PracticalDermatology

Just shy of 80 percent of women age 40 and older wish they could change the way their hands look, according to Nestlé Skin Health’s “Face Your Hands” survey.

Additionally, 60 percent reported they have taken steps to hide their hands because they are self-conscious about the way they look, and nearly two in three women are interested in having a non-surgical cosmetic procedure or treatment to improve the appearance of their hands, the survey showed.

Restylane Lyft is the first and only hyaluronic acid (HA) dermal filler FDA-approved for both helping to reverse the signs of volume loss in aging hands, as well smoothing facial wrinkles and folds. Merz’s Radiesse, which is comprised of calcium hydroxylapatite microspheres, is also FDA-approved for adding volume to the back of the hands.

The nationally representative survey was conducted by Wakefield Research among 1,000 US women, ages 35+ between February 26 and March 5, 2018 using an e-mail invitation and an online survey. Data were resported specifically for women age 40 and older. “Over time, the skin on the hands loses volume, which can result in a less youthful appearance,” says Joel L. Cohen, MD, a Lone Tree, CO-based dermatologist and clinical trial investigator for Restylane Lyft for the hands, in a news release. “I find that while many women spend time perfecting their facial beauty routine, they tend to forget about their hands. I am excited that there is now a hyaluronic acid-based treatment available to treat and help restore volume to the back of the hands, which is a problem area for many of my patients.”

Results suggest an opportunity for cosmetic dermatologists. Many women want to change the appearance of their hands, but most (54 percent) respondents believed nothing could be done to prevent signs of aging on their hands.

Almirall to Acquire Allergan’s US Medical Dermatology Unit

Almirall is acquiring a portfolio of five products from Allergan’s Medical Dermatology unit in the US, conditional to clearance by relevant authorities. The portfolio includes Aczone (dapsone), Tazorac (tazarotene), Azelex (azelaic acid), and Cordran Tape (fludroxycortide), as well as Seysara (sarecycline), a new first in class tetracycline-derived antibiotic with anti-inflammatory properties intended for the treatment of moderate to severe acne vulgaris, in patients nine years of age and older, with a best-in-class safety profile. FDA approval of Seysara (sarecycline) is anticipated in the fourth quarter of 2018.

The acquisition has been announced for a cash consideration of $550 million at closing. The Allergan portfolio had net sales of $70 million in the first half of 2018. Almirall expects peak sales of Seysara (sarecycline) from $150 to $200 million.

“This is a transformational deal for Almirall,” commented Peter Guenter, Almirall’s Chief Executive Officer. “It will reinforce and consolidate our position in the world’s largest dermatology market and is a well-balanced portfolio of mature and growth brands with a major launch opportunity of an innovative New Chemical Entity (NCE). It is perfectly complementary to our existing platform and will be immediately accretive to our earnings. It offers us medium to long term top and bottom line growth opportunities. Moreover, it will allow for an expanded platform to launch KX2-391, which has the potential to become a new standard of care in actinic keratosis.”

With this acquisition, Almirall says it consolidates and reinforces its presence in the US, the largest market in the world, and expands its range of dermatologic products, representing a transformational step for Almirall US as well as Almirall as a whole.

Bonti’s Neurotoxin Shines in Study of Scar Reduction After Mohs Surgery

Topline results from Bonti’s SHINE-1 Phase 2a clinical trial suggest that its novel neurotoxin is safe and likely effective for scar reduction following Mohs surgery.

In the trial, EB-001A or placebo was administered to the frontalis muscle immediately after Mohs surgery for skin lesions in the forehead in 12 subjects (eight active, four placebo) who were followed up to 90 days. EB-001A was well tolerated with no drug-related adverse events. EB-001A appeared to provide maximum benefit during the acute scar formation phase as the surgical wounds healed. Numerical improvements in clinical investigator-reported results and in key patient-reported outcomes suggest EB-001A may improve the wound healing process. Results include:

• Improvement in Scar Appearance: Based on Visual Analog Scale (VAS) scores by the investigator on Day 30, EB-001A-treated scars were about 50 percent better in appearance compared to scars in placebo subjects.
• Less Itching: 24 hours post-surgery, none of the EB-001A treated subjects reported itching, compared to 75 percent of placebo subjects who reported itching in the same timeframe.
• Less Pain: At 24 hours and eight days post-surgery, the majority of placebo subjects reported pain, while a smaller percentage of EB-001A treated subjects reported pain in the same timeframes.
• Improvement in Scar Characteristics: EB-001A-treated subjects showed improvements in patient-reported scar color and stiffness, as compared to the placebo group.

