Litifilimab Meets Primary Endpoint in Phase 2 Cutaneous Lupus Study
Key Takeaways
- Phase 2 Part A of the AMETHYST study met its primary endpoint, with more patients receiving litifilimab achieving clear or almost clear skin by CLA-IGA-R erythema score at week 16 than those receiving placebo.
- Improvements were also reported across CLASI-based secondary endpoints, although these endpoints were not adjusted for multiplicity and cannot establish statistical significance.
- Victoria Werth, MD, highlighted the treatment’s relatively rapid onset, consistency across disease activity measures, and durability observed during the subsequent treatment period.
Biogen reported positive phase 2 results from Part A of the phase 2/3 AMETHYST study evaluating litifilimab in patients with cutaneous lupus erythematosus (CLE), with the investigational therapy meeting the study’s primary endpoint and showing improvement across several measures of skin disease activity.
Litifilimab is a humanized IgG1 monoclonal antibody targeting blood dendritic cell antigen 2 (BDCA2). The randomized, double-blind, placebo-controlled AMETHYST study evaluates subcutaneous litifilimab plus standard of care compared with placebo plus standard of care. Part A assessed outcomes through week 24; the phase 3 portion remains ongoing and blinded.
Litifilimab Meets Primary CLE Endpoint
At week 16, 14.7% of patients receiving litifilimab achieved a Cutaneous Lupus Activity Investigators’ Global Assessment Revised (CLA-IGA-R) erythema score of 0 or 1, indicating clear or almost clear skin, compared with 2.9% receiving placebo, an 11.8-percentage-point difference (95% CI, 1.39-22.27; P < .05).
Study investigator Victoria Werth, MD, told Practical Dermatology the primary endpoint represented “a very stringent high bar,” adding that improvements across several measures strengthened the overall efficacy findings.
CLASI-50 response at week 24 was achieved by 40.8% of litifilimab-treated participants compared with 21.0% receiving placebo. CLASI-70 responses were reported in 21.7% and 5.8%, respectively. Secondary endpoints were not adjusted for multiplicity and therefore cannot demonstrate statistical significance.
Dr. Werth also pointed to the timing of response as clinically notable.
“They were already getting better within 2 to 4 weeks,” she said of patients initially assigned to placebo who subsequently received litifilimab during the extension period. “And so it’s a very much more rapid onset.”
Adverse events through week 24 occurred in 74.6% of patients receiving litifilimab and 64.7% receiving placebo, with most classified as mild to moderate. Serious adverse events occurred in 6.8% and 2.9%, respectively.
Dr. Werth said the longer-term observations were also encouraging, noting that patients who initially received litifilimab maintained their responses during the subsequent treatment period.
“The durability is something that was sustained over the whole time between 24 and 52 weeks,” she said.