Incyte’s Opzelura is First Topical JAK Inhibitor Approved in US
Opzelura (ruxolitinib) cream from Incyte is now the first and only topical formulation of a JAK inhibitor approved in the US. FDA approved Opzelura for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.
“Atopic dermatitis is a chronic immune-mediated disease that can be challenging to manage. Many patients do not respond well to existing treatments and have uncontrolled disease,” says Jonathan Silverberg, MD, PhD, MPH, Associate Professor of Dermatology and Director of Clinical Research and Contact Dermatitis at The George Washington University School of Medicine and Health Sciences. “As a clinician, I am excited to have a non-steroidal topical cream like Opzelura.”
Research shows dysregulation of the JAK-STAT pathway contributes to key features of AD such as itch, inflammation, and skin barrier dysfunction.
The FDA approval is based on data from the TRuE-AD (Topical Ruxolitinib Evaluation in Atopic Dermatitis) clinical trial program, consisting of two randomized, double-blind, vehicle-controlled Phase 3 studies (TRuE-AD1 and TRuE-AD 2) evaluating the safety and efficacy of Opzelura in more than 1,200 adolescents and adults with mild to moderate AD. Results from the studies show patients experienced significantly clearer skin and itch reduction when treated with Opzelura cream 1.5% twice daily (BID), compared to vehicle (non-medicated cream).
Lots of hope is pinned on Janus kinase (JAK) inhibitors for the treatment of AD, alopecia areata, vitiligo, plus other skin diseases, and the pipeline is full.
Will the recent FDA decision to expand the boxed warning for JAK inhibitors—citing risk for heart-related issues, cancer, and death—dampen some of this enthusiasm for this emerging class of medicines? Read DermWire Special Report: JAK Inhibitors in Dermatology by Denise Mann to learn what leading dermatologists think. Read the special report here.
Diagnostic Value of DermTech’s PLA
Evaluation of genomic atypia with DermTech’s Pigmented Lesion Assay (PLA) increases both the real-world negative predictive value (NPV) and positive predictive value (PPV) of the melanoma diagnostic pathway and reduces biopsy burden, relative to the current visual assessment and histopathology pathway, new data show. The research appears in SKIN: The Journal of Cutaneous Medicine.
Results of the study indicate that the non-invasive detection of genomic atypia by the PLA can complement visual assessment of pigmented lesions and enhance early detection of melanoma, enabling clinicians to triage suspicious lesions more effectively to determine which are high risk and should be biopsied versus safely managed via clinical surveillance.
The TRUST study was conducted in the US using a cohort of 2,575 PLA-tested lesions for evidence of melanoma detected during a protracted follow-up period of up to 36 months and by re-testing a subset of 302 PLA-negative lesions up to 24 months after the initial PLA test. Results demonstrate that in this real-world intended use population, the PLA has an NPV of greater than 99 percent, confirming the high NPV established in previous clinical studies.
Real-world PPV of 18.7 percent was determined by identifying melanoma diagnoses among PLA-positive lesions within a US-based registry of 3,418 PLA-tested cases. The PLA’s detection of genomic atypia enriched the pool of biopsied lesions nearly five-fold for those most likely to be diagnosed as high-risk or severely atypical and malignant.
Of the 5,993 lesions tested with the PLA (TRUST Study and registry cases), the vast majority of PLA tests were negative and not subjected to surgical biopsy.
Lexette Approved for Adolescents
Lexette (halobetasol propionate) foam, 0.05% from Mayne Pharma is now approved for the treatment of plaque psoriasis in patients aged 12 years and older.
FDA approved Lexette in 2018 for use in adults. Approval in adolescents is based on data obtained in an open label follow-on study to the inititial mulitcenter trials in adults. The follow-on studies involved patients aged 12 to 17 years of age with plaque psoriasis.
Nutrafol May Promote Hair Growth in Menopausal Women
Nutrafol may improve hair growth and quality for perimenopausal, menopausal, and postmenopausal women, according to research presented during The North American Menopause Society (NAMS) Annual Meeting in Washington, DC.
Researchers compared results at six and 12 months of treatment and found mean total hair counts increased significantly and progressively in perimenopausal, menopausal, and postmenopausal women. Global hair quality improvements significantly increased by 40 percent with few or no side effects, along with a decrease in hair shedding, the study found.
The study was funded by Nutrafol manufacturer Nutraceutical Wellness.
Take 5 with June Lee Risser
Lots of big, exciting changes are taking place at Galderma. To get the inside scoop, Practical Dermatology® magazine sat down with June Lee Risser, Vice President, and General Manager for the U.S. Galderma Consumer Care business. She is responsible for leading the US commercial organization for the Galderma portfolio of consumer-available brands including Cetaphil and Differin.
New Formulations for Hero Products
“We are an iconic and timeless brand, but that doesn’t mean we are not constantly changing, innovating, and modernizing our products. The brand’s most prominent products have been upgraded to feature a dermatologist-backed blend of niacinamide (Vitamin B3), panthenol (Vitamin B5), and hydrating glycerin to improve skin’s overall resilience. Gentle Skin Cleanser, Daily Facial Cleanser, Moisturizing Lotion, and Advanced Relief Lotion are now free of parabens, sulfates, and animal origin ingredients, and are not tested on animals at any stage. The reaction has been extremely positive so far. Fully 98 percent of consumers said the updated daily facial cleanser left their skin feeling balanced. Making sure that the science and clinical testing are rock solid before we launch including gathering input from the dermatology community is part of our mission.”
