2020 In Review

2020 will for certain be a year that lives in infamy. No longer simply a measure of time, “2020” has come to be shorthand for challenge, tumult, and uncertainty. The year has brought unprecedented challenges for Americans. And yet, even as many have suffered, medical practice has progressed. Ahead, we take a look at some of the top developments of the year.

PREDICTING—AND RESPONDING—TO COVID-19

As the COVID-19 pandemic was spreading into Europe in March, Bobby Buka, MD, JD of The Dermatology Specialists in New York City urged dermatologists to be vigilant for skin signs of the novel coronavirus. Since he spoke to DermWireTV in the spring, health officials have provided documentation of cutaneous manifestations of the disease, ranging from exanthema to “COVID toes.”

Writing in Journal of the European Academy of Dermatology and Venereology in April, Italian researchers reported on skin findings in 148 COVID-19 patients at the Lecco Hospital in Lombardy, Italy. They found that 20.5 percent of patients developed skin manifestations, among whom 44 percent had skin eruptions at symptom onset. Moreover, 78 percent had red rashes and three had widespread urticaria, typically on the trunk. Skin manifestations did not correlate with disease severity.

“COVID-19 is one devastating and recent example of the skin as window to the body’s extensive immune response,” Dr. Buka says now. “We’ve discovered that the cytokine storm in response to this pathogen is ultimately more destructive to parenchymal tissue than the virus itself! That’s fascinating. Managing inflammatory mediators is a core feature of dermatology. It is incumbent upon our specialty to identify cutaneous clues early, so that we serve an integral part of the nation’s early recognition and public health response.”

According to a late-breaking abstract presented at the 29th EADV Virtual Congress, some COVID-19 patients experience long-lasting cutaneous symptoms that vary according to the type of COVID-19 skin rash.

The analysis of the largest registry of COVID-19 patients with dermatological symptoms found that a subset of patients, called “long-haulers” or “long COVID,” experience prolonged symptoms (lasting >60 days) on their skin.

Data from 990 cases from 39 countries input into the registry, a collaboration between the International League of Dermatological Societies and the American Academy of Dermatology, show an average duration of 12 days for all dermatological symptoms, with some lasting 150 days or more.

Patients presented with a broad spectrum of dermatologic manifestations lasting different lengths of time, including urticaria lasting for median five days, and pernio/chilblains (‘‘COVID toes’’) lasting 15 days but sometimes as long as 130-150 days, and papulosquamous eruptions persisting for 20 days.

Shutdowns and other restrictions have impacted patient volumes and physician incomes. Eighty-one percent of physicians say their revenue is lower than it was in February, and one in five physicians has seen revenue reductions of 50 percent or greater, according to results of the American Medical Association’s COVID-19 Physician Practice Financial Impact Survey.

Similarly, more than one in five physicians have seen total patient visits reduced by half or more, even with expansion of telehealth. Almost seven out of 10 physicians are providing fewer total visits (in-person + telehealth), compared to February.

Doximity’s fourth annual Physician Compensation Report, which reflected the impact of COVID-19 office closures, shows physicians had relatively stagnant income. Nationwide, physicians saw a modest 1.5 percent average increase in compensation from 2019 to 2020. However, compared to the inflation rate of 2.3 percent, most physicians saw a decline in real income. Dermatology is the 13th highest paid specialty, with average compensation of $449,494.

The survey, based on responses from 44,000 US doctors, finds the gender wage gap was 28 percent this year—an increase from 25.5 percent last year. Overall, female doctors currently earn on average $116,289 less than their male counterparts.

Peter Alperin, MD, Vice President at Doximity, says that the gender pay gap in dermatology mirrors the overall gender pay gap in medicine.

“While the study wasn’t designed to look for causation, we suspect that that was largely because of all the usual issues that have been applying across the board for all professions and workers, which was that women tend to be more responsible for the family unit and therefore were asked or for whatever reason were sacrificing more for their family than men seem to be,” Dr. Alperin says.

Changes to FDA regulations implemented as part of the CARES Act this spring have left dermatologists and their patients scrambling to access hydroquinone. Hydroquinone can no longer be sold over the counter, but it can be ordered by prescription from an FDA-Registered 503B Outsourcing Facility.

