Recent Developments

Otezla Becomes First Oral Psoriasis Treatment Approved Across All Disease Severities

Amgen’s apremilast (Otezla) is now approved for the treatment of adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy. This expanded indication makes Otezla the first oral treatment approved in adult patients with plaque psoriasis across all severities, including mild, moderate, and severe.

FDA approval is based on findings from the Phase 3 ADVANCE trial, in which five times as many adults with mild to moderate plaque psoriasis receiving oral Otezla 30mg twice daily achieved the primary endpoint of Static Physician’s Global Assessment (sPGA) response at week 16 compared to placebo (21.6 versus 4.1 percent). Otezla also demonstrated statistically significant improvements in key symptoms, such as Whole Body Itch NRS response (43.2 versus 18.6 percent), and a difficult-to-treat area, the scalp, measured by Scalp Physician’s Global Assessment (ScPGA) response (44 versus 16.6 percent), at week 16 compared to placebo.

Adverse events observed in the trial were consistent with the known safety profile of Otezla. The most commonly reported (≥five percent) treatment-emergent adverse events with Otezla treatment were diarrhea, headache, nausea and nasopharyngitis.

LEO Pharma’s Adbry Approved for Moderate to Severe AD

FDA has approved Adbry (tralokinumab-ldrm) from LEO Pharma Inc., for the treatment of moderate to severe atopic dermatitis in adults 18 years or older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Adbry is the first FDA-approved biologic that specifically binds to and inhibits the IL-13 cytokine, a key driver of atopic dermatitis signs and symptoms.

The approval of Adbry is based on safety and efficacy results from the ECZTRA 1, 2, and 3 pivotal Phase 3 trials, which included nearly 2,000 adult patients with moderate to severe atopic dermatitis.

In all three pivotal trials, Adbry 300mg every other week alone or with topical corticosteroids (TCS) as needed met the primary endpoints at Week 16 as measured by an Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and/or at least a 75 percent improvement in the Eczema Area and Severity Index score (EASI-75), and the secondary endpoint of reduction of weekly average Worst Daily Pruritus NRS of ≥ 4 points on the 11-point itch NRS. Adbry can be used with or without topical corticosteroids.

In clinical trials, the safety of Adbry was well established with an overall frequency of adverse events comparable with placebo.

Adbry will be available in a 150mg/mL prefilled syringe for subcutaneous injection with an initial dose of 600mg followed by 300mg every other week. A dosage of 300mg every four weeks may be considered for patients below 100kg who achieve clear or almost clear skin after 16 weeks of treatment.

FDA Accepts NDA for Boehringer Ingelheim’s Spesolimab for GPP

FDA has accepted a Biologics License Application (BLA) and granted Priority Review for Boehringer Ingelheim’s spesolimab for the treatment of generalized pustular psoriasis (GPP) flares.

The FDA has granted spesolimab Orphan Drug Designation for the treatment of GPP, and Breakthrough Therapy Designation for spesolimab for the treatment of GPP flares in adults.

Spesolimab is a novel, humanized, selective antibody that blocks the activation of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogeneses of several autoimmune diseases, including GPP. Spesolimab is also under investigation for the prevention of GPP flares and for the treatment of other neutrophilic skin diseases, such as palmoplantar pustulosis (PPP) and hidradenitis suppurativa (HS).

Lilly’s Lebrikizumab Plus Topical Corticosteroids Offer Improvement and Itch Relief in Atopic Dermatitis

Lebrikizumab significantly improved disease severity when combined with topical corticosteroids (TCS) in moderate to severe atopic dermatitis (AD) in Eli Lilly and Company’s third pivotal Phase 3 trial (ADhere). By Week 16, the study met all primary and key secondary endpoints for patients on the lebrikizumab combination arm.

Lebrikizumab is a novel, investigational monoclonal antibody (mAb) that binds soluble IL-13 with high affinity, has high bioavailability, a long half-life and blocks IL-13 signaling. In people with AD, the IL-13 protein—a central pathogenic mediator in the disease—is overexpressed, driving multiple aspects of AD pathophysiology by promoting T-helper type 2 (Th2) cell inflammation and resulting in skin barrier dysfunction, itch, infection, flares and hard, thickened areas of skin.

The primary endpoints were Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin with a reduction of at least two points from baseline and at least a 75 percent change from baseline in the Eczema Area and Severity Index (EASI) score, both at Week 16.

Lebrikizumab in combination with TCS also achieved all key secondary endpoints versus placebo in combination with TCS in patients with AD, including skin improvement, itch relief, improvement in interference of itch on sleep, and quality of life. Key secondary endpoints were measured by EASI, the Pruritus Numeric Rating Scale, Sleep-Loss due to Pruritus, and the Dermatology Life Quality Index.

Safety results in the 16-week placebo-controlled ADhere study were consistent with the 16-week period of two monotherapy studies in the lebrikizumab Phase 3 AD program.

In August 2021, Lilly announced top-line data from ADvocate 1 and ADvocate 2 showing lebrikizumab as a monotherapy met primary and all key secondary endpoints including itch, and interference of itch on sleep and quality of life at Week 16.

Lilly has exclusive rights for development and commercialization of lebrikizumab in the US and the rest of world outside Europe. Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including AD, in Europe.

Dermatologist’s Book Explores Doctor-Patient Connections

When Christine J. Ko, MD, a Professor of Dermatology and Pathology at Yale University, “failed spectacularly” with a patient—someone she knew personally—she started to rethink her approach to clinical interactions to find ways to do better.

