Panel Focuses on Burgeoning Therapies in Atopic Dermatitis

A panel at Revolutionizing Atopic Dermatitis 2023 reviewed treatments expected to come to market within the next year as well as investigational therapies that are in trials for atopic dermatitis (AD)

Led by Melinda Gooderham, MD, MSc, FRCPC, and David Rosmarin, MD, the session reviewed non-steroidal topicals and biologics.

Gooderham began by speaking about medications that are expected to be available by 2024. Non-steroidal topicals were her first focus, including tapinarof and roflumilast.

Tapinarof, which has been approved for treatment of plaque psoriasis in adults, has undergone phase 3 trials for the treatment of AD within the ADORING 1 and ADORING 2 trials for patients aged 2 years and older. In presented numbers testing tapinarof 1%, the ADORING 2 trial found that 46.4% had achieved Validated Investigator Global Assessment for atopic dermatitis (vIGA-AD) success after 8 weeks compared with 18% in the vehicle (the inactive or neutral substance used as a control). The secondary endpoints of Eczema Area and Severity Index (EASI) 75 score and Peak Pruritus Numerical Rating Scale score found 59.1% success and 52.8% success compared with 21.2% and 24.1% in the control, respectively.

Folliculitis was reported in 9% of the tapinarof group, but overall, she said, there were very low rates of adverse events (AEs).

Roflumilast is another treatment expected within the year. It has previously been approved for treatment of plaque psoriasis. The INTEGUMENT 1 and 2 studies tested the treatment in patients aged 6 years and older in a 0.15% dose over the course of 4 weeks. The INTEGUMENT 1 and INTEGUMENT 2 trials had 43.2% and 42.0% of patients who had achieved an EASI of 75 compared with 22.0% and 19.7% using the controls, respectively. An improvement in itch was also found within 24 hours of applying roflumilast 0.15% cream.

Gooderham also reviewed phase 3 trials for lebrikizumab, ADvocate 1 and 2 studies. Both met their primary endpoints of positive Investigator Global Assessment (IGA) response and EASI 75 response compared with the placebo. AEs were mild to moderate but Gooderham warned of the higher rate of conjunctivitis. The Adhere study also met its primary endpoints of positive IGA and EASI 75 response compared with the placebo. The lone trial for nemolizumab has similarly gone well; 2 additional trials are ongoing.

In his half of the talk, Rosmarin reviewed treatments that are currently in the early stages of development.

Along with previously discussed developments in roflimulast, patients aged 2 to 5 years could also have access to the treatment soon, as the treatment is currently undergoing a phase 3 trial. Treatment for hand eczema is currently being tested with delgocitinib, which is in a phase 3 trial. The results found that patients had an IGA clear/almost clear of 19.7% at week 16 compared with 9.9% in the control vehicle.

“You may say that doesn’t sound as good as some of our other meds. Well, we all know hands are much harder to treat. So these results still are significant and meaningful for patients. It’s just that hands are just harder to reach those endpoints,” said Rosmarin.

Asivatrep 1% had promising results in a Korean study of patients with AD aged 12 years and older, as the mean EASI reduction was 44.3% with the treatment compared with 21.4% in the placebo; IGA clear/almost clear was 36% compared with 12.8% in the placebo. It also had a good safety profile.

Rosmarin also highlighted oral medications. The oral medications primarily target 1 of 3 areas—microbial, itch, and adaptive immune system. “Often patients want an oral option, even though us dermatologists, we love our topicals,” said Rosmarin.

EDP1815 initially was found to have promising results in reducing EASI scores and a good safety profile. However, the medication is close to failing in its phase 2 trial, according to Rosmarin, which led to his conclusion that oral medications targeting the microbial will likely not work in the future. The company developing the product, Evelo Biosciences, reported in February that EDP1815 missed its primary endpoint.

Medications that targeted itch include tradipitant and difelikefalin. Although tradipitant "did not show a difference in the intention-to-treat analysis of the worst itch," Rosmarin said, researchers found that those who had mild AD lesion severity had improved itch and sleep when using the medication, which indicates that it could help patients with a high itch burden but not a high AD burden. Difelikefalin is a medication approved by the FDA for itch in moderate to severe pruritus. A trend of improvement was found in patients using this medication.

Rosmarin said that the results of these early trials make him hopeful about future treatment that targets itch in particular. “Maybe it makes sense that this is a strategy for those in that subpopulation that have a low IGA with a really high itch burden,” said Rosmarin.

Medications targeting adaptive immune response were also highlighted. Rosmarin said that he was most excited by the results of RPT193, which found that the EASI score for the RPT193 treatment was 43.6% better compared with the placebo treatment after 43 days, 20 of which were follow-up after treatment. More than 60% of the patients using RPT193 had a proportion of EASI 50 after follow-up.

Rosmarin concluded by saying that this was an exciting time to be involved in new treatments for AD. “There’s a lot of great medicines on the horizon. Obviously some of these medicines aren’t going to pan out but whatever we get really is promising for the future and it’s going to be good for providers…and it’s certainly going to be better for the patients,” he said.