Both doses of the anti-ILT7 antibody daxdilimab reduced CLASI-A scores vs placebo at week 24 in moderate-to-severe, treatment-refractory discoid lupus.
Daxdilimab, an anti-ILT7 antibody depleting plasmacytoid dendritic cells (pDCs), reduced disease activity vs placebo in
Treatment options for DLE remain limited, with clinicians relying largely on older therapies, few of which have been formally studied in randomized trials. pDCs accumulate in the lesional skin of patients with cutaneous lupus and drive type I interferon activity.¹,2 Daxdilimab, developed by Amgen, binds immunoglobulin-like transcript 7 (ILT7), a surface protein expressed only on pDCs, reducing pDC numbers in tissue and blood.¹
“There’s a need for new treatments for discoid lupus and for cutaneous lupus in general,” said Victoria Werth, MD, professor of dermatology at the University of Pennsylvania, in an interview with HCPLive at EADV. “I There has not been a single approved drug in [roughly] 80 years. It’s significant to get approval of new drugs for patients who have refractory disease.”
The multicenter, randomized, double-blind, placebo-controlled phase 2 trial enrolled adults aged 18 to 75 years with chronic, treatment-refractory DLE lasting ≥ 6 months.¹ Eligible patients had active disease, defined as a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score of ≥ 8, and no systemic features.¹
In total, 72 patients were randomized 1:1:1 to low-dose daxdilimab (n = 24), high-dose daxdilimab (n = 23), or placebo (n = 25). Dosing occurred every 4 weeks from day 1 through week 20.¹ Patients had a mean age of 48.8 years and 69.4% were female. Mean baseline scores were 15.2 for CLASI-A and 3.1 for the Cutaneous Lupus Activity Investigator’s Global Assessment (CLA-IGA).¹
Both doses met the primary endpoint of mean change in CLASI-A from baseline to week 24. The least squares mean difference vs placebo was –6.0 for low-dose daxdilimab (90% CI, –8.7 to –3.2; P =.0005) and –5.7 for high-dose daxdilimab (90% CI, –8.5 to –2.9; P =.0012).¹ Separation from placebo emerged as early as week 4, and Werth noted improvement continued through the 24-week study period.
At week 24, adjusted CLASI-50 response rates reached 61.7% with low-dose daxdilimab (P =.0037) and 62.1% with high-dose daxdilimab (P =.0044), compared with 23.7% with placebo.¹ Adjusted CLA-IGA 0/1 response rates were 60.3% (P <.0001) and 51.6% (P =.0007), respectively, vs 8.9% with placebo.¹
“We know a CLASI-50 is significant from a patient perspective,” Werth said. “When you actually look at the patients who got treated and some of the photography, you can really see the improvement is quite dramatic.”
No serious adverse events or deaths were reported. Treatment-emergent adverse events occurred in 58.3%, 56.5%, and 60% in the low-dose, high-dose, and placebo groups, respectively. One patient receiving high-dose daxdilimab discontinued because of grade 3 arthralgia.¹
Diarrhea occurred in 3 patients (13%) in the high-dose group and none in the other arms. Nasopharyngitis was more frequent with placebo (16%) than with daxdilimab.¹ Werth added no cases of herpes zoster were observed, a longstanding concern with therapies targeting interferon production.
Werth described 2 pDC-directed agents in development. Daxdilimab depletes pDCs, whereas litifilimab, an antibody against blood dendritic cell antigen 2 (BDCA2), triggers receptor internalization and downregulates pro-inflammatory pDC activity.
Given the rapid onset of response and the safety profile observed, Werth said daxdilimab and other pDC-targeting drugs could fit early in the DLE treatment cascade. She also pointed to agents targeting toll-like receptor (TLR) 7/8 entering phase 3. She credited FDA acceptance of the CLASI as a primary skin outcome with enabling the current wave of cutaneous lupus trials.
“There will be a lot of work to do to understand the nuances between these drugs,” Werth said.
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