Experts Highlight New Dermatological Treatments, Importance of Clinical Trial Diversity

Experts discussed recent FDA approvals for dermatology treatments and the importance of clinical trial diversity when evaluating potential treatments at the Skin of Color Update in New York City on September 13.

Advances in Topical Therapies

Andrew F. Alexis, MD, MPH, FAAD, Skin of Color Update co-chair, professor of clinical dermatology, and vice-chair for diversity and inclusion at Weill Cornell Medicine, began his presentation by discussing recent topical therapy FDA approvals.

He first highlighted roflumilast and tapinarof, which were each first approved for patients with psoriasis. Roflumilast is a phosphodiesterase 4 (PDE4) inhibitor, resulting in increased intracellular cyclic adenosine monophosphate (cAMP); it prevents the degradation of cAMP, leading to downregulation of inflammatory cytokines. Tapinarof is a nonsteroidal topical treatment that belongs to the class of naturally derived aryl hydrocarbon receptor (AhR) agonists.¹

The FDA first approved tapinarof cream 1% (Vtama; Dermavant Services) as a once-daily topical treatment for adult patients with plaque psoriasis on May 24, 2022, making it the first steroid-free AhR agonist to gain approval.² This was based on data from the phase 3 PSOARING 1 (NCT03956355) and 2 (NCT03983980) clinical trials.³ Across both trials, tapinarof cream 1% demonstrated statistically significant improvement at week 12 in patients’ Physician Global Assessment (PGA) score of “clear” (PGA = 0) or “almost clear” (PGA = 1), with a minimum 2-grade improvement from baseline.

On July 29, 2022, Alexis noted that the FDA approved roflumilast cream 0.3% (Zoryve; Arcutis Biotherapeutics) as a once-daily treatment for patients with mild, moderate, and severe plaque psoriasis aged 12 years and older; it was the first approved topical PDE4 inhibitor.⁴

This approval was based on data from the phase 3 DERMIS-1 (NCT04211363) and DERMIS-2 (NCT04211389) clinical trials.⁵ Significantly more patients treated with roflumilast cream 0.3% achieved Investigator Global Assessment (IGA) success at week 8 (42% in DERMIS-1; 37% in DERMIS-2) than patients in the control group (6% in DERMIS-1; 7% in DERMIS-2; P < .0001 in both studies); IGA success is defined as a score of clear (0) or almost clear (1), with a minimum 2-grade improvement from baseline.

Alexis explained that roflumilast has since been approved to treat patients of other disease states, including seborrheic dermatitis. The FDA approved roflumilast topical foam 0.3% as a once-daily topical treatment for patients aged 9 years and older with seborrheic dermatitis on December 15, 2023.⁶ This was based on the STRATUM trial (NCT04973228), which determined that roflumilast foam 0.3% provided rapid disease clearance as early as week 2 and significant itch relief in as little as 48 hours.⁷

He next highlighted the latest roflumilast approval: roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis (AD) in patients 6 years and older.⁸ The INTEGUMENT-1and INTEGUMENT-2 studies showed that 31.1% of patients in the roflumilast group achieved the primary end point of Validated Investigator Global Assessment-AD (vIGA-AD) success at week 4 compared with 14.1% of the vehicle group.

Alexis concluded by discussing potential future indications of tapinarof and roflumilast. He first highlighted the potential approval of tapinarof cream 1% for AD treatment since Dermavant Sciences announced on April 29 that the FDA accepted its sNDA for tapinarof cream 1% for AD treatment in adult patients and pediatric patients 2 years and older.⁹ Its Prescription Drug User Fee Act (PDUFA) action date is set for the fourth quarter of 2024.

Advances in Biologic Therapies

Alexis then focused on recent biologic therapy approvals, beginning with that of bimekizumb (Bimzelx; Union Chimique Belge [UCB]), a dual inhibitor of interleukin 17A (IL-17A) and 17F (IL-17F), for treating moderate to severe plaque psoriasis in eligible adult patients on October 18, 2023.¹⁰

The approval was supported by the phase 3 BE READY (NCT03410992), BE VIVID (NCT03370133), and BE SURE (NCT03412747) trials. By week 16, a 320 mg dose of bimekizumab administered every 4 weeks was associated with more than 80% of treated patients achieving clear or almost clear skin per Psoriasis Area Severity Index scores of 90% and above (PASI 90) and IGA scores of 0 or 1.

Next, Alexis highlighted the approval of secukinumab (Cosentyx; Novartis) on October 31, 2023, for adult patients with moderate to severe HS.¹¹ The treatment regimen involves 300 mg of secukinumab administered through a subcutaneous injection every 4 weeks. Its approval was based on the results of the phase 3 SUNSHINE (NCT03713619) and SUNSET (NCT03713632) trials, which showed rapid relief from HS symptoms as early as week 2.

Lastly, Alexis discussed the FDA approval of nemolizumab (Nemluvio; Galderma) on August 13, 2024, as a pre-filled pen for subcutaneous injection to treat adult patients with prurigo nodularis every 4 weeks.¹² The approval was based on positive results from the phase 3 Olympia 1 (NCT04501679) and 2 (NCT04501666) trials.

