Phase 2 Trial Tests Daxdilimab as Potential DLE Therapy

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RECAST DLE targets skin disorder discoid lupus erythematosus

by Steve Bryson PhD | January 5, 2023

The first patient has been enrolled in RECAST DLE, a Phase 2 study evaluating daxdilimab, a potentially first-in-class therapy for moderate-to-severe discoid lupus erythematosus (DLE), a form of lupus that affects the skin.

Horizon Therapeutics, the therapy’s developer, expects to enroll about 100 DLE patients, ages 18–75 whose disease is unresponsive to current treatments, into RECAST DLE (NCT05591222). Recruitment is ongoing in Indiana, Minnesota, and Missouri, with additional sites across the U.S. and Canada to follow. More information about locations and contacts is available here.

“There is a tremendous unmet medical need for safe treatments for DLE,” Benjamin Chong, MD, an associate professor in the department of dermatology at the University of Texas Southwestern Medical Center, said in a press release. “This trial will help evaluate the potential of daxdilimab to meet this need.”

DLE is an inflammatory skin condition marked by lesions that result in scarring, mainly on sun-exposed areas of the face, ears, and scalp. It can lead to permanent hair loss and skin discoloration. DLE can occur as part of systemic lupus erythematosus (SLE) which affects internal organs, develop on its own, or eventually lead to SLE in a small percentage of cases.

DLE occurs four times more often in women than men, and the condition is more prevalent among non-Latino Black and Latino populations. So far, there are no approved therapies to treat DLE.

“DLE is one of the most challenging scarring skin diseases because there is no curative treatment,” Chong said. “It causes round, inflammatory lesions that favor the scalp, face and ears and is associated with a diminished quality of life in patients.”

“DLE can lead to alopecia or permanent hair loss and skin dyspigmentation,” added Horizon’s senior vice president of clinical development Theresa Podrebarac, MD.

Daxdilimab is an antibody-based medicine designed to deplete plasmacytoid dendritic cells (pDCs), a type of immune cell found in DLE skin lesions. pDCs normally release high levels of an immune signaling protein called interferon in response to a viral infection. Still, they also can worsen certain autoimmune diseases like lupus, whereby high interferon is a sign of DLE or SLE activity.

“Plasmacytoid dendritic cells, or pDCs, are reported to be abundant in DLE skin lesions while interferon levels are elevated and daxdilimab has been shown to deplete pDCs,” Podrebarac said.

To be eligible for RECAST DLE, patients must have a diagnosis of moderate-to-severe DLE for six months or more before the study begins, but have not responded to current treatment.

Diagnosis must be supported by a biopsy and/or a clinical feature score of 7 or more on the DLE Classification Criteria (DLECC) scale, which assesses scarring, scar location, and skin discoloration.

Study timeline

Participants will be assigned randomly to receive one of two daxdilimab doses, or a placebo, administered by subcutaneous (under-the-skin) injection over 24 weeks (about six months). Then, all participants will receive daxdilimab for another 24 weeks, followed by an eight-week assessment period.

The study’s primary goal is to assess the effects of daxdilimab in the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score after 24 weeks, compared with placebo. CLASI-A measures lupus skin disease activity, with higher scores indicating more active and skin-damaging disease.

Secondary measures, also evaluated after 24 weeks, include the proportion of participants who achieved a 50% or higher reduction in CLASI-A score and reached low scores on the Cutaneous Lupus Activity-Investigator’s Global Assessment (CLA-IGA) scale. Researchers also will assess a change in the Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE), another measure of DLE activity.

In addition to safety, levels of daxdilimab in the bloodstream will be measured over 48 weeks.

“Daxdilimab is also being investigated in other autoimmune conditions that are driven by high levels of interferon, including alopecia areata, dermatomyositis, lupus nephritis and systemic lupus erythematosus,” Podrebarac said.

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