Litifilimab in Cutaneous Lupus Erythematosus Save
Transcription
Hi, I'm Joe Morola. I'm a dermatologist and rheumatologist here at UT Southwestern in Dallas. Uh, just reporting back on some interesting news from the recent AAD meeting. Uh, we got a little glimpse at the data from the Amethyst study. It's a study in cutaneous lupus which, uh, right off the bat is unique in that — it's pretty uncommon that we get a chance to see data from a dedicated CLE trial. So this is a study of patients with CLE plus or minus systemic manifestations. I'll come back to that. Um, looking at a drug called litifilimab. Um, this is a BDCA2 inhibitor which essentially inhibits the function of plasmacytoid dendritic cells, um, and as you would imagine thereby decreasing type 1 interferon, a couple of other likely relevant cytokine chemokines downstream. This is a 24-week look at um data in a 52-week study, uh, from the Amethyst program as I mentioned. I'll share a little bit of data.
Um, so essentially, uh, the study is — or was — in adults, um, 18 or older with histologically confirmed cutaneous lupus, and um they didn't have to have systemic manifestations. They could or could not have systemic manifestations. All of them had a CLASI-A of 10 or greater, which means moderate to severe disease, and were refractory or intolerant to antimalarials. Uh, and many were on stable background, uh, standard of care therapies — placebo-controlled, uh, double-blind trial — and we're, um, uh, here having a look at um the 24-week data and a few earlier time points as well.
So what was interesting about the study — first of all, these patients had pretty significant skin lupus. So all of them, the mean CLASI was over 20, which means that that puts them in the severe category and above. Um, all had moderate-severe CLASI-A um severity, and you know, who were these patients? So about half of them at least had discoid lupus, um, about a third of them had subacute cutaneous lupus, and the remainder had some overlap between the two. These are not patients with acute cutaneous lupus malar eruption. These are really chronic cutaneous discoid lupus and subacute cutaneous lupus patients. So interesting, uh, you know, interesting again to be able to see this population in a dedicated study.
Uh, primary endpoint was the CLASI-A, uh, looking at um clear or almost clear. So the first uh data that we saw was the week 16 primary endpoint, which showed around 15% compared to 2.9%, uh, uh, in the — you know, active litifilimab versus placebo — achieving that clear or almost clear. At week 24, about 20% had achieved clear or almost clear, and I'll just, you know, insert a commentary that this is a very high bar. I mean, these patients essentially have no uh residual disease. Um, and we started to see separation as early as week four.
Um, the other data point to mention here is CLASI-50. So this is probably a little bit more of a reasonable endpoint to be looking at in 2026. You know, this is not like psoriasis where we're talking PASI 90s and hundreds yet. But CLASI-50, known to be a meaningful clinical endpoint. Uh, week 24 we saw 40% of patients achieving the CLASI-50 compared to about 20% on placebo, and that separation again happened as early as week four, with about 20% reaching it at week four compared to 5% in placebo.
Um, safety looked good. Uh, we've seen data from this program from SLE, um, and some other smaller uh studies including a CLE program. You know, mostly we're talking about — um, you know, we're looking out, of course, as you'd imagine with the mechanism, for HSV, VZV — um, there were no cases of opportunistic infections, disseminated zoster, etc. Um, so really overall well tolerated, favorable safety profile. Uh, and I'll just add to that that many of these patients were on background baseline therapy. Uh, methotrexate, mycophenolate, in some cases, uh, the majority of them on concurrent hydroxychloroquine. Still, safety uh looked reassuring.
So I think my takeaway from this is very, very uh encouraged, uh, to see, uh, you know, a program really focused on CLE. We have nothing FDA approved for cutaneous lupus as a standalone. Uh, this program got um accelerated status from uh the FDA, and we're we're hopeful to have something in this space. So stay tuned, I guess, for uh for more phase three data.
Um, so essentially, uh, the study is — or was — in adults, um, 18 or older with histologically confirmed cutaneous lupus, and um they didn't have to have systemic manifestations. They could or could not have systemic manifestations. All of them had a CLASI-A of 10 or greater, which means moderate to severe disease, and were refractory or intolerant to antimalarials. Uh, and many were on stable background, uh, standard of care therapies — placebo-controlled, uh, double-blind trial — and we're, um, uh, here having a look at um the 24-week data and a few earlier time points as well.
So what was interesting about the study — first of all, these patients had pretty significant skin lupus. So all of them, the mean CLASI was over 20, which means that that puts them in the severe category and above. Um, all had moderate-severe CLASI-A um severity, and you know, who were these patients? So about half of them at least had discoid lupus, um, about a third of them had subacute cutaneous lupus, and the remainder had some overlap between the two. These are not patients with acute cutaneous lupus malar eruption. These are really chronic cutaneous discoid lupus and subacute cutaneous lupus patients. So interesting, uh, you know, interesting again to be able to see this population in a dedicated study.
Uh, primary endpoint was the CLASI-A, uh, looking at um clear or almost clear. So the first uh data that we saw was the week 16 primary endpoint, which showed around 15% compared to 2.9%, uh, uh, in the — you know, active litifilimab versus placebo — achieving that clear or almost clear. At week 24, about 20% had achieved clear or almost clear, and I'll just, you know, insert a commentary that this is a very high bar. I mean, these patients essentially have no uh residual disease. Um, and we started to see separation as early as week four.
Um, the other data point to mention here is CLASI-50. So this is probably a little bit more of a reasonable endpoint to be looking at in 2026. You know, this is not like psoriasis where we're talking PASI 90s and hundreds yet. But CLASI-50, known to be a meaningful clinical endpoint. Uh, week 24 we saw 40% of patients achieving the CLASI-50 compared to about 20% on placebo, and that separation again happened as early as week four, with about 20% reaching it at week four compared to 5% in placebo.
Um, safety looked good. Uh, we've seen data from this program from SLE, um, and some other smaller uh studies including a CLE program. You know, mostly we're talking about — um, you know, we're looking out, of course, as you'd imagine with the mechanism, for HSV, VZV — um, there were no cases of opportunistic infections, disseminated zoster, etc. Um, so really overall well tolerated, favorable safety profile. Uh, and I'll just add to that that many of these patients were on background baseline therapy. Uh, methotrexate, mycophenolate, in some cases, uh, the majority of them on concurrent hydroxychloroquine. Still, safety uh looked reassuring.
So I think my takeaway from this is very, very uh encouraged, uh, to see, uh, you know, a program really focused on CLE. We have nothing FDA approved for cutaneous lupus as a standalone. Uh, this program got um accelerated status from uh the FDA, and we're we're hopeful to have something in this space. So stay tuned, I guess, for uh for more phase three data.
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