FDA Sets Review Date for Zoryve in Atopic Dermatitis

The FDA has accepted the supplemental new drug application for Arcutis Biotherapeutics’ Zoryve (roflumilast) cream 0.15% for adults and children aged 6 and up with atopic dermatitis. Regulators have assigned a Prescription Drug User Fee Act (PDUFA) target action date of July 07, 2024.

Atopic dermatitis is a chronic and recurring inflammatory skin condition that requires therapy that is effective, tolerable, and suitable for long-term use by both adults and children. It affects about 9.6 million children and 16.5 million adults in the United States.

Lawrence Eichenfield, M.D.

“Due to its waxing and waning nature, long-term disease control is ideal for the patient versus cyclical treatment, which consists of starting and stopping treatment when skin is controlled and when it is not,” Lawrence Eichenfield, M.D., chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego, professor of dermatology and pediatrics and vice-chair of the Department of Dermatology at UC San Diego School of Medicine, said in a press release.

Roflumilast cream is a next generation topical PDE4 inhibitor. PDE4 is an intracellular enzyme. In people with atopic dermatitis, PDE4 is overly active, which causes increased inflammation and red itchy skin.

Zoryve cream 0.3% is a once-daily non-steroid cream approved to treat plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. For the atopic dermatitis indication, Zoryve was evaluated at lower doses than the approved psoriasis dose: 0.15% for adults and children 6 years of age and older and 0.05% for children aged 2 to 5 years.

Zoryve’s wholesale acquisition cost is $825 per tube. Those with commercial drug insurance may be eligible for the Zoryve Direct Savings Card. Patients may pay as little as $25 if their commercial drug insurance covers Zoryve, and $75 if their commercial drug insurance currently does not. Individual patient savings are limited to $875 per fill and $5,000 in maximum total savings per calendar year.

Related: Zoryve is Now Approved for Children with Plaque Psoriasis

“In clinical trials, roflumilast cream demonstrated rapid and sustained improvement in the signs and symptoms of atopic dermatitis, as well as long-term proactive disease control with twice weekly maintenance dosing,” Eichenfield said. “Roflumilast cream if approved, has the potential to simplify the approach to disease control for children and adults.”

The sNDA for atopic dermatitis is supported by positive results from three phase 3 programs, as well as a phase 2 dose ranging study, and two phase 1 pharmacokinetic studies. INTEGUMENT-1 and INTEGUMENT-2 were two identical phase 3, vehicle-controlled trials evaluating the safety and efficacy of roflumilast cream 0.15% in atopic dermatitis. Roflumilast met its primary endpoint with a validated Investigator Global Assessment – Atopic Dermatitis Success rate of 32.0% compared with a vehicle rate of 15.2% in INTEGUMENT-1 and 28.9% compared with a vehicle rate of 12.0% at week 4, in and INTEGUMENT-2.

More than 30% of people treated with roflumilast cream in each study achieved Worst Itch-Numeric Rating Scale (WI-NRS) Success at week 4, with rapid and significant improvements observed as early as 24 hours following the first application.

In addition, more than 40% of children and adults treated with roflumilast cream achieved a 75% reduction in Eczema Area and Severity Index (EASI-75) at week 4 compared with vehicle with significant results observed as early as week 1 in both studies.

The incidence of treatment emergent adverse events (TEAEs) was low in both active treatment and vehicle arms. There were no adverse reactions in the combined phase 3 pivotal trials that occurred in more than 2.9% of subjects in either arm. The most common adverse reactions included headache, nausea, application site pain, diarrhea, and vomiting.