Smarter Packaging
“Cetaphil is also unveiling an updated logo and sleeker, more modern packaging that features color-coding for specific skin types, making the shopping experience easier for consumers. As part of the brand’s Clear Skies sustainability initiative, this also includes smarter packaging for products and cleaner formulas. Gentle Skin Cleanser, Daily Facial Cleanser, Moisturizing Lotion and Advanced Relief Lotion are now made with readily biodegradable formulas, with additional products to be reformulated in the future, and the products are housed in packaging that is in-part recyclable at most facilities. In addition to the new launches, the brand is also refreshing its marketing material with a digital-first approach. There are a lot of ways we are trying to reach the millennial consumer. We will have a big push around influencers including skinfluencers and health care influencers.”
Renewed Commitment to Sensitive Skin
“We are and have always been committed to sensitive skin. Seventy percent of women in the United States self-diagnose as having sensitive skin, but there is no formal medical definition for sensitive skin yet. Sensitive skin can run the gamut from dry skin in winter to a compromised skin barrier due to skin diseases such as atopic dermatitis or other skin conditions. At Galderma, we aim to address the five signs of sensitive skin: dryness, roughness, tightness, irritation, and weakened skin barrier. Our products aim to address this full spectrum of needs. Cetaphil is also calling March 22nd through March 28th Sensitive Skin Awareness Week.”
Biggest Launch Year Ever
“Cetaphil is launching 16 new products this year. This is the biggest number of new launches in one year in our 70-year history. Beginning the year with a launch into the sun care category with its Sheer Mineral Collection, the brand is rolling out five new products for problematic skin, including the Healing Ointment, Daily Smoothing Moisturizer for Rough & Bumpy Skin, Cracked Skin Repair Lotion, Cracked Skin Repair Balm, and Advanced Relief Cream with Shea Butter. Meanwhile, the brand also made its first-ever foray into acne care with its Gentle Clear Collection for sensitive, acne-prone skin and introduced a Healthy Radiance Collection to address dark spots and uneven skin tone without irritation. There are also some exciting new offerings at Differin including a scar treatment, an exfoliating cleanser, and an acne body care line to help address truncal acne.”
Diversity Push
“We are designing our products for a diverse consumer audience including skin, racial and ethnic, and age diversity. We have a passion for diversity and inclusion and advancing dermatology for every skin story.”
CLOSE UP with Emma Guttman-Yassky, MD, PhD
Few effective treatments are available for alopecia areata (AA) patients with extensive scalp hair loss, but recent evidence suggests that type 2 T-cell (Th2)-immune response may play a role in AA, similar to atopic conditions, such as atopic dermatitis (AD) and asthma.
Could dupilumab, a monoclonal antibody inhibiting Th2 signaling, help regrow hair?
That was the hypothesis driving a new study by Emma Guttman-Yassky, MD, PhD, the Sol and Clara Kest Professor and Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City.
And the answer seems to be a resounding yes. Dr. Guttman-Yassky spoke to Practical Dermatology® magazine about the study, which she called “one of the most exciting things I have ever done.”
Why Is this Topic Important to Study?
Emma Guttman-Yassky, MD, PhD: AA is devastating, and we don’t have good treatments to offer patients. Many patients with eczema/AD also have AA. In eczema, you think about the Th2 immune pathway, but we historically typically thought of AA as a Th1 driven disease. In fact, the connection to eczema led me look more deeply into this, researching scalp and blood samples of a large number of AA patients. It turns out that AA is very similar to AD in the sense that there is Th2 activation, that is also associated with AA severity. I also noticed that my patients with mild AA who were on dupilumab to treat AD regrew hair, so we also had a rationale for this study.
Describe the Research and Your Findings
Dr. Guttman-Yassky: AA patients with and without concomitant AD were randomized 2:1 to receive weekly subcutaneous dupilumab (300mg) or placebo for 24 weeks, followed by another 24-week dupilumab open-label phase. We gave injections weekly because we really wanted to give the maximum dose.
The primary outcome was a change from baseline in the Severity of Alopecia Tool (SALT) score at week 24. Secondary outcomes included a range of measures of hair regrowth. At week 24, disease worsening was documented in the placebo arm. After 48 weeks of dupilumab treatment, 32.5 percent, 22.5 percent, and 15 percent of patients achieved SALT30/SALT50/SALT75 improvement, respectively, while in patients with baseline IgE ≥ 200 IU/ml response rates increased to 53.8 percent, 46.2 percent, and 38.5 percent, respectively. Baseline IgE predicts treatment response with 83 percent accuracy. Patient selection based on baseline serum IgE levels may improve treatment results.
What is the Next Step?
Dr. Guttman-Yassky: I am hoping to follow up with a larger study, particularly in patients with personal or familial atopy or high IgE, and that this will become a treatment for AA. It’s such a safe treatment.
CLARIFICATIONS
Please note these clarifications from the September 2021 edition, available online at PracticalDermatology.com
- In the article “Optimizing Skin Exams with a Next-Gen Wireless Handheld Dermoscopy Solution” the captions for Figures 13 and 14 were transposed. They are placed correctly here.
- The article “New Tech Marries Data with Dermatology” compared the Mindera technology to that from DermTech. The two technologies are distinct. DermTech’s PLA uses RT-PCR to measure the gene expression of two genes, LINC00518 (long- intergenic non-coding RNA 00518) and PRAME (preferentially expressed antigen in melanoma) and identify the malignant changes of melanoma on the genomic level.