Prescription drugs containing hydroquinone that do not go through the NDA or aNDA process are considered misbranded. TriLuma (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%, Galderma)—the only prescription hydroquinone-containing formulation to have come to market under an NDA—remains available on the market.

“Not only patients, but many of my physician colleagues are not aware,” cautions Alia Sampson Brown, MD, Co-managing Partner at Georgia Dermatology Partners. “The CARES Act was such a huge piece of legislation, but this fell through the cracks of public awareness…I am definitely spreading the word to my colleagues and patients about it.”

Provisions of the CARES Act also have implications for sunscreen formulations. “Under the CARES Act, essentially FDA will be moving from rule-making process to an administrative order process, which means that it would not be taking as long to implement a monograph,” says Henry Lim, MD, who spoke about the change during the San Diego Dermatology Symposium virtual program this fall. “And also, as importantly, in the CARES Act, that means that there will not be a final rule. The FDA is required to issue a proposed administrative order by September 27 of next year, 2021. And once the final administrative order has been issued, then industry would have at least one year to comply with what they offer on the shelves in the United States.”

EQUITY AND DIVERSITY IN FOCUS

As national attention has turned to systemic racism and issues of racial injustice, the medical community is addressing disparities in healthcare. At a Special Meeting of the American Medical Association’s (AMA) House of Delegates (HOD) meeting last month, physicians adopted a new policy that recognizes racism as a public health threat and commits to actively work on dismantling racist policies and practices across all of health care.

The Skin of Color Society, NEJM Group, and VisualDx have launched a four-part webinar series, “The Impact of Skin Color and Ethnicity on Clinical Diagnosis and Research.” Organizers say the series—free to attend and geared to health care workers—will delve into longstanding problems in education, research, and patient care as well as introduce ways to improve outcomes in marginalized patients.

Studies have shown patients with darker skin experience worse health outcomes than patients with lighter skin. The free series will address the socioeconomic factors, structural racism, and implicit bias that lead to disparities, as well as look at how the medical community can address these issues by offering tangible, real-world solutions, a statement announcing the initiative states.

“I hope doctors will diagnose better and have better therapeutic regimens as a result of this webinar series,” observes Art Papier, MD, Founder and CEO of VisualDx. “I also hope they will make a commitment to continue learning more about diagnosing and treating patients of color in a culturally sensitive manner. Providing high quality, highly reliable care is essential to physicians’ duty to do no harm, and that applies to all patients we treat.

“Racial bias remains evident across the entire care pathway, from access to care to the quality of care delivered. We’ve seen COVID-19 devastate communities of color in particular, shining light once again on glaring inequities in medicine and what’s truly at stake here.”

Columbia University School of Nursing has announced the establishment of the Center for Research on People of Color (CRPC). With the growing demand for health equity and justice in our society, the Center will provide multidisciplinary resources for research and educational programming designed to address injustices in health care that disproportionately affect communities of color. The center’s body of research will focus on conditions and diseases that disproportionately affect minority populations, such as hypertension, obesity, diabetes, maternal/child health and poor birth outcomes, LGBTQ health, and genomics of health and disease.

THERAPEUTIC DEVELOPMENTS IN MEDICAL DERMATOLOGY

Under Review

Abrocitinib, Pfizer. FDA has granted Priority Review designation to the NDA for abrocitinib (100mg and 200mg), an investigational oral once-daily Janus kinase 1 (JAK1) inhibitor, for the treatment of moderate to severe atopic dermatitis (AD) in patients 12 and older. The FDA is expected to make a decision in April 2021.

The European Medicines Agency (EMA) has also accepted the Marketing Authorization Application (MAA) for abrocitinib in the same patient population with a decision anticipated in the second half of 2021.

Filings were based on the results of a robust Phase 3 clinical trial program, across which abrocitinib demonstrated statistically superior improvements in skin clearance, disease extent, and severity, as well as rapid improvements (measured as early as Week 2) in itch versus placebo. Abrocitinib also demonstrated a consistent safety profile across trials and was generally well-tolerated.

