Roflumilast Foam 0.3% Secures FDA Primary Approval to Treat Seborrheic Dermatitis

Arcutis Biotherapeutics today announced the FDA approval of roflumilast foam 0.3% (ZORYVE) for the treatment of seborrheic dermatitis in patients aged 9 years and older.1 Notably, roflumilast foam 0.3% is a once-daily steroid-free foam and the first drug approved by the FDA for seborrheic dermatitis with a new mechanism of action in over 2 decades.

Seborrheic dermatitis is one of those issues that seems trivial and can be ignored, but causes great distress and discomfort to patients. Itching, redness, and peeling cause a significant impact on quality of life. Making matters more difficult, many of our current treatments are formulated as creams, ointments, or oils. While those may be ideal in some situations, for many patients they’re extremely unpleasant on the scalp, says Peter Lio, MD, clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School. of Medicine, Periodicals of Dermatology. “To have a new, cosmetically elegant foam formulation and once-daily application is very exciting. Moreover, a non-steroidal drug like roflumilast seems ideal for this role, with a very -favorable safety profile and the ability to use it on the face for longer periods of time safely.

Roflumilast foam provides rapid pain relief and significant reduction in itching. In the roflumilast foam-treated arm of the pivotal phase 3 STRATUM study (NCT04973228), at week 8, nearly 80% of patients met the primary efficacy endpoint of IGA Success and just over 50% of patients reached complete clearance .

Most patients have itching, scaling, and redness that is very unpleasant and can be difficult to address due to the nature of the hairy scalp. Many patients express frustration with oil formulations–that it leaves hair greasy and flat, that it stains pillowcases, and that it’s really unpleasant to use. Many patients also desire non-steroidal treatment options, especially for those who also have facial seborrheic dermatitis involvement. While not necessarily a replacement, a non-steroidal option can be used intermittently to provide breaks from steroids in some patients as well, Lio said.

In exclusive interviews withPeriodicals of DermatologyShawn Kwatra, MD, and Christopher Bunick, MD, PhD, discuss the importance of historical approval and the unique mechanism of action of roflumilast foam as a phosphodiesterase-4 (PDE4) inhibitor.

Celebrating a Historic Moment

Shawn Kwatra, MD, associate professor of dermatology at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Itch Center, in Baltimore, Maryland, emphasized the incredible importance of the approval of roflumilast foams for seborrheic dermatitis , a common skin condition with no specific FDA-approved therapy.

We also have to applaud Arcutis as a company for being able to take a chance on entering a new indication and being able to help develop the field, validate instruments, and take that chance. I think it is very important for dermatology that we move forward as a field with new therapeutics for our orphan conditions. I have seen this happen in prurigo nodularis. It’s exciting for this to happen with seborrheic dermatitis because usually, when there’s a big investment made in understanding a disease and clinical trials, then we learn more about what’s really going on. So, this is a very historic day for us that we have a new therapeutic, Kwatra said.

Dive into the Mechanism of Action

Christopher Bunick, MD, PhD, associate professor of dermatology and physician-scientist at the Yale School of Medicine in NewHaven, Connecticut, discussed in depth the mechanism of action of roflumilast foam and its ability to boost cAMP, and therefore create a anti-inflammatory effect.

That is why seborrheic dermatitis patients will see a very good reduction in the redness of the skin lesions, and it will also reduce the scaling effect from the inflammation itself. What makes roflumilast’s mechanism of action really stand out is that at the molecular level, roflumilast is anchored to the PDE4 binding site by 3 key contacts. Those 3 key contacts help give it a high binding affinity that translates, we think clinically, into the potency we see with roflumilast, Bunick said.

Seborrheic dermatitis causes red spots covered with large, oily, scaly yellow-gray scales, and constant itching. In skin-colored patients, the inflamed areas may not appear red, but instead may appear pink, slightly purple, or darker in color than the surrounding skin. Seborrheic dermatitis occurs on areas of the body that have sebaceous glands, including the scalp, face (most prominently on the nose, eyebrows, ears, and eyelids), upper chest, and back. Because of the nature of the hair around these areas, topical creams, gels, and ointments are difficult to apply.

According to the announcement, Arcutis aims to make makeroflumilastfoam widely available through major wholesalers and dermatology pharmacy channels as a new treatment option by the end of January 2024. The ZORYVE Direct Program helps patients access their Arcutis prescription drug. For patients with seborrheic dermatitis prescribed roflumilast, the patient support program helps navigate the payer process, assists patients with compliance, and includes the ZORYVE Direct Savings Card Program, which can help reduce out-of-pocket costs for eligible commercially insured patients. Arcutis will continue to offer the Arcutis Cares patient assistance program that provides roflumilastat at no cost to financially eligible uninsured or underinsured patients.

The approval of roflumilast foam is based on positive results from the phase 2 Trial 203 and phase 3 STRAUM trial. Both trials were parallel-group, double-blind, vehicle-controlled studies evaluating the safety and efficacy of roflumilast foam 0.3% in seborrheic dermatitis. Overall, both studies enrolled 683 adults and adolescents aged 9 years and older.

The STRATUM study met its primary endpoint, with nearly 80% of patients treated with roflumilastfoam achieving Investigator Global Assessment (IGA) Success at week 8 (79.5% roflumilast foam vs. 58.0% vehicle; P<0.0001). In Trial 203, 73% of patients treated with roflumilastfoam achieved IGA Success (73.1%roflumilastfoam versus 40.8% vehicle; P<0.0001.) IGA Success was defined as an IGA score of Clear (0) or Almost Clear (1), plus a 2-grade improvement in IGA score from baseline at week 8.

Data from the STRATUM study also showed a statistically significant improvement with vehicle in all secondary endpoints, including itching, scaling, and erythema. More than 60% of patients achieved a 4-point reduction in itching at week 8 as measured by the Worst Itch-Numerical Rating Score (62.8% roflumilast foam vs. 40.6% vehicle; P=0.0001), and significant improvements in itching were also reported at week 2 and week 4. Patients treated with roflumilast foam reported a 28% improvement in itching from baseline at 48 hours (vs. at 13% on the vehicle’s nominal P=0.0024).

Roflumilast foam was well tolerated with a favorable safety and tolerability profile for up to 52 weeks of treatment. The Incidence of Treatment Emergent Adverse Events (TEAEs) was low and similar between active treatment and vehicle, with most TEAEs assessed as mild to moderate in severity. There were no treatment-related Serious Adverse Events (SAEs). Overall, the most common adverse reactions occurring in 1% of patients in the combined phase 2 and phase 3 study population were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).

About 10 million people in the United States have seborrheic dermatitis, but until now, there were limited treatment options. We are thrilled with this FDA approval and excited to bring to market a new, highly effective steroid-free topical formulation that can be used anywhere on the body. Our commercial team is ready and prepared to launch ZORYVE foam as soon as possible, and we are committed to ensuring affordable access to ZORYVE foam to those who can benefit from this novel treatment, said Frank Watanabe, the president and CEO of Arcutis, in a news release.1

This article originally appeared in Dermatology Times.

1. The FDA has approved Arcutis ZORYVE (roflumilast) topical foam, 0.3% for the treatment of seborrheic dermatitis in individuals aged 9 years and older. News release. Arcutis Biotherapeutics. December 15, 2023. Accessed December 15, 2023. seborrheic-dermatitis -in-individuals-aged-9-years-and-older/

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