Recent Developments

Consensus Paper: Systemic Treatment of Children with Inflammatory Skin Disease During Pandemic

Management of pediatric patients with inflammatory skin diseases can present clinical challenges, and the emergence of the COVID-19 pandemic had potential to complicate matters. In response to the emerging health crisis, new expert consensus guidance has been published in Pediatric Dermatology, the official journal of the Society for Pediatric Dermatology (SPD). Kelly M. Cordoro, MD of the Division of Pediatric Dermatology, University of California San Francisco School of Medicine, was the senior author of the paper, “Systemic Immunosuppressive Therapy for Inflammatory Skin Diseases in Children: Expert Consensus-Based Guidance for Clinical Decision-Making During the COVID-19 Pandemic.”

“Children are, in general, under-treated for systemic inflammatory skin diseases. There’s been— rightfully so—a concern about short- and long-term side effects of immunosuppression and immunomodulation on a growing and developing child. But we also recognize now more than ever, that there can be downstream consequences of uncontrolled systemic inflammation. And we see the proof of that in diseases like psoriasis, where young adults may have cardiac issues and other comorbidities,” asserts Dr. Cordoro. “We should no longer borrow data from adults and we should not undertreat children just because they are children. We certainly have to be careful and be very thoughtful about when to start a therapy and what therapy to start. It really depends on shared decision making between the provider and the family, and recognizing which children do require treatment. The pandemic calls for a heightened level of careful individualized decisions about management, but in and of itself is not a reason to withhold treatment.”

A survey that formed the basis of the guidance statement was deployed to pediatric dermatologists across the US and found that most planned to continue therapy for asymptomatic patients. However, patients on immunosuppressive medications who test positive for SARS-CoV-2 should temporarily discontinue systemic and biologic medications; systemic steroids may require tapering, the survey concludes.

Among respondents, 87 percent said they were pausing or reducing the frequency of lab monitoring for certain immunosuppressive medications.

The guidance addresses the subset of patients receiving immunosuppressive therapies for inflammatory skin diseases like atopic dermatitis and forms of psoriasis, not those with vascular and neoplastic diseases, Dr. Cordoro notes. Immunosuppressive therapies can be generally categorized as broad acting, like cyclosporine or methotrexate, or targeted, like TNF inhibitors or IL 12/23 inhibitors. Dr. Cordoro says the consensus paper generally adheres to these categorizations.

“There was not much known specifically about pediatric patients with inflammatory skin disease and on immune suppressive or modulating therapy and COVID-19 caused by the SARS-CoV-2 virus at the time of assembling this task force and developing these guidelines,” Dr. Cordoro says. “We were very early on in the course of the pandemic as it struck the US, so we had very little information to go by. What is most important about this work is that everybody agreed unanimously that much of these decisions are context dependent.” She explains that main questions were whether patients on treatment were at increased risk to contract COVID and, if so, if there may be specific consequences or comorbidities from immunosuppressive drugs. Conversely, are there risks associated with undertreating the existing inflammatory skin disease? “In discussions with colleagues around this work, we all agreed that medical decision making in this context requires a careful consideration and balance of the risks of infection, the underlying skin disease, the specific drug, the epidemiology of the pandemic, evidence, and patient risks and preferences.”

Assuming that patients undergoing treatment adhere to infection mitigating strategies, the surveyed physicians felt that there was no need for wholesale discontinuation of immunosuppressive therapies. The paper authors acknowledge that it is based on current information and that the situation is evolving. However, Dr. Cordoro says that, overall, the recommendations seem to be holding as new information emerges.

For example, Dr. Cordoro says that the statement notes that pretreatment SARS-CoV-2 PCR testing would be ideal, even though such testing was not available for asymptomatic patients at the time the guidelines were developed. “Now we do have more widespread testing for asymptomatic patients,” she says. “Just yesterday and again, today I’ve initiated systemic immunosuppressive therapy, one for a patient with severe linear scleroderma and one for severe generalized pustular psoriasis. In both of those cases, I was able to get a COVID PCR test to reassure myself that the patient was negative, whereas before we didn’t have access to that.”