Abrocitinib received Breakthrough Therapy designation from the FDA for the treatment of patients with moderate to severe AD in February 2018.

Bimekizumab, UCB. The FDA and the EMA have accepted the Biologics License Application (BLA) and Marketing Authorization Application (MAA), respectively, for bimekizumab for the treatment of adults with moderate to severe plaque psoriasis.

The marketing application submissions for bimekizumab are based on data from global Phase 3 studies in which the drug met all primary endpoints; bimekizumab-treated patients achieved superior skin clearance at week 16 compared to those who received placebo and Humira (adalimumab) as measured by the Psoriasis Area and Severity Index (PASI 90) and an Investigator Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1).

Approvals and Label Updates

Dupixent, Sanofi/Regeneron. Dupilumab received FDA approval for children aged six to 11 years with moderate to severe atopic dermatitis (AD).

Dupixent comes in two doses, prescribed based on weight (300mg every four weeks for children ≥15 to <30kg and 200mg every two weeks for children ≥30 to <60kg, following an initial loading dose) as a pre-filled syringe.

Approval is based on data from a pivotal Phase 3 trial in which more than twice as many children achieved clear or almost clear skin and more than four times as many achieved itch reduction with Dupixent plus topical corticosteroids (TCS) compared to TCS alone. Children treated with Dupixent and topical corticosteroids (TCS) experienced approximately 80 percent average overall disease improvement.

“The approval of Dupilumab down to age 6 has really been revolutionary. Every day in my practice I see the incredible impact of atopic dermatitis on children and their families,” observes Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children’s Hospital-San Diego. “It is actually amazing how many children are walking around with high body surface areas of eczema, profound sleep disturbance and many of the medical and life issues associated with AD. Many families are frustrated, or resigned, or have accommodated to the disease. The approval has rapidly evolved the therapeutic landscape, markedly increased the ability to access the drug in the extended age group, and puts us in the position of really changing the lives of these children and their families.”

The safety profile of Dupixent with TCS was similar to what was observed in adults and adolescents with atopic dermatitis, and consistent through 52 weeks.

Photo Op

Now is the time to rethink your marketing materials.

Before and after images as well as other marketing stills and social media content have always been among the best ways to market your practice and help future patients get to know more about you and your style, but COVID-19 has forced many dermatologists to make changes to their marketing materials and other aspects of their practice.

“We require mask use when in the office, and now some of our marketing and social media imagery reflect these new guidelines. We have strict protocols in place to offer our patients a safe environment,” says Sapna Palep, MD, Founder of Spring Street Dermatology with three offices in New York City.

Dr. Palep recently took a group shot of her team of dermatologists at Spring Street Dermatology with masks on for an email marketing campaign. “All of our video shoots and press interviews with various media outlets include masks,” she says. “We were in the process of updating our web site imagery and felt it was important to take some images that reflect our new normal and convey to patients that we strictly adhere to these standards.”

That’s not all that has changed at her practices due to the COVID-19 pandemic.

“Along with consistent mask use, we now have extra protocols in place to limit the amount of people in the office to adhere to social distancing guidelines,” she explains. “We also have a questionnaire for every patient and are taking temperatures [and] are cleaning and sterilizing each room in between patients and have stepped up our efforts to keep the office clean.”

FDA also approved a 300mg single-dose pre-filled pen for Dupixent. 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, asthma, and chronic rhinosinusitis with nasal polyposis (CRSwNP), for at-home administration.

Enstilar, LEO Pharma. The US Prescribing Information (USPI) for Enstilar (calcipotriene and betamethasone dipropionate) Foam from LEO Pharma A/S now includes data on long-term use in adults with plaque psoriasis, following FDA approval of a supplemental New Drug Application (sNDA).

The sNDA submission was based on data from the Phase 3 PSO-LONG clinical trial in which participants (n=545) were randomized to receive Enstilar Foam or vehicle foam twice-weekly on two non-consecutive days for up to 52 additional weeks. Subjects experiencing a loss of response (defined as a PGA score of at least “mild”) were treated once-daily with Enstilar Foam for four weeks, and those who regained a PGA score of “clear” or “almost clear” after four weeks then resumed randomized long-term use treatment.

