The FDA has granted breakthrough status to enpatoran, an oral selective toll-like receptor 7/8 inhibitor, for cutaneous lupus erythematosus (CLE).

It is the second biologic to receive the Breakthrough Designation, which could signal a near-term arrival of novel therapies for CLE, which has had no treatment specifically approved for the condition for 50 years. In January, the agency awarded breakthrough status to litifilimab, a humanized immunoglobulin G1 monoclonal antibody targeting blood dendritic cell antigen 2.

“There is major unmet need in treatments for skin manifestations of lupus,” Albert T. Roy, president and CEO of the Lupus Research Alliance (LRA) in New York City, said in a July 9 statement on the news regarding enpatoran. “It is encouraging to see progress in the development and recognition by the FDA to help fill that gap.”

The agency awards the Breakthrough Designation when “preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s),” according to the FDA. Drugs that are awarded that status are given an expedited pathway to market.

David Weinreich, MD, global head of research and development and chief medical officer of Darmstadt, Germany-based Merck KGaA, which makes enpatoran, said in a statement, “We look forward to working with the FDA to potentially bring this much-needed option to patients as quickly as possible.”

An estimated 70% to 85% of patients with lupus have skin manifestations, which can include butterfly rashes, ring-shaped sores, or red, scaly patches and can lead to scarring, skin discoloration, and hair loss.

The FDA based its designation for enpatoran on Merck KGaA’s phase 2 WILLOW study results, which showed clinically meaningful improvement in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity score at week 16. About 91% of patients taking enpatoran achieved a CLASI-50 response at week 24.

Merck KGaA has begun two phase 3 double-blind, randomized, placebo-controlled trials, ELOWEN-1 and ELOWEN-2, investigating enpatoran taken twice daily vs placebo in patients with cutaneous manifestations of lupus with or without systemic disease. The company reported that the first patients received doses in late April.

Lupus Therapeutics, the clinical affiliate of the LRA, is supporting those two pivotal studies.

Biogen has fully enrolled AMETHYST, its phase 3 study of litifilimab. Initial results are expected in 2027.

The LRA, a longtime partner of Biogen, said research it funded helped determine that type 1 interferons — such as those targeted by litifilimab — play a major role in inflammation and drive lupus development.

Another biologic, anifrolumab (Saphnelo), is being evaluated in a phase 3, randomized, double-blind, placebo-controlled study that’s fully enrolled. The company expects to report initial results in December.

The FDA approved a once-weekly autoinjector version of anifrolumab, the Saphnelo Pen, for adults with systemic lupus erythematosus in April.

The experts cited in this article had no relevant disclosures.

Alicia Ault is a Saint Petersburg, Florida-based freelance journalist whose work has appeared in many health and science publications, including Smithsonian.com. You can find her on X @aliciaault and on Bluesky @aliciaault.bsky.social.