Dr. Cordoro also notes that the Pediatric Dermatology COVID-19 Response Task Force has developed original educational content for patients and caregivers and resources for providers accessible via the Society for Pediatric Dermatology (pedsderm.net/) and Pediatric Dermatology Research Alliance (pedraresearch.org) websites. Further information is available at pedsderm.net/resources/general-information-for-patients-and-caregivers-about-covid-19.

Ortho Dermatologics Launches Arazlo Lotion

Bausch Health Companies Inc. and its dermatology business, Ortho Dermatologics launched Arazlo (tazarotene) Lotion, 0.045%. Now available commercially to health care professionals in the US, it was FDA approved in December 2019 as the first tazarotene acne treatment available in lotion formulation. Arazlo is Indicated for the topical treatment of acne vulgaris in patients nine years of age and older.

FDA Approves Keytruda for Recurrent or Metastatic cSCC

The FDA has approved Keytruda, Merck’s anti-PD-1 therapy, in both three- and six-week dosing options as monotherapy for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation. This approval is based on data from the Phase 2 KEYNOTE-629 trial, in which Keytruda demonstrated meaningful efficacy and durability of response, with an objective response rate (ORR) of 34 percent (95 percent CI, 25-44), including a complete response rate of four percent and a partial response rate of 31 percent. Among responding patients, 69 percent had ongoing responses of six months or longer. After a median follow-up time of 9.5 months, the median duration of response (DOR) had not been reached (range, 2.7 to 13.1+ months).

New Dupixent Pre-filled Pen Gets FDA Nod

The FDA has approved a 300mg single-dose pre-filled pen for Regeneron Pharmaceuticals, Inc. and Sanofi’s Dupixent (dupilumab). The pre-filled pen is approved for all Dupixent indications in patients aged 12 years and older, which includes use in certain patients with atopic dermatitis.

The 300mg pre-filled pen is expected to be available in the US in the third quarter of 2020. The pre-filled pen features a hidden needle and single-press auto-injection, along with visual and audio feedback to help with administration. Regeneron and Sanofi are working with the FDA to provide additional data they require to complete their review of the 200mg pre-filled pen. The pre-filled syringe continues to be available in both 200mg and 300mg doses for use in a clinic or at home by self-administration. Both methods of administration require training by a healthcare professional.

Juvéderm Voluma XC Approved for the Chin

The FDA has approved a new indication for Juvéderm Voluma XC for the augmentation of the chin region to improve the chin profile in adults over the age of 21. The Juvéderm Collection of Fillers has the broadest portfolio of specifically tailored treatment options, and this latest approval marks their fifth approved indication in the US, according to Allergan Aesthetics, an AbbVie company.

This approval marks the second indication for the product, which was previously approved by the FDA in 2013 for cheek augmentation to correct age-related mid-face volume deficit.

In the US pivotal study, Juvéderm Voluma XC was shown to be safe and effective for augmentation of the chin, with the majority of patients reporting high satisfaction throughout the 1-year follow-up.

Clascoterone Cream 1% Exhibits Long-Term Safety for Treatment of Acne

Cassiopea SpA’s Clascoterone cream 1% is safe for the treatment of acne with low rates of treatment-related adverse events, according to a study in the online issue of Journal of the American Academy of Dermatology (JAAD).

Clascoterone is a topical androgen receptor inhibitor that fights acne by limiting dihydrotestosterone binding to the androgen receptors in the sebaceous gland. The FDA is reviewing a New Drug Application for Clascoterone cream 1% with an expected PDUFA date of August 27, 2020.

Take 5: Soliton’s Wally Klemp

Patients treated with Soliton’s investigational Rapid Acoustic Pulse (RAP) device experienced an average 32.5 percent improvement in Cellulite Severity Score, according to newly released data presented by Elizabeth Tanzi, MD, Director at Capital Laser & Skin Care, Chevy Chase, MD, at the American Academy of Dermatology (AAD) 2020 VMX Virtual Conference.