These found that 56% and 49% of patients treated in Olympia 1 and 2, respectively, achieved at least a 4-point itch intensity reduction on the peak-pruritus numerical rating scale at week 16 compared with 16% in both placebo groups.

“Our armamentarium has strengthened greatly, and we’ve been offered so much more for our patients of all skin types, especially our patients with skin of color, who have historically had so many unmet needs in terms of treatment options,” Alexis concluded.

Image credit: Andrey Popov - stock.adobe.com

Keeping Diversity in the Forefront

With the development of new therapies, Valerie M. Harvey, MD, MPH, founder and director of the Hampton Roads Center for Dermatology, reminded audience members during her presentation to ensure their clinical trial populations include patients of diverse backgrounds. To help with this, she explained that the FDA is developing a diversity action plan (DAP) to ensure that pharmaceutical companies enroll more women and people of color in clinical trials.¹³

Under the DAP, companies performing large phase 3 trials must provide the FDA with their plans for enrolling patients considered representative of those who would take the respective product. They are encouraged to include their enrollment goals, rationale, and their plan for meeting these goals.

Although it may be difficult at times to define “adequate” clinical trial diversity in terms of race/ethnicity, Harvey suggested that companies look at the prevalence of the disease across populations to ensure they account for all groups affected.

“When we’re designing these studies, when we’re asking these research questions, it’s really important to engage the community from the outset to really get a sense of what their priorities are, what their concerns are, so that we can build that into the study design,” she said. “I think that is so important to get meaningful diversity and so that we can really translate what we learn from these clinical trials into practice.”

References

1. 1. Elder AJ, Patel P, Daveluy S. Tapinarof. PubMed. Accessed September 13, 2024. https://www.ncbi.nlm.nih.gov/books/NBK594244/
2. Stocum L. Tapinarof cream 1% is FDA approved. Dermatology Times. May 24, 2022. Accessed September 13, 2024. https://www.dermatologytimes.com/view/tapinarof-cream-1-is-fda-approved
3. Lebwohl MG, Stein Gold L, Strober B, et al. Phase 3 trials of tapinarof cream for plaque psoriasis. New England Journal of Medicine. 2021;385(24):2219-2229. doi:10.1056/nejmoa2103629
4. FDA approves Arcutis' Zorvye (Roflumilast) cream 0.3% for the treatment of plaque psoriasis in individuals age 12 and older. Arcutis Biotherapeutics. July 29, 2022. Accessed September 13, 2024. https://www.arcutis.com/fda-approves-arcutis-zoryve-roflumilast-cream-0-3-for-the-treatment-of-plaque-psoriasis-in-individuals-age-12-and-older/
5. Lebwohl MG, Kircik LH, Moore AY, et al. Effect of roflumilast cream vs vehicle cream on chronic plaque psoriasis: the DERMIS-1 and DERMIS-2 randomized clinical trials. JAMA. 2022;328(11):1073-1084. doi:10.1001/jama.2022.15632
6. Smith T. FDA announces approval of roflumilast foam for seborrheic dermatitis. December 15, 2023. Accessed September 13, 2024. https://www.hcplive.com/view/fda-announces-approval-of-roflumilast-foam-for-seborrheic-dermatitis
7. Blauvelt A, Draelos ZD, Stein Gold L, et al. Roflumilast foam 0.3% for adolescent and adult patients with seborrheic dermatitis: a randomized, double-blinded, vehicle-controlled, phase 3 trial. J Am Acad Dermatol. 2024;90(5):986-993. doi:10.1016/j.jaad.2023.12.065
8. McCormick B. FDA approves roflumilast for patients 6 years and older with atopic dermatitis. July 9, 2024. Accessed September 13, 2024. https://www.ajmc.com/view/fda-approves-roflumilast-for-patients-6-years-and-older-with-atopic-dermatitis
9. Dermavant announces FDA acceptance of Supplemental New Drug Application (sNDA) for VTAMA (tapinarof) cream, 1% for the treatment of atopic dermatitis in adults and children 2 years of age and older. April 29, 2024. Accessed September 13, 2024. https://dermavant.com/dermavant-announces-fda-acceptance-of-supplemental-new-drug-application-snda-for-vtama-tapinarof-cream-1-for-the-treatment-of-atopic-dermatitis-in-adults-and-children-2-years-of-age-and-old/
10. Kunzmann K. FDA approves bimekizumb for adults with plaque psoriasis. October 18, 2023. Accessed September 13, 2024. https://www.hcplive.com/view/fda-approves-bimekizumab-adults-plaque-psoriasis
11. Joszt L. Secukinumab gains FDA approval to treat hidradenitis suppurativa. October 31, 2023. Accessed September 13, 2024. https://www.ajmc.com/view/secukinumab-gains-fda-approval-to-treat-hidradenitis-suppurativa
12. McCormick B. FDA approves nemolizumab for adult patients with prurigo nodularis. August 13, 2024. Accessed September 13, 2024. https://www.ajmc.com/view/fda-approves-nemolizumab-for-adult-patients-with-prurigo-nodularis
13. What we're reading: Plan B use plunges; lower drug costs; clinical trial diversity guidance. June 27, 2024. Accessed September 13, 2024. https://www.ajmc.com/view/what-we-re-reading-plan-b-use-plunges-lower-drug-costs-clinical-trial-diversity-guidance