DecisionDx-Melanoma Test Improved Risk Prediction for Melanoma Recurrence, Metastasis

Castle Biosciences, Inc’s DecisionDx-Melanoma test improved risk prediction beyond that using American Joint Committee on Cancer (AJCC) based staging, according to a new study presented at the DERM2018 NP/PA CME Conference held in Las Vegas.

The study assessed the impact on risk assessment for patients with Stage I-III melanoma when including results from the DecisionDx-Melanoma test along with population-based AJCC staging in a 690-patient cohort.

The DecisionDx-Melanoma test uses tumor biology to provide an individual risk assessment for patients with melanoma. Results from this analysis showed that the addition of the test result to clinicopathologic AJCC staging significantly improved risk stratification. Technical reliability in over 17,000 clinical test orders was also assessed, and showed 98.3 percent reporting success for samples with adequate tumor content.

Multivariate analysis demonstrated that the Class 2B result was an independent predictor of melanoma-specific survival (MSS) with a greater hazard ratio than using AJCC staging alone to determine risk.

Results from this multicenter study in 690 patients with Stage I-III melanoma show that the addition of DecisionDx-Melanoma testing can significantly improve risk prediction based on AJCC 8th edition staging alone, and can better inform patient management decision-making.

The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including 702 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

LEO Pharma to Acquire Bayer Prescription Dermatology Business

LEO Pharma has entered into a definitive agreement to buy Bayer’s global prescription dermatology unit. The portfolio to be acquired includes branded topical prescription treatments for acne, fungal skin infections, and rosacea and a range of topical steroids with an annual turnover in 2017 of more than 280 million euros. It will enable LEO to expand significantly in key markets worldwide and broaden its therapeutic areas.

Bayer’s global medical dermatology portfolio, which includes prescription treatment solutions for acne (Skinoren), fungal skin infections (Travogen and Travocort), and rosacea (Finacea), and a range of topical steroids (Advantan, Nerisona, and Desonate), will add complementary treatment areas and strengthen the existing business of LEO Pharma worldwide, allowing the company to more than double sales in some markets, LEO says. The transaction does not include Bayer’s over-the-counter dermatology portfolio of brands such as Bepanthen and Canesten amongst others.

LEO Pharma will acquire the global product rights, except for Afghanistan and Pakistan, and take over the sales and marketing organizations in 14 countries, as well as a factory in Segrate, Italy. Around 450 people will join LEO Pharma as part of this transaction. The combination of the local sales and marketing organizations will make LEO Pharma more efficient.

Consensus: Straight-Line Vector Planning Produces Best Silhouette InstaLift Results

Straight-line vector planning produces the ideal lifting effect and sets the stage for maximum collagen regeneration with the Silhouette InstaLift, according to a study in the July 2018 issue of Journal of Drugs in Dermatology.

Silhouette InstaLift (Sinclair) uses resorbable suspension sutures with bi-directional cones to redefine the contours of the midface. The sutures lift and reposition tissue while the cones anchor the suture and facial skin in an elevated position. The sutures are absorbed over time, but the sutures and cones, made of glycolide/L-lactide (PLGA), stimulate fibroblasts for gradual collagen maturation (neocollagenesis). With this dual mechanism of action, Silhouette InstaLift delivers an immediate lift followed by an ongoing volumizing effect that improves with time.

Drawing on their collective experience treating more than 500 men and women with Silhouette InstaLift, researchers led by Z. Paul Lorenc, MD point out that sutures should be placed in a straight line that is perpendicular to the skin that requires lifting in order to maximize the mechanical lift and anchoring. If the goal is to lift the nasolabial folds, the sutures must be placed perpendicular to the lower part of the fold near the mouth for the most efficient pull on the tissues. The cones serve to anchor the sutures into this position.

When the procedure is performed correctly and in the right individual, Silhouette InstaLift results can last 18 to 24 months. While the physical lifting capacity of the suture declines as it is absorbed, the complementary collagen-stimulating properties provide ongoing revolumization, Dr. Lorenc says.

Experimental Drug May Reverse Hair Loss, Hair Whitening, and Skin Inflammation

An experimental drug can successfully reverse hair loss, hair whitening, and skin inflammation linked by previous studies to human diets heavy in fat and cholesterol, according to a new Johns Hopkins study in mice.

Investigators say the compound halts production of glycosphingolipids (GSLs), major components of skin and other cell membranes. Current research shows that mice fed a diet high in fat and cholesterol are more likely to have hair discoloration from black to gray to white, extensive hair loss and inflammation of skin exhibited by multiple wounds. Feeding these mice the compound appears to reverse such symptoms.