Among 62 evaluable subjects in the pivotal cellulite clinical trial, 85 percent of subjects responded to treatment with the improvement in the Cellulite Severity Scores ranging from 6.7 percent to 85.7 percent.

Dr. Tanzi, a member of Soliton’s Scientific Advisory Board, notes that while existing therapies for cellulite provide some benefit, “there’s a lot of room for improvement.” She says the Soliton technology is, “exciting to me for a number of reasons. First, this was a single treatment. We need additional research to determine what happens after multiple treatments. Also, we need to investigate the best interval between treatments because what we are seeing is that clinical results seem to improve over time, which is the exact opposite from the non-invasive treatments that are on the market.”

Dr. Tanzi notes that, “The three independent evaluating physicians were able to correctly identify before and after photos about 85 percent of the time...I think that’s important, as well as the overall subject satisfaction. When asked if their cellulite appeared improved, approximately 92 percent of the subjects said they agreed or strongly agreed.”

Co-Founder and Executive Chairman of Soliton Wally Klemp recently spoke about the company and its novel technology.

1. The Technology is “Entirely New”

“We make the assertion that this is an entirely new form of acoustic pulse technology,” says Mr. Klemp. “Our mechanism of action is not only unique, but it has a range of potential applications.” The platform is cleared as an adjunct to 1064 Q-switch laser for tattoo removal. “With the new positive pivotal cellulite data, we’re well on our way with the cellulite indication and we’ve also recently reported positive results in a proof of concept trial for keloid and fibrotic scars.” Mr. Klemp and company co-founder and CEO, Dr. Chris Capelli, predict that those three indications offer in excess of $10 billion worth of total global market opportunity.

2. Pulse Speed Matters

Though the Soliton RAP technology shares some basic similarity to the familiar ZWave device, there are key differences, Mr. Klemp says. For example, the latter device pulses averages around a megapascal, the Soliton device is capable of hitting approximately 10 times that level of peak pressure. “That seems important, but it’s really not nearly as important as some of the other characteristics,” Mr. Klemp says. “We make our acoustic pulses essentially using electrohydraulics…the benefit is, not only are we capable of hitting much higher peak pressures, but more importantly, we can do this in a very short period of time, less than 100 nanoseconds compared to 25 microseconds. That speed is really important when we get down to mechanism of action.

“We all know this intuitively because we know sound travels faster through water than through air, for example. Well, the same holds true for dermatological structures. The septa in the skin that connect the dermis to the body fascia through subcutaneous fat are an important target. They’re responsible for the appearance of cellulite, for example. Those septa are denser and much stiffer than the surrounding subcutaneous fat cells. And when you have this much of a high-speed acoustic event, when it encounters a change in stiffness, in the stiffness of the medium that it’s traveling through, you get what are called shearing waves or shearing effects. So it’s the speed, not so much the peak pressure, that is responsible for this shearing effect.”

3. Consumables Serve a Purpose

The Soliton platform represents, “a razor and blade revenue model, where the handpiece has a removable and replaceable cartridge,” Mr. Klemp says. The cartridge is a “legitimate consumable. It is expended in the process of a typical office visit for a patient. And it has to be replaced because it literally wears out.”

4. Treatment is Comfortable

Treatment with the Soliton RAP technology is not associated with any significant pain. “We’re typically in our clinical trials sometimes zero, but on average, probably closer to two, to two and a half on a 10-point pain scale. Some patients can sleep through our procedure, it’s that innocuous,” Mr. Klemp says. “So, no anesthesia required. There are no adverse events, no bleeding, no bruising, no downtime whatsoever.”

5. “Hardcore Research” is at the Root

The Soliton RAP platform, “is part of what resulted from five years of hardcore research. And that first five years consumed $25 million worth of R&D spending,” Mr. Klemp says. “This was a monumental undertaking, and it’s brand new science.

