All signs continue to point forward for Biogen’s initial foray into lupus, as litifilimab elicited clear or almost clear skin within one year in patients with cutaneous lupus in a mid-stage study. Data from two Phase 3 studies of systemic lupus are expected by the end of the year.
Confidence in Biogen’s litifilimab is growing after the candidate helped more than a quarter of patients with an autoimmune disease achieve clear or almost clear skin after one year in a mid-stage study.
The results build momentum ahead of key late-stage readouts for the asset in cutaneous lupus erythematosus (CLE), said BMO Capital Markets, which forecasts potential blockbuster sales for the asset.
“We view deepening responses and favorable safety as meaningfully positive ahead of Ph3 data expected in 1H27,” the analysts wrote in a Friday note to investors. Last-stage data for litifilimab in the systemic form of lupus, meanwhile, are expected by the end of this year.
In the Phase 2a part of the Phase 2/3 AMETHYST trial, 27.2% of trial participants saw clear or almost clear skin on a key disease activity scale within a year of starting treatment with litifilimab, meeting a secondary endpoint of the study. This is up from 19% of patients at the trial’s 24-week mark, Biogen reported on Friday. Treatment benefits also deepened on another CLE scale, with 28.8% of patients enjoying a 70% or greater reduction in disease severity at one year compared to 21.7% at week 24. The study included 93 adults with CLE who could not tolerate or whose disease had not responded to antimalarial medicines, the current standard of care for the disease.
The Phase 2 study met its primary endpoint of reduced disease activity compared to placebo, Biogen reported in March, with more litifilimab-treated participants seeing clear or almost clear skin at week 16.
At one year, not only did the results improve, but in patients who started the study on placebo and transitioned to litifilimab halfway through, the benefits were swift.
“Encouragingly, the crossover cohort showed clinical improvement as early as four weeks, supporting rapid onset of treatment response,” BMO said on Friday.
As for safety, litifilimab’s profile “remained consistent with previous studies, with no new safety signals identified,” Biogen said in its release. The majority of adverse events (AEs) were mild or moderate, though serious AEs occurred in 3.4% of 88 patients during the extended treatment period. The most common AEs were the common cold, flu and joint pain.
CLE is a serious skin disorder that causes disfigurement stemming from hair loss, permanent scarring and abnormal skin color. It occurs when the immune system attacks healthy skin and can happen either independently or alongside the most common form of lupus, systemic lupus erythematosus (SLE). Litifilimab selectively targets BDCA2 receptors on a certain immune cell to reduce inflammation, according to Biogen. There are currently no approved drugs for CLE.
Biogen is trying to change that. With a deep history in another autoimmune disease, multiple sclerosis, litifilimab represents a big push by the biotech into lupus. The asset is also being studied in SLE—the most common form of lupus—in the Phase 3 TOPAZ-1 and TOPAZ-2 trials, both of which were scheduled to wrap up last month and are expected to read out in Q4.
“Ultimately, BIIB could consider a BLA even if one study was (+),” Jefferies analysts said in a Friday note.
All in on lupus
Biogen has been working in lupus for more than a decade, Diana Gallagher, senior vice president of the company’s Multiple Sclerosis and Immunology Disease Unit and Alzheimer’s and Dementia Disease Unit, told BioSpace in March. Now, the company has reached an “inflection point,” she said.
Having earned the FDA’s Breakthrough Therapy Designation, “[litifilimab] represents one of BIIB’s several $1B+ pipeline programs that could garner more credit in 2026-27,” Jefferies said on Friday, adding that the durable Phase 2 data support the drug’s differentiation in CLE.
Litifilimab in CLE is easily a $1 billion-plus opportunity for Biogen, the analysts added, noting the lack of approved drugs and U.S. prevalence of around 153,000 patients, “50% of whom do not respond to therapies like antimalarials/topicals.”
Meanwhile, Jefferies said, more than 200,000 people in the U.S. have SLE. The market’s two currently approved drugs, GSK’s Benlysta and AstraZeneca’s Saphnelo, collectively reel in more than $3B per year—figures that support Jefferies’ projection of $2 billion-plus in peak sales for litifilimab across the two indications.
In addition to litifilimab, Biogen is also partnered with UCB Pharma on dapirolizumab pegol, which blocks CD40L—a protein in B and T cells—in an attempt to lessen lupus disease activity. Two Phase 3 trials in SLE, PHOENYCS FLY and PHOENYCS GLIDE, are set for completion in 2028 and 2030, respectively.
