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Arcutis Submits NDA for Roflumilast Cream 0.15% for AD Treatment

Arcutis Biotherapeutics, Inc. submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for roflumilast cream 0.15% for the treatment of mild-to-moderate atopic dermatitis (AD) in adults and children ages six years and older. This marks Arcutis’ third topical roflumilast NDA submission in two years.

Roflumilast cream is a once-daily, steroid-free, topical formulation of a highly potent and selective phosphodiesterase-4 (PDE4) inhibitor. It is formulated with HydroARQ Technology as a non-greasy emollient cream that absorbs quickly and does not disrupt the skin barrier. In addition, roflumilast cream does not include sensitizing excipients or irritants, such as propylene glycol, polyethylene glycol, isopropyl alcohol, ethanol, or fragrances.

The sNDA submission is supported by positive results from the “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis” (INTEGUMENT-1 and INTEGUMENT-2) trials; two identical Phase 3, parallel group, double-blind, vehicle-controlled trials in which roflumilast cream 0.15% or vehicle was applied once-daily for four weeks to individuals six years of age and older with mild to moderate AD involving ≥3% body surface area.

Both studies met the primary endpoint of IGA Success, defined as a validated Investigator Global Assessment – Atopic Dermatitis (vIGA-AD) score of "clear" or "almost clear" plus a 2-grade improvement from baseline at Week 4 (INTEGUMENT-1: 32.0% roflumilast cream vs. 15.2% vehicle, P<0.0001; INTEGUMENT-2: 28.9% roflumilast cream vs. 12.0% vehicle, P<0.0001).

More than 30% of individuals treated with roflumilast cream in each study achieved Worst Itch-Numeric Rating Scale (WI-NRS) Success at Week 4. WI-NRS Success is defined as achievement of at least a 4-point reduction on the WI-NRS 0-10 scale (in individuals 12 and older who had a baseline WI-NRS score of at least 4). Rapid and significant improvement in itch was observed in individuals treated with roflumilast cream compared with vehicle as early as 24 hours following the first application, as measured by the least-squares (LS) mean change from baseline in daily WI-NRS scores between the two groups (nominal P<0.05).

In both studies, approximately 40% of children and adults treated with roflumilast cream achieved a vIGA-AD score of Clear (0) or Almost Clear (1) at Week 4 (INTEGUMENT-1: 41.5% vs. 25.2%, P<0.0001; INTEGUMENT-2: 39% vs. 16.9%, P<0.0001), with significant improvement as early as Week 1 (P< 0.0001).

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 to vehicle (INTEGUMENT-1: 43.2% vs. 22.0%, P<0.0001; INTEGUMENT-2: 42.0% vs. 19.7%, P<0.0001). Significant improvements in EASI-75 were observed with roflumilast cream as early as Week 1 in both studies (nominal P=0.0006; nominal P=0.0329).

Roflumilast cream 0.15% was well tolerated. The incidence of Treatment Emergent Adverse Events (TEAEs) was low in both active treatment and vehicle arms, with most TEAEs assessed as mild to moderate in severity. 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 (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%).

The submission is also supported by data from a Phase 2 dose ranging study, an open label extension study in which patients were treated for up to 52 weeks, and two Phase 1 pharmacokinetic studies.


New Surgical Technique Offers Hope to Folliculitis Decalvans Patients

The lack of long-term solutions in the challenging treatment of folliculitis decalvans (FD) led Sanusi Umar MD, and colleagues from Dr. U Hair and Skin Clinic to develop and patent a novel device that holds potential for sustained FD remission.

Dubbed the Athena Suture Guards, the device is a high-tension suture guard that guides wound contraction and minimizes tissue damage during surgical excision.

A clinical study of five patients, including four men and one woman who had failed various conventional treatments, found that all patients experienced complete remission, with no instances of disease recurrence noted during the 10–24-month follow-up period.

The study is published in the Clinical Cosmetic and Investigational Dermatology Journal.

Though rare, FD resists conventional treatments and remains a major source of frustration and suffering for affected patients. Dr. Umar, the study’s lead author, attributes the teams’ results to the novel method of closing excision wounds with guarded high-tension sutures and using second-intention healing. Dr. Umar hopes that the five FD patients’ outcomes will encourage broader research to validate the research teams’ approach.