“We believe our RAP technology offers a completely new and innovative approach for multiple aesthetic indications based on extensive clinical research in tattoo removal, cellulite reduction, keloid scarring reduction, among other potential future indications. We remain focused on executing our current US commercialization plans, adapted as a result of the ongoing COVID-19 pandemic, which now strategically incorporates both tattoo removal and cellulite treatment, if cleared by the FDA, into our Generation II RAP device.”

COVID Toes: Virtual Platform Identifies Trend

When his then girlfriend, a dermatologist, mentioned that she was beleaguered by requests for “curbside” consults in social settings, orthopedic surgeon Alexander Börve, MD started a research project that eventually led to the launch of FirstDerm, an on-demand teledermatology service. The app and web-service connects people with dermatology concerns directly to human dermatologists for answers—anywhere, anytime, anonymously. As the rate of COVID-19 infections increased across the globe, the FirstDerm team noted an increase in specific queries. “In April 2020 we started getting some strange looking toes, and they were mostly answered as fungus,” Dr. Borve says. “However when we did an audit and looked online, we saw reports from Italy and Spain that this was Chilblains and COVID-19 related, so we updated the answers in respect to that, and notified all our dermatologists to be aware of strange skin concerns, especially on toes and fingers. We also recommended our users to get a COVID-19 test, isolate, and read the latest information on CDC’s COVID-19 pages.”

According to Dr. Borve, the platform to date had received 24 cases of suspicious COVID-19 related skin diseases (See sample case image above). None complained about other symptoms. Roughly 80 percent were men; 20 percent women between the ages 14 to 36 years.

Dr. Borve believes that digital platforms like FirstDerm could be leveraged as tools for global disease surveillance. “We already see trends,” he says. “We can draw a conclusion with Chilblains and COVID-19. For example, last year we only had two Chilblain cases, this year in three months we have seen 24 cases. However, the volume is not big enough to draw any conclusions on other skin diseases. For example, in spring and summer time, we get more skin tumor concerns. An interesting observation that we discovered early on was the influx of genital questions. Even though we did not promote the service as an STI service, we had a lot of questions about STIs.”

Most requests to FirstDerm are from men (75 percent) and in the majority of cases the skin disease is benign, like Folliculitis, pearly penile papules, balanitis, and sebaceous glands. “However, 25 percent of those queries are diagnosed as an STI, like genital warts, genital herpes and syphilis, as well as molluscum contagiosum and suspected scabies.”

Dr. Borve answered some additional questions about the platform.

How can dermatologists get involved/benefit from this tool?

The platform is “store and forward”; like an “Uber” platform, a dermatologist picks a case they are comfortable answering on their own time. There are no back and forth answers; our support handles follow up questions. At the moment, we do not prescribe any medication. Seventy percent are recommended over the counter treatments and 30 percent are prioritized for a dermatologist visit. It takes our dermatologists on average two to five minutes answering a query. On average cases are answered within six hours. The kinds of cases we get are 45 percent inflammatory skin diseases, 25 percent questions about tumors, and 30 percent genital concerns. Particularly people that are worried about an STI. Before on boarding we do a short test that we need for insurance purposes and the dermatologists get a feel of what type of cases that come in. Dermatologists are compensated per answered case. Our dermatologists answer cases as an extra revenue source, however the feedback has been that they enjoy the sometimes challenging cases. It’s like gaming or “soduko” for dermatologists.

Some apps have raised concerns about patients trying to self-diagnose. Have you developed the tool with that in mind?

In the age of the internet, you cannot get away from patients self-diagnosing, or patients thinking they have the expertise of a dermatologist after searching the internet for three hours. Eighty percent search their medical condition; if you have a skin concern you would Google “red rash on arm,” then click the “image” tab and compare the images to your skin concern. Google has over the years used artificial intelligence to optimize the images presented in this tab and the quality of images representing a skin diagnosis is extremely good, so the layman can compare these images to their skin concern and then read more about it on the respective website. 90 percent of what our users ask us are on 43 skin diseases – the same diseases come in to our platform again and again. Our users use it for sudden skin rashes, skin cancer worries, and second opinions. We have had several patients that have not been correctly diagnosed by doctors and use our service out of frustration or they want to have a confirmation.