The Hopkins investigators caution that such results in mice do not mean that the same effects would occur in people, and there is no evidence at this time that the compounds they used would be safe in people. But the findings, they say, do shed light on possible pathways for addressing hair loss and skin wounds in humans with oral or topical medications.

A report on the findings was published in Scientific Reports.

AAD: Research Shows Free Skin Cancer Screenings Can Save Lives

Data indicate that the American Academy of Dermatology’s (AAD’s) SPOTme program serves an important need.

While skin cancer can be deadly, it is also highly treatable when detected early. In fact, melanoma, the deadliest form of skin cancer, has a five-year survival rate of 95 percent when detected and treated before it spreads to the lymph nodes; conversely, the five-year survival rates for regional and distant stage melanomas are 64 percent and 23 percent, respectively.

For more than 30 years, board-certified dermatologists have been providing free skin cancer screenings in their communities through the AAD’s SPOTme program—and new research, published in Journal of the American Academy of Dermatology, highlights the value of that program.

“In analyzing survey data collected from 1.8 million SPOTme screening participants over the course of 30 years, we learned that the program serves an unmet need for many of those participants,” says study author Hensin Tsao, MD, FAAD, a board-certified dermatologist and professor of dermatology at Harvard Medical School in Boston. “Our findings indicate that SPOTme® screenings have facilitated the detection of suspected skin cancers in high-risk patients, and that many of these lesions may have otherwise gone undetected.”

According to the study:

• 72 percent of SPOTme screening participants in 2009 and 2010 had a high risk for melanoma.
• 75 percent of those who received a suspected diagnosis of melanoma at a SPOTme screening in 2009 and 2010 fell into this high-risk category.
• 48 percent of those diagnosed with a suspected melanoma at a SPOTme screening from 2001-2010 indicated a doctor had never checked them for skin cancer.
• 83 percent of SPOTme screening participants diagnosed with a suspected melanoma from 1992-2010 indicated they did not have a regular dermatologist.
• 77 percent of SPOTme screening participants diagnosed with a suspected melanoma from 1992-2010 said they had not been to a previous skin cancer screening.
• 47 percent of participants diagnosed with a suspected melanoma from 1992-2010 said they would not have gotten a skin exam without the SPOTme program.

Almirall: Phase 3 Studies of KX2-391 for AK Meet Primary Endpoints

Two Phase 3 studies of KX2-391 met the primary endpoint of complete clearance of actinic keratosis (AK) lesions within the face or scalp treatment areas at day 57, Almirall, SA reports. Each study achieved statistical significance on this endpoint.

The double-blind, randomized, vehicle-controlled, studies were designed as pivotal phase III efficacy and safety studies to support the registration of KX2-391 (or KX-01) as field therapy for AK of the face and scalp. The studies, each conducted in 31 centers in the USA, enrolled a total of 702 patients. KX2-391 or vehicle ointment was applied once daily for five days. In addition to the clinical activity of KX2-391, the local skin reaction (LSR) profile was in line with the prior Phase 2 study results reported in the annual American Academy of Dermatology (AAD), meeting in February 2018 in San Diego.

Almirall and Athenex entered into a strategic partnership in December 2017 to further develop and commercialize KX2-391 for the treatment of actinic keratosis and other skin conditions in the United States and Europe, including Russia. Athenex is responsible for conducting all preclinical and clinical studies up to FDA approval. Almirall will employ its expertise to support the development in Europe and also to commercialize the product in the licensed territories.

Can Turning Off a Mutation Causing Wrinkling and Hair Loss Reverse the Processes?

A new mouse model suggests scientists may one day be able to reverse age-associated wrinkles and hair loss.

When a mutation leading to mitochondrial dysfunction is induced, the mouse develops wrinkled skin and extensive, visible hair loss in a matter of weeks, but when the mitochondrial function is restored by turning off the gene responsible for mitochondrial dysfunction, the mouse returns to smooth skin and thick fur, indistinguishable from a healthy mouse of the same age, report Keshav Singh, PhD, and colleagues at the University of Alabama at Birmingham.

“To our knowledge, this observation is unprecedented,” says Dr. Singh, a professor of genetics in the UAB School of Medicine in a news release.

The mouse in the center photo shows aging-associated skin wrinkles and hair loss after two months of mitochondrial DNA depletion. That same mouse, right, shows reversal of wrinkles and hair loss one month later, after mitochondrial DNA replication was resumed. The mouse on the left is a normal control, for comparison.

