Horizon: Phase 2 trial of daxdilimab in SLE fails to meet main goal
No disease activity difference among proportion of patients on therapy, placebo
A Phase 2 clinical trial assessing the safety and effectiveness of daxdilimab for systemic lupus erythematosus (SLE) didn’t show a statistically significant difference between the experimental therapy and a placebo regarding the proportion of patients who showed signs of reduced disease activity while lowering their daily corticosteroid dose. The study failed to meet its main goal.
The Phase 2 trial (NCT04925934), which reported no safety concerns, enrolled SLE patients with moderate to severely active disease. Some 214 patients were randomized into three parallel groups to receive either 200 mg of daxdilimab as a subcutaneous (under the skin) injection every two weeks, 200 mg every 12 weeks, or a placebo every four weeks.
The study’s main goal was to assess the proportion of patients achieving a British Isles Lupus Assessment Group 2004 Index-based combined lupus assessment (BICLA) response and lowering their daily oral glucocorticoid dose to less than 7.5 mg over 48 weeks, or nearly a year. BICLA is a composite measure of SLE disease activity.
What’s next for daxdilimab?
While the trial’s main goal wasn’t met, numerical differences were seen in other endpoints, including in the proportion of patients who achieved an SLE Responder Index of 4 (SRI-4) response and in other measures of lupus activity, and in the proportion who saw a reduction in their corticosteroid dosage.
“While we are disappointed that the trial did not meet its primary endpoint, we will continue to work with investigators to assess these data to determine next steps for our SLE clinical program,” Elizabeth H.Z. Thompson, PhD, executive vice president of research and development at Horizon Therapeutics, daxdilimab’ developer, said in a company press release. “I would like to thank the patients and investigators for their participation in the trial.”
Inflammatory responses in SLE are linked to interferons, a group of immune-signaling molecules. Daxdilimab is an antibody-based therapy crafted to deplete plasmacytoid dendritic cells, a type of immune cell that releases excessive amounts of interferons. Such depletion could disrupt the cycle of inflammation that results in tissue-damaging inflammation in a number of autoimmune conditions.
Horizon said it would continue to assess the trial’s full dataset, while daxdilimab studies in lupus nephritis and discoid lupus erythematosus continue. The company also plans to investigate its potential for nonlupus indications.
The global Phase 2 trial (NCT05540665) in lupus nephritis, a lupus complication marked by kidney damage, enrolled its first patient in May. It’s evaluating the safety and effectiveness of the prospective first-in-class therapy for people with active, proliferative lupus nephritis. Horizon expects to enroll about 210 patients, ages 18-80, in the study, which is anticipated to last two years.
Earlier this year, the first patient enrolled in a Phase 2 trial (NCT05591222) testing daxdilimab in people with moderate to severe discoid lupus erythematosus, which affects the skin. The study seeks to enroll about 100 patients, ages 18-75, whose disorder is unresponsive to existing therapies.