Over the years we have identified over 700 malignant melanoma and advised the user for an urgent dermatologist visit. Here are stories on two of my friends that have used it to get the melanoma diagnosis:

medium.com/@DrBorve/how-my-health-app-saved-an-entrepreneur-9048c53fd5e1

www.firstderm.com/alexander-borve-saved-his-best-friend-malignant-melanoma/

Low Risk of Antibiotic Resistance with Seysara

The FDA approved a label update for Almirall’s Seysara stating that C. acnes strains displayed a low propensity for the development of resistance to sarecycline. This information is included in the Microbiology Section (12.4) of the prescribing information.

New Tralokinumab AD DATA

LEO Pharma A/S shared results showing that tralokinumab 300mg, administered subcutaneously every two weeks, demonstrated efficacy and safety with or without concomitant use of a topical corticosteroid (TCS) in three Phase 3 trials (ECZTRA 1-3) for the treatment of adults with moderate to severe atopic dermatitis (AD) at the American Academy of Dermatology (AAD) Virtual Meeting Experience 2020.

Tralokinumab is a fully human monoclonal antibody that specifically neutralizes the IL-13 cytokine.

In all three trials, tralokinumab met its primary endpoints at week 16 as assessed by the Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and at least a 75 percent improvement in the Eczema Area and Severity Index score (EASI-75). Tralokinumab also demonstrated significant improvements in secondary endpoints, including the extent and severity of skin lesions, pruritus, and health-related quality of life measures at week 16, when administered once every two weeks with or without concomitant TCS use.

New Phase 3 Data for Tremfya

New long-term plaque psoriasis data for The Janssen Pharmaceutical Company’s Tremfya (guselkumab) show consistent, high levels of skin clearance at week 100 and week 204 (four years).

In the open-label extension of VOYAGE 2, at four years, 80 percent of patients who were treated with guselkumab 100mg every eight weeks (q8w), achieved at least 90 percent improvement in the Psoriasis Area and Severity Index (PASI 90) score. At four years, the proportion of patients who achieved an Investigator’s Global Assessment (IGA) score of clear (0) or minimal disease (1) was 82 percent, and 51 percent of patients achieved PASI 100, or complete clearance of their psoriasis plaques.

Separately, data from the Phase 3 VOYAGE 1 trial comparing patient-reported outcomes between those being treated with guselkumab and those being treated with adalimumab show that at week 48, approximately 42 percent of guselkumab-treated patients and 23 percent of adalimumab-treated patients were symptom-free, as demonstrated by a PSSD symptom score of 0, and 36 percent vs 19 percent, respectively, were sign-free, as demonstrated by a PSSD sign score of 0.

Bimekizumab Phase 3 Data

UCB shared first presentations of data from the Phase 3 clinical development program of bimekizumab, its investigational IL-17A and IL-17F inhibitor, as part of a virtual session for the American Academy of Dermatology (AAD) 2020 Annual Meeting. Patients treated with bimekizumab achieved superior skin clearance in both the BE VIVID and BE READY Phase 3 studies, compared to those who received placebo or ustekinumab (Stelara). The majority of bimekizumab-treated patients in both studies achieved total skin clearance at week 16 and maintained response for a year, as measured by the Psoriasis Area and Severity Index (PASI) 100 and Investigator Global Assessment (IGA) response of 0.

CLOSE UP with Emma Guttman-Yassky, MD, PhD

Hand eczema affects about 10 percent of the US population, according to the National Eczema Association, and symptoms such as redness, itching, pain, dryness, cracks, and blisters can dramatically impair quality of life. Unfortunately there is no excellent treatment option for hand eczema…yet. This is why Emma Guttman-Yassky, MD, PhD, the Sol and Clara Kest Professor of Dermatology, Vice Chair of the Department of Dermatology, Director of the Center for Excellence in Eczema and Director of the Laboratory of Inflammatory Skin Diseases in the Department of Dermatology at Icahn School of Medicine at Mount Sinai in New York, is enthused about the recently released topline results of a Phase 2b clinical trial looking at Asana’s oral JAK/SYK antagonist, gusacitinib, for hand eczema. Here, she discusses the promising findings and the crucial next steps.