Those treated long-term twice-weekly with Enstilar Foam had a longer time to first loss of response and fewer losses of response than those using vehicle foam. No clinically relevant effects on calcium metabolism or the HPA axis were observed. The rate of adverse events (AEs) was comparable across treatment groups.

Eucrisa, Pfizer. Crisaborole ointment became the first and only steroid-free, topical prescription medication for mild to moderate AD in patients as young as three months of age, with an FDA label expansion for Eucrisa ointment 2%. Eucrisa was previously approved for use in adults and children 2 years of age and older.

Approval for the expanded indication was supported by data from a Phase 4, open-label, clinical study in which crisaborole ointment 2%, was well-tolerated and demonstrated effectiveness in patients with mild to moderate AD with no new safety signals identified.

Jublia, Ortho Dermatologics. Efinaconazole topical solution 10%, is now approved for children as young as six years of age. Jublia was first approved in June 2014 in patients 18 years and older.

The safety, pharmacokinetics and efficacy of Jublia in patients ages six to 16 years old were evaluated in a multicenter, open-label, single-arm Phase 4 study that enrolled 62 patients with mild to severe onychomycosis.

Keytruda, Merck. FDA 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. 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).

Nevisense 3.0, SciBase. The third generation of the Nevisense system for early melanoma detection is an AI-based point-of-care system that used electrical impedence spectrsoscopy (EIS) for the non-invasive evaluation of irregular moles. It is the only FDA-approved system available for melanoma detection in the US and the only device based on EIS.

The AMA recently approved a new CPT procedure code for the use of EIS for detection of melanoma, and it is expected to be in use by mid-2021.

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

Seysara is a novel tetracycline-derived oral antibiotic developed specifically for the treatment of acne, and was approved by the FDA in October 2018. Since its launch in January 2019, Seysara has been prescribed for close to 100,000 patients.

Stelara, Janssen Pharmaceutical Companies of Johnson & Johnson. Ustekinumab is now approved for pediatric patients (6-11 years of age) with moderate to severe plaque psoriasis. Approval of Stelara for pediatric use is based on results from the CADMUS Junior study. In the open-label, single-arm, multicenter Phase 3 clinical trial of 44 patients with moderate to severe plaque psoriasis, 77 percent of patients achieved clear or almost clear skin at week 12 after two doses.

Taltz, Eli Lilly and Company. FDA approved the supplemental Biologics License Application (sBLA) ixekizumab injection, 80 mg/mL for the treatment of pediatric patients ages 6 to under 18 with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

In Phase 3 trials, 89 percent of pediatric patients treated with Taltz achieved PASI 75, compared to 25 percent of patients treated with placebo.

Tremfya, Janssen Pharmaceutical Companies of Johnson & Johnson. Guselkumab is the first interleukin (IL)-23 approved for active PsA in adult patients.

Results of the Phase 3 clinical trials. DISCOVER-1 and DISCOVER-2, published in The Lancet, shows that a significant percentage of patients treated with Tremfya reached the studies’ primary endpoint of ACR20 at 24 weeks, with 52 and 64 percent of patients achieving an ACR20 response compared to 22 and 33 percent in patients treated with placebo in DISCOVER-1 and DISCOVER-2, respectively.

Winlevi, Cassiopea. The FDA approved clascoterone cream 1% for the treatment of acne in patients 12 years and older.

Laboratory studies suggest that clascoterone competes with androgens, specifically dihydrotestosterone (DHT), for binding to the androgen receptors within the sebaceous gland and hair follicles. In pivotal clinical trials, Winlevi demonstrated treatment success and reductions in acne lesions and was well tolerated when used twice a day. The most frequently observed local skin reaction was mild erythema.

Wynzora Cream, MC2 Therapeutics. Calcipotriene and betamethasone dipropionate, w/w 0.005%/0.064% cream is approved for once-daily topical treatment of plaque psoriasis in adults 18 years of age or older.

