized and received either garadacimab (either 75 mg, 200 mg or 600 mg) or placebo every four weeks for 12 weeks. Researchers observed the following:
Significantly fewer monthly attacks in all three groups taking garadacimab, with garadacimab reducing the mean attack rates by 88.68%, 98.94% and 90.50%, respectively, compared to placebo. Specifically, the monthly attack rates were 0.48, 0.05 and 0.40 for the three doses of garadacimab compared to 4.24 for placebo. As comparison, patients experienced a mean monthly attack rate of 5.17 prior to the start of the study. A large portion of patients taking garadacimab were attack-free during the course of the study. Specifically, 55.56%, 87.5% and 42.86% of patients taking garadacimab, respectively, did not have any attacks compared to zero percent in the placebo group.
All adverse events were mild or moderate, with the percentage of patients experiencing at least one treatment-emergent adverse event (TEAE) being similar across all groups. The common TEAE was mild to moderate injection site erythema (12.5%).
Additional Study Details
This multicenter, randomized, double-blind, placebo-controlled, parallel-arm Phase 2 study (NCT03712228) examined the efficacy, safety and pharmacokinetics of three different doses of garadacimab, an novel investigational FXIIa mAb, compared to placebo for the preventive treatment of HAE. Enrolled patients were 18-65 years of age with type I or type II HAE, with four or more documented attacks over a consecutive two-month period during the three months prior to screening. Patients were randomized to receive either garadacimab 75 mg, garadacimab 200 mg, garadacimab 600 mg or placebo, which were given as a subcutaneous injection every four weeks for 12 weeks after an intravenous loading dose. The primary endpoint was the number of attacks. Secondary endpoints included the reduction in attacks compared with the run-in period (4 or up to 8 weeks prior to the start of treatment) or placebo, use of on-demand therapies (to treat an attack) per month and safety.
(Source: CSL Behring)