Garadacimab Reduces HAE Attacks Significantly, Preliminary Phase 2 Trial Results Show

Preliminary results from a Phase 2 clinical trial testing the investigational therapy garadacimab for the treatment of hereditary angioedema (HAE) show a more than 88% reduction in the number of attacks, the therapy’s developer CSL Behring announced. 

The results, presented at the European Academy of Allergy and Clinical Immunology (EAACI) Digital Congress 2020, also showed garadacimab was well-tolerated. 

Garadacimab (previously known as CSL312) is a Factor XIIa-inhibitory antibody that blocks the action of FXIIa, a protein present in the bloodstream that, once activated, starts a cascade of events that cause edema (swelling).

“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,” Mittie Doyle, MD, vice president, research and development, immunology therapeutic area at CSL Behring, said in a press release. 

An ongoing double-blind, Phase 2 trial (NCT03712228) is evaluating the efficacy, safety, and pharmacokinetics (the way a compound moves through the body) of three different doses of garadacimab compared to a placebo.

The trial has enrolled 32 patients with HAE type 1 or 2, ages 18–65, who had four or more attacks over a consecutive two-month period during the three months prior to screening.

Participants in the trial were assigned randomly to receive either garadacimab at a 75 mg dose (nine patients), a 200 mg dose (eight patients), a 600 mg dose (seven patients), or a placebo (eight patients), given as an under-the-skin injection every four weeks, for 12 weeks, after an initial dose given into the vein (intravenous loading dose). 

The study’s primary endpoint (goal) is a reduction in the number of attacks over a 13-week period.

Preliminary data showed that the trial met its primary goal, with garadacimab treatment reducing the mean number of attacks by 88.68% in patients receiving the therapy at a 75 mg dose, by 98.94% in those receiving 200 mg, and by 90.50% in people receiving 600 mg, compared to placebo.

Secondary endpoints of the study include the reduction in attacks compared with the run-in period (four or up to eight weeks prior to treatment start), or placebo, the use of on-demand therapies to treat an attack, and safety.

Results showed that the mean monthly attack rate decreased from 5.17 before the study start, to 0.48 in the garadacimab 75 mg dose group, 0.05 in the 200 mg dose group, and 0.40 in the 600 mg dose group. In the placebo group, the mean monthly attack rate was 4.24.

No attacks were recorded during the study in 55.56% of patients in the 75 mg group, 87.5% of patients in the 200 mg group, and 42.86% of patients in the 600 mg group. In contrast, all patients in the placebo group had at least one attack during the trial.

“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,” said Timothy Craig, DO, lead investigator in the trial.

All adverse events (side effects) recorded were either mild or moderate in severity. The percentage of patients experiencing at least one treatment-related adverse event was similar across all groups, with injection site erythema (skin reaction) being the most common (12.5%).

“The findings of this study are very encouraging and we look forward to further research assessing the safety and efficacy of garadacimab,” Craig said.

The trial is still recruiting participants in the U.S., Canada, Australia, Germany, and Israel. More information and contacts are available here.

Garadacimab recently was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) as an investigational therapy for the prevention of both hereditary and non-hereditary (acquired) angioedema. 

“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,” Doyle said. 

CSL Behring also is investigating garadacimab as a potential treatment for other medical conditions in which FXIIa inhibition may be important.