Approval is based on results of the US Phase 3 clinical trial against active comparator Taclonex Topical Suspension (calcipotriene and betamethasone dipropionate, w/w 0.005%/0.064%). At week eight, there was a 14.6 percent difference in the primary efficacy endpoint—the proportion of patients with PGA treatment success, defined as at least a 2-grade improvement from baseline in PGA to “clear” or “almost clear”—for Wynzora Cream, versus active comparator.

MC2 Therapeutics has entered a Collaboration Agreement with EPI Health, LLC on the commercialization of Wynzora Cream (calcipotriene and betamethasone dipropionate, w/w 0.005%/0.064%) in the US. MC2 Therapeutics retains full ownership of Wynzora Cream under the Collaboration Agreement.

Zilxi, Vyne Therapeutics. FDA approved minocycline topical foam, 1.5% for the treatment of inflammatory lesions of rosacea in adults. Zilxi is the first minocycline product of any kind to be approved by the FDA for use in rosacea.

Zilxi is formulated with proprietary Molecule Stabilizing Technology (MST) platform to effectively deliver minocycline in a foam-based vehicle.

Linda Stein Gold, MD, director of dermatology clinical research at Henry Ford Health System in Detroit says, “Unlike an oral medicine that is absorbed through the stomach into the bloodstream, ZILXI has demonstrated a low systemic absorption. The foam vehicle was formulated with naturally moisturizing oils.”

She says the data show Zilxi is well-tolerated. “In rosacea patients I worry equally about tolerability as safety. Zilxi is proven safe and well tolerated on already-sensitive skin. Patients saw a 60-61 percent reduction in the number of inflammatory lesions by Week 12 vs. 49-54 percent with vehicle. Some patients even saw results as early as Week 4. Also, 49-52 percent of patients using Zilxi achieved ‘clear’ or ‘almost clear’ skin by Week 12 vs. 39-43 percent with vehicle.”

Launches

Arazlo, Ortho Dermatologics. Tazarotene Lotion, 0.045% hit the market after receiving FDA approval 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. Read more about Arazlo in the “Clinical Focus” column in this edition on page 44.

Sklice, Arbor Pharmaceuticals. Sklice (ivermectin) lotion, 0.5% is now approved for OTC sale. Sklice was originally FDA approved as a prescription treatment for head lice infestation in patients six months of age and older in February 2012. Sklice will be marketed in the United States as a nonprescription drug and will no longer be available as a prescription drug.

CLIMATE WATCH

The vast majority of dermatologists (95.6 percent) believe climate change is occurring, and 88.6 percent indicated that climate change will impact the incidence of skin diseases in their areas, according to an online survey conducted by the International Society of Dermatology’s (ISD) Climate Change Committee and published in the International Journal of Dermatology (IJD).

Louise K. Andersen, MD, chair of the ISD’s Climate Change Committee and lead researcher of the survey, tells DermWire TV. “What surprised me the most was a relatively high number of respondents indicated that climate change is already affecting their dermatological practice. Many had already noted change in the pattern of skin diseases in their paients.”

Of note, 88 percent of dermatologists thought that dermatologists should play an advocacy role in climate change-related health issues.

NEW COVERAGE DECISIONS

Cigna has issued a new medical coverage policy for excimer laser therapy for vitiligo, according to Strata Skin Sciences, maker of the XTRAC excimer laser. Cigna previously deemed such treatment cosmetic and not medically necessary.

Vyne Therapeutics’ Zilxi (minocycline) is covered on Express Scripts’ National Preferred, Flex, and Basic commercial formularies effective October 2, 2020.

The Medicare Administrative Contractor Palmetto GBA MolDx issued a final local coverage determination for DermTech, Inc.’s Pigmented Lesion Assay (PLA) used to help rule out primary cutaneous melanoma and guide biopsy decisions of melanocytic skin lesions with one or more clinical or historical characteristics suggestive of melanoma. Clinicians with sufficient skill and experience to decide whether a pigmented lesion should be biopsied may order the PLA test, with up to two tests allowed per patient for each date of service.

This review is intended to be comprehensive but may not be all-inclusive.

For a review of developments in cosmetic dermatology, visit the website of our sister publication: ModernAesthetics.com.