Early Success With New Target in Atopic Dermatitis

— Inhibition of Th2-related inflammation leads to rapid improvement in disease activity


NEW YORK CITY -- An oral drug that targets Th2 activity in atopic dermatitis reduced disease activity by as much as 50% after 6 weeks, results of a small placebo-controlled study showed.

At 4 weeks of treatment with RPT193, the mean Eczema Area and Severity Index (EASI) score had decreased by 36% from baseline, followed by additional improvement over the first 2 weeks after treatment discontinuation to a difference of 53% at 6 weeks. Assessment by the composite SCORAD (Scoring Atopic Dermatitis) index showed a 26% improvement from baseline versus 9% for the placebo group, increasing to almost 40% in the RPT193 at 6 weeks, whereas the placebo effect waned and returned toward baseline values.

Individual components of the SCORAD index improved by 30-50% at 6 weeks, with continued improvement following the end of treatment, said Robert Bissonnette, MD, of Innovaderm Research in Montreal, during the Inflammatory Skin Disease Summit.

"I cannot really say that it is a drug that works because this study was not powered to detect the efficacy, but there was a positive signal, and it was fairly well tolerated," said Bissonnette. "What's very interesting, I think, is a difference in terms of efficacy, which seems to be higher 2 weeks after treatment. This may be due to the fact that the drug is acting on accumulations of cells. What we may be seeing is the fact that we have fewer cells in the dermis after you stop treatment, and then you see additional efficacy."

The continued improvement after treatment stopped is consistent with the drug's unique pharmacokinetics related to targeting Th2 migration and activation through CCR4 signaling, he added.

RPT193 targets the chemokine receptor CCR4, which regulates Th2 migration into inflamed tissues and can enhance cytokine secretion by activated T cells. Besides promoting inflammation, CCR4-induced Th2 migration promotes tissue thickening and itch.

Bissonnette reported findings from a phase Ib trial to evaluate RPT193 activity in patients with moderate-to-severe atopic dermatitis. Investigators screened adults with at least a 12-month history of atopic dermatitis, body surface area (BSA) of at least 10%, EASI score ≥12, and Investigator Global Assessment (IGA) score ≥3.

Data analysis included 31 patients randomized 2:1 to RPT193 or placebo. Treatment continued to day 29, followed by an additional 14 days of follow-up. The primary endpoint was safety, and the trial lacked statistical power to assess any specific endpoint, said Bissonnette.

The patient groups were relatively well balanced, given the small numbers, with no major differences in baseline characteristics. RAPT Therapeutics previously announced the EASI results, and Bissonnette focused on the SCORAD findings.

Developed about 20 years ago, the index has a score range of 0-103 and comprises objective, investigator-assessed, and patient-reported outcomes (PROs). Objective elements consist of BSA and six criteria to assess disease intensity or lesion severity. PROs include sleep loss, pruritus, and a visual analog scale to rate disease activity over the past 3 days.

The study population had a baseline mean SCORAD score of about 24, baseline mean EASI of about 20, BSA of about 24%, and all but five of the 31 patients had a baseline IGA score of 3.

Bissonnette said the only adverse event that occurred in more than one patient in either treatment group was nausea. However, nausea also occurred in healthy volunteers treated with placebo during a preliminary safety study of RPT193, "so it's too early to tell whether this is a real [safety] signal," he noted.

Though no endpoint was prospectively assessed for statistical significance, a post-hoc analysis of the total SCORAD score showed statistically significant improvement in the RPT193 group versus the placebo group at day 43 (P<0.05).

No change in BSA occurred in the placebo group at day 29 or 43, whereas the RPT193 group had about a 20% decrease from baseline at day 29 and a 40% decrease at day 43 (P<0.05). The SCORAD lesion severity score did not change substantially from baseline but decreased by about 20% by day 29 and by about 35% by day 43 in the RPT193 group (P<0.05).

Combined patient ratings for sleep loss and pruritus showed 42.4% improvement from baseline in the RPT193 group at day 29 versus an increase from baseline in the placebo group. By day 43 the composite score had declined by 50% in the RPT193 arm and remained elevated versus baseline in the placebo group (P<0.05). Separate analyses of sleep loss and pruritus showed similar improvement in both outcomes with RPT193 and similar differences from the placebo arm.

During the discussion that followed the presentation, Bissonnette responded to a question about the drug's safety with a description of one RPT193-treated patient who had an exanthematous reaction accompanied by loss of taste and arthralgia. As the symptoms appeared viral, the patient was tested for COVID-19, which yielded a negative result.

Because the drug targets a type of T cell, investigators analyzed T-cell counts in patients treated with RPT193 and did not detect any decreases, Bissonnette added.

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow


The study was supported by RAPT Therapeutics.

Bissonnette disclosed relationships with AbbVie, Arcutis, Arena Pharma, Aristea, Asana BioSciences, Bellus Health, Bluefin Biomedicine, Boehringer-Ingelheim, CARA, Dermavant, Eli Lilly, EMD Serono, Evidera, Galderma, GlaxoSmithKline, Inmagene Bio, Incyte, Kiniksa, Kyowa Kirin, LEO Pharma, Novan, Pfizer, Ralexar, RAPT Therapeutics, Regeneron, Respivant, Sanofi-Genzyme, Sienna, and Target RWE.

Primary Source

Inflammatory Skin Disease Summit

Source Reference: Bissonnette R, et al "RPT193, an oral CCR inhibitor: results from a randomized, placebo-controlled phase Ib monotherapy trial in patients with moderate-to-severe atopic dermatitis" ISDS 2021; Abstract 88.