Litifilimab extended skin responses through 52 weeks in phase 2 AMETHYST data in cutaneous lupus erythematosus, with phase 3 results expected in 2027.
Litifilimab, an investigational monoclonal antibody, maintained and extended skin responses through 52 weeks in the phase 2 portion of the phase 2/3 AMETHYST study in cutaneous lupus erythematosus (CLE), according to data presented Oct. 2 at the European Academy of Dermatology and Venereology Congress in Vienna.1
No targeted therapy is approved for CLE, and the pivotal phase 3 portion of the study, expected to read out in the first half of 2027, will determine whether Biogen’s candidate can become the first new drug for the disease since the 1950s.1
"Access to 52-week data is critical when evaluating a treatment for a lifelong, chronic disease like cutaneous lupus erythematosus, which can cause permanent scarring and disfigurement that many patients will carry with them forever,” said Joseph F. Merola, MD, MMSc, a dermatologist and rheumatologist who is president of the Rheumatologic Dermatology Society.1 “That is why achieving clear or almost clear skin, which is rarely seen in CLE, is a truly transformative treatment goal for this disease. It is highly encouraging to see continued improvement in skin clearance with litifilimab treatment – with over a quarter of participants reaching clear or almost clear skin – and data supporting litifilimab's long-term safety profile."
The phase 2 portion enrolled 93 adults with active subacute or chronic CLE whose disease was refractory or intolerant to antimalarial therapy. Participants received subcutaneous litifilimab or placebo every 4 weeks through week 20, with an additional dose at week 2, and all participants received litifilimab from week 24 onward.1
The study met its primary endpoint at week 16. At week 24, 21.7% of litifilimab recipients achieved at least a 70% reduction in the Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score (CLASI-70) vs 5.8% with placebo.2
Among participants treated from randomization, the proportion with clear or almost clear skin, measured by an investigator global assessment of erythema, rose from 19.0% at week 24 to 27.2% at week 52. CLASI-70 response rose from 21.7% to 28.8%. Participants who switched from placebo at week 24 showed improvement within 4 weeks, and 33.7% had clear or almost clear skin by week 52.1
Most adverse events (AEs) were mild or moderate. Serious AEs occurred in 3 of 88 participants (3.4%) during the extended treatment period, the most common events were nasopharyngitis, influenza, and arthralgia, and no new safety signals were identified.1
"Living with cutaneous lupus erythematosus carries a heavy physical toll, including dyspigmentation, pain, and scarring, which can be associated with comorbidities like depression and anxiety that can have a profound impact on daily life,” said Daniel Quirk, MD, chief medical officer at Biogen.1 “These 52-week data reinforce litifilimab's potential to deliver rapid improvement and demonstrate its durable skin clearance effects. We are encouraged by these results that build on findings in earlier studies as we anticipate the upcoming Phase 3 study results that reflect our commitment to advancing targeted therapies for serious autoimmune conditions."
In CLE, the immune system attacks healthy skin, causing rash, pain, itching, and sensitivity to sunlight, and the disease can lead to hair loss, permanent scarring, and abnormal pigmentation. Patients are largely managed with therapies not developed specifically for the condition.1
"People living with cutaneous lupus erythematosus face debilitating symptoms, including scarring, hair loss, and extreme sensitivity to light, yet they have long relied on treatments not specifically developed or studied for CLE,” said Albert T. Roy, president and CEO of the Lupus Research Alliance.1 “The new data on litifilimab are encouraging because they point to the potential for both rapid symptom relief and durable improvement for people living with this condition. We look forward to seeing additional data from the Phase 3 study."
Litifilimab binds blood dendritic cell antigen 2 on plasmacytoid dendritic cells, which produce type I interferons and act early in the inflammatory cascade of lupus.1,3 It is being developed as a once-monthly subcutaneous therapy for CLE and systemic lupus erythematosus.1
In the phase 2 LILAC trial, 132 participants with CLE were randomly assigned to 1 of 3 litifilimab doses or placebo. All 3 doses reduced CLASI activity scores more than placebo at week 16, and reported adverse events included hypersensitivity reactions and oral herpes infections.3
The FDA granted litifilimab Breakthrough Therapy designation for CLE in January 2026.1
The cohort was small, and because all participants received litifilimab after week 24, the 52-week results lack a placebo comparison and have not been peer reviewed. The phase 3 portion of AMETHYST remains blinded, and litifilimab is not approved by any regulatory authority.1