The mutation that does this is in a nuclear gene affecting mitochondrial function, the tiny organelles known as the powerhouses of the cells. Numerous mitochondria in cells produce 90 percent of the chemical energy cells need to survive.

In humans, a decline in mitochondrial function is seen during aging, and mitochondrial dysfunction can drive age-related diseases. A depletion of the DNA in mitochondria is also implicated in human mitochondrial diseases, cardiovascular disease, diabetes, age-associated neurological disorders and cancer.

“This mouse model,” Dr. Singh says, “should provide an unprecedented opportunity for the development of preventive and therapeutic drug development strategies to augment the mitochondrial functions for the treatment of aging-associated skin and hair pathology and other human diseases in which mitochondrial dysfunction plays a significant role.”

BPX-01: FDA Grants CARC Waiver; Post-Hoc Analysis Complete

The FDA has waived its requirement for a dermal carcinogenicity study for BPX-01 from BioPharmX Corporation, eliminating several years of non-clinical research normally required for FDA review.

BPX-01, a novel topical gel formulation of minocycline for the treatment of inflammatory acne, received the waiver based on the results of a 39-week dermal minipig toxicity study conducted by BioPharmX and the extensive safety history of minocycline products, including the clinical safety data from the BPX-01 Phase 2 acne studies. The 39-week minipig study with BPX-01 found no pre-neoplastic or hyperplastic changes that might be indicative of carcinogenic potential and the clinical studies were also negative in terms of cutaneous toxicity. Based on these data, FDA agreed that no new useful information was likely to be gained by additional non-clinical animal studies.

BioPharmX also has released a post hoc analysis of Phase 2b data assessing the impact of BPX-01 on the treatment of acne vulgaris in women. It found that female subjects outperformed the overall study population in the Investigator Global Assessment (IGA) outcomes.

The Phase 2b clinical trial (ITT=219) was a 12-week randomized, double-blind, vehicle-controlled, dose-ranging study to assess the safety and efficacy of BPX-01 minocycline topical gel in the treatment of moderate to severe inflammatory acne vulgaris. Relative to the total ITT population, a higher proportion of subjects in the female subgroup (N=149) demonstrated a clinically relevant improvement in acne severity. In female subjects with a baseline IGA score of 3 or 4 (moderate-to-severe), 29.2% achieved a two-grade reduction to clear or almost clear while 25 percent of the total ITT population achieved this reduction. In female subjects with a baseline IGA score of 3 (moderate only), 31.8 percent achieved a two-grade reduction to clear or almost clear.

The analysis was presented at the Dermatology Education Foundation’s DERM2018 conference in a poster.

Colorescience Receives Patent for Even Up Formulation

The US Patent and Trademark Office (USPTO) has granted a patent for Colorescience’s LUMIRA formulation, a clinically tested, highly effective complex that addresses the appearance of skin discoloration, found in the 3-in-1 treatment product, Even Up®Clinical Pigment Perfector.

The now patented (US Patent No. 9,956,163) formulation found in Even Up Clinical Pigment Perfector offers users three-in-one skincare benefits of SPF 50 all mineral protection, immediate color correction benefits, and ingredients that address the pigmentation pathway in the long term.

Summer AAD Highlights from DermWire TV

At the recent Summer meeting of the American Academy of Dermatology in Chicago, several presenters spoke to DermWire TV, offering highlights from their sessions. Practical Dermatology® Chief Medical Editor Neal Bhatia, MD says, “We talked about advanced systemic therapeutics in the session I ran with extraordinary colleagues covering all elements of using systemic drugs, basically taking some of the fears out of the dermatologists’ minds when treating patient not only organically but keeping dermatology on a high level.”

Watch the full episode for more from Dr. Bhatia, Todd Schlesinger, MD, and Seemal R. Desai, MD: bit.ly/DWTVAAD.

Skin Cancer Foundation Accepting Grant Applications

The Skin Cancer Foundation is now accepting applications for support of pilot research projects related to skin cancer. Two grants of $50,000 and one grant of $25,000 will be awarded. Researchers are invited to submit applications for one-year projects to be conducted within the dermatology departments of medical institutions in the US and Canada.

The application deadline is Friday, November 1, 2018. Questions may be directed to research@skincancer.org.

Promising Data for Fourth Generation Retinoid

New research in the British Journal of Dermatology reveals that trifarotene, a fourth-generation retinoid with potent and selective activity against only one particular retinoic acid receptor, may have an improved efficacy and safety profile compared with less selective retinoids.

Trifarotene is expected to result in low systemic levels, while retaining strong activity at the skin. This is likely to lead to reduced side effects.