WHY IS THIS TOPIC IMPORTANT TO STUDY?

Dr. Guttman-Yassky: Currently patients with chronic hand eczema do not have unique treatment, and patients are mainly treated with topical steroids. Further, patients with chronic hand eczema with moderate-to-severe disease that do not respond to topical steroids do not have approved systemic treatments that can benefit them once they failed topical treatments.

DESCRIBE THE RESEARCH AND YOUR FINDINGS.

Dr Guttman-Yassky: Asana’s drug is a JAK/SYK antagonist that targets several cytokine axes, including type 2, type 17 and type 1, and this is an important point as chronic hand eczema is a heterogenous disease that encompasses atopic dermatitis as well as allergic and irritant contact dermatitis. Thus, it is beneficial to be able to target several cytokine axes to control moderate-to-severe chronic hand eczema. The study was a randomized, double-blind, placebo-controlled, parallel-group study evaluating oral gusacitinib (40 mg or 80 mg once daily) for up to 32 weeks, with the primary endpoint of mean modified total lesion severity score (mTLSS) at week 16. Topline results show that gusacitinib achieved a dose-dependent, clinically meaningful, and statistically significant improvement relative to placebo in both the primary and key secondary endpoints of efficacy. Gusacitinib 80 mg resulted in an overall decrease of 69 percent (p<0.005) in mTLSS from baseline, compared to a 49 percent decrease for 40 mg and 33 percent decrease for placebo. Both 40 and 80 mg doses resulted in 50 percent and 66 percent improvement, respectively, in the mTLSS pruritus sub-score at week 16. Topline results also show significant improvement in key secondary measures such as Physician’s Global Assessment (PGA) with a 5-fold increase in subjects achieving clear or almost clear over placebo at 80 mg dose. Rapid and clinically relevant reductions in mTLSS (p<0.005), PGA (p<0.05) and pruritus were observed as early as 4 weeks and sustained for the duration of the study. Both doses of gusacitinib were well tolerated.

WHAT IS THE NEXT STEP?

Dr Guttman-Yassky: The next step is a Phase 3 study to get the drug approved. This drug will be the first approved systemic medication for patients with moderate to severe hand AD. It will provide a game change as up to now we did not have approved oral treatments for patients with severe chronic hand eczema. Further, some systemic treatments that are used off label are oral steroids and cyclosporin that are not feasible options for long-term use, emphasizing the huge need for safer treatment options for long-term use.

Burt’s Bees Natural Retinol Alternative Works Well in Sensitive Skin

New studies from Burt’s Bees were presented online at the American Academy of Dermatology (AAD) Virtual Meeting Experience (VMX) 2020.

In one study, treatment with a retinol alternative, bakuchiol, for four weeks showed statistically significant improvements in investigator-graded and subject-graded efficacy parameters; statistically significant improvements in efficacy parameters; statistically significant increase in skin hydration. There were no significant changes in skin barrier function and no significant tolerability issues

Overall, treatment with nature-based retinol alternative bakuchiol was effective and well-tolerated in improving overall skin condition of photo-damaged skin without any signs of irritation, the study authors reported.

In another study, treatment with a nature-based lip treatment containing botanicals for two weeks demonstrated statistically significant reduction in the appearance of fine lines, texture, scaling and dryness on lips and increase in lip hydration/ Overall, a nature-based lip treatment was effective and well-tolerated in improving the overall lip condition of subjects with moderately to severely dry lips, the study authors concluded.

In a third study from Burt’s Bees, a nature-based facial oil demonstrated antioxidant and photoprotective effects, as it showed significant reduction in oxidative stress following UVA radiation exposure and erythema following UVB radiation exposure.