Penn Medicine, Philadelphia: New Drug Shows Promise Against Autoimmune Skin Disease

An experimental drug called litifilimab (known as BIIB059) could be a powerful long-term treatment for cutaneous lupus erythematosus (CLE), a form of lupus that occurs in the skin and can severely impact quality of life, according to a study from the Perelman School of Medicine at the University of Pennsylvania and the Corporal Michael J. Creszcenz VAMC. The study drug was able to decrease CLE activity in the skin. The results, published in the New England Journal of Medicine, are promising since current treatments for the disease are not always very effective.

“Some patients in our trial saw huge improvements within a month,” said Victoria Werth, MD, a professor of Dermatology at Penn and the chief of Dermatology at the Corporal Michael J. Creszcenz VAMC. “The study showed the drug decreased CLE activity relative to a placebo.”

CLE can occur both in the presence of or absence of systemic lupus erythematosus (SLE).

“CLE can cause scarring, atrophy in the skin, and skin discoloration, as well as permanent hair loss. These impacts on physical appearance also affect mental and emotional health and well-being.

The study ran for 16 weeks with 132 participants. Improvements began to appear within weeks, with the most impactful improvements seen at the 12 and 16-week mark.

Existing therapies for CLE, including antimalarial medications like hydroxychloroquine, immunosuppressives, and steroids have had limited or inconsistent effectiveness or frequent side effects. Litifilimab, however, works differently. As part of a class of drug therapies known as humanized monoclonal antibodies, litifilimab is an antibody that targets the blood dendritic cell antigen 2 (BDCA2) receptor on plasmacytoid dendritic cells, leading to downregulation of pro-inflammatory proteins that are believed to be key culprits behind the damaging inflammation associated with CLE.

“Not only do the available drugs not always work, but they are also not always well tolerated,” said Werth. “Sometimes, a patient may have to move up to immunosuppressants, and those have a lot of side effects like higher risk of infection. So being able to develop a different approach could be pivotal.”

This multisite trial was the first successful randomized phase 2 trial of any new CLE-specific systemic treatment. No new drugs have been approved specifically for CLE for over 50 years, and the few available are used off label or were grandfathered into use. According to Werth, a key to the trial’s success was the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A), a measurement tool Penn Medicine researchers helped develop. Readings in 13 skin regions generate CLASI-A scores ranging from 0 to 70, with higher scores indicating more widespread or severe disease. The tool empowered investigators to more precisely and accurately characterize CLE disease activity including hair loss.

With these promising results, the company Biogen, which funded the study and developed litifilimab, will likely take this medication to a further trial, according to Werth.