Biosimilar News: Samsung Bioepis, Sandoz to Develop SB17, a Proposed Stelara Biosimilar to Stelara

Samsung Bioepis Co., Ltd. has entered into a commercialization agreement with Sandoz for SB17, a proposed biosimilar to Stelara (ustekinumab).

Samsung Bioepis will be responsible for development, regulatory registration and manufacture and supply of the product in the United States (US), Canada, European Economic Area (EEA), Switzerland and United Kingdom (UK), and Sandoz will be responsible for commercialization in these regions.

SB17, a proposed biosimilar to Stelara (ustekinumab), is Samsung Bioepis’ fourth candidate in the immunology pipeline. SB17 Phase 3 clinical study results are set to be presented at a medical congress later this year.

In March, the company presented Phase 1 clinical study results of SB17 at the 2023 American Academy of Dermatology Annual Meeting. The study demonstrated pharmacokinetics (PK) equivalence and comparable safety, tolerability, and immunogenicity profiles between SB17 and reference ustekinumab.

Arcutis’ Roflumilast Cream 0.15% Performs Well in AD

Roflumilast cream 0.15% showed durable and improved efficacy over time and a favorable safety profile in mild to moderate Atopic Dermatitis (AD), according to interim results from the INTEGUMENT-OLE long-term open-label study.

Arcutis intends to submit a supplemental New Drug Application (sNDA) late in the third quarter of 2023 for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis in individuals ages 6 years and older.

Fully 46.1% and 51.0% of patients who rolled over from the roflumilast cream treatment arm in INTEGUMENT-1 or -2 achieved Investigator Global Assessment-Atopic Dermatitis (vIGA-AD) success, defined as vIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, at weeks 28 and 56, respectively. In addition, Roflumilast cream maintained disease control even when participants switched to twice weekly maintenance dosing schedule. Long-term safety and tolerability profile was consistent with short-term data in AD, with no new safety signals observed during 56 weeks of treatment, Arcutis reports.

Starting at week four of INTEGUMENT-OLE, participants who achieved a vIGA-AD score of clear (0) switched to twice weekly maintenance dosing. Participants were to resume once-daily dosing if vIGA-AD reached mild (2) or if signs or symptoms were not adequately controlled. More than two-thirds of participants who switched to maintenance dosing remained on the twice weekly schedule for more than half of their time in the study (post-Week 4).

Additionally, in the study, 61.5% and 66.2% of participants who rolled over from the roflumilast cream arm in INTEGUMENT-1 or -2 demonstrated a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) after 28 weeks and 56 weeks, respectively.

The long-term study results reinforce the safety profile of roflumilast cream already seen in the short-term INTEGUMENT-1 and INTEGUMENT-2 clinical trials, with no new safety signals observed up to 56 weeks. Overall incidence of adverse events was low, with most being mild to moderate in nature. The most frequently reported adverse events (≥2%) included: COVID-19, upper respiratory tract infection, nasopharyngitis, and headache. Overall, only 3.0% of trial participants discontinued the study due to adverse events.

Tarsus Rolls Out XDEMVY for Demodex Blepharitis

Tarsus Pharmaceuticals, Inc. is rolling out XDEMVY, the First and Only US Food and Drug Administration-approved treatment for Demodex blepharitis.

XDEMVY is now available at pharmacies nationwide for prescription.

Bobak Azamian, MD, PhD, Chief Executive Officer, and Chairman, rang the closing bell at the Nasdaq Stock Market on Sept. 6, 2023 to mark the launch.

Blepharitis is a common lid margin disease that is characterized by eyelid margin inflammation, redness, and ocular irritation. XDEMVY (lotilaner ophthalmic solution) 0.25%, formerly known as TP-03, is a novel prescription eye drop designed to treat Demodex blepharitis by targeting and eradicating the Demodex mite infestation.

The company is also developing forms of lotilaner to potentially treat rosacea, Lyme disease, and meibomian gland dysfunction.

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