Her personal experiences, along with a good deal of research, resulted in How to Improve Doctor-Patient Connection, which was published by Routledge this fall.
The book, which is available through various outlets, including Amazon.com, offers actionable steps for improving communication between health professionals and patients based on visual, auditory, and emotional understanding from the principles of cognitive psychology.

“This how-to text includes several practical applications that can be applied to health care encounters, enabling readers to form habits based on visual analysis of body language, auditory information from language and tone of voice, and logical emotion perception that will allow for improved doctor-patient connection,” the description reads.

As practices continue to adapt and regrow in light of the challenges of the COVID-19 pandemic, Dr. Ko says the book may be particularly relevant to those assessing the doctor/patient connection.

FDA Accepts sNDA for Opzelura for Vitiligo

FDA has accepted for Priority Review the supplemental New Drug Application (sNDA) for ruxolitinib cream 1.5% (Opzelura, Incyte) a topical JAK inhibitor from Incyte, as a potential treatment for adolescents and adults with vitiligo.

The sNDA is supported by data from the Phase 3 TRuE-V clinical trial program evaluating the safety and efficacy of ruxolitinib cream in more than 600 people with non-segmental vitiligo, age 12 and older. Results from the Phase 3 program were presented at the 30th European Academy of Dermatology and Venereology congress. The data showed that at Week 24, 29.9 percent of patients applying ruxolitinib cream achieved ≥75 percent improvement from baseline in the facial Vitiligo Area Scoring Index (F-VASI75), the primary endpoint.

The PDUFA target action date is April 18, 2022.

Rinvoq Gets FDA Nod for Psoriatic Arthritis

The FDA has approved Rinvoq (upadacitinib; 15mg, once daily) for the treatment of adults with active psoriatic arthritis (PsA) who have had an inadequate response or intolerance to one or more tumor necrosis factor blockers.

The FDA approval is supported by data from two pivotal Phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, which assessed the efficacy, safety and tolerability of Rinvoq (AbbVie) in patients with PsA. Across the Phase 3 clinical trials, Rinvoq met its primary endpoint of ACR20 at week 12 with patients taking Rinvoq 15mg achieving significantly higher ACR20 responses versus placebo.

Top Researcher of Itch and Inflammation to Join Mount Sinai’s Department of Dermatology

Brian S. Kim, MD, MTR, FAAD, will join Mount Sinai Health System as Director of the newly established Mark Lebwohl Center for Neuroinflammation and Sensation. Dr. Kim will also be Vice Chair of Research of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai, and Site Chair of Dermatology at Mount Sinai West and Mount Sinai Morningside.

Dr. Kim will work collaboratively with Emma Guttman-Yassky, MD, PhD, Waldman Professor and System Chair of Dermatology; Miriam Merad, MD, PhD, Director of the Precision Immunology Institute; and Eric J. Nestler, MD, PhD, Director of The Friedman Brain Institute. Dr. Kim will hold joint appointments in Dermatology and the two institutes.

Dr. Kim’s research is rooted in understanding the regulatory mechanisms that control neuroimmune interactions at the skin barrier surface and examining how immune responses interface with the sensory nervous system to regulate inflammation, sensation, and immunity.

The Mark Lebwohl Center for Neuroinflammation and Sensation will advance multidisciplinary research, bringing together skin biology, immunology, and neuroscience. By leveraging its influential scientific advances, coupled with outstanding clinical expertise, the state-of-the-art Research Center will provide world-class clinical care for patients with chronic itch and other sensory disorders. The ultimate goal is to bring therapeutic innovations through fundamental new science and cutting-edge clinical trials towards highly unmet sensory and neuroinflammatory disorders.

CLOSE UP with Mark Lebwohl, MD, FAAD

A non-steroidal topical that’s as effective as steroids but isn’t a steroid has been considered a holy grail of sorts in dermatology—especially for psoriasis patients with plaques in thin-skinned areas.

And now, Phase 3 trials suggest that Dermavant’s novel, steroid-free topical Tapinarof may fit this bill, says Mark Lebwohl, MD, FAAD, Dean of Clinical Therapeutics and Waldman Professor and Chairman of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York.

Here, Dr. Lebwohl discusses the study results which are published in the New England Journal of Medicine.

Why is this topic important to study?

Mark Lebwohl, MD, FAAD: There is a big need for non-steroidal topicals in dermatology specifically in psoriasis. Many of our patients have involvement of their groin, face, or axilla, and those are thin-skinned areas where patients get in trouble when they use steroids. We really need non-irritating creams and ointments.

Describe the research and your findings.

Dr. Lebwohl: PSOARING 1 and PSOARING 2 were identical double-blind, placebo-controlled pivotal trials that enrolled 1,025 patients aged 18-75 who had a Physician’s Global Assessment (PGA) baseline score of 2 (mild), 3 (moderate), or 4 (severe), and plaque psoriasis covering up to 20 percent of their body surface area. Following a screening period, eligible patients were randomly assigned in a 2:1 ratio to Tapinarof cream 1% or vehicle cream once daily. Participants were stratified at entry by baseline PGA score. Trial visits occurred at screening, baseline, and weeks 2, 4, 8, and 12 during the treatment period. Topical Tapinarof cream was highly effective, and that efficacy is durable in those who continue on the medication. For those who clear completely, psoriasis remains in remission for approximately four months after discontinuation of the treatment. And the treatment was safe, even on sensitive skin sites. The most common side effect was mild to moderate folliculitis, and few patients discontinued for that.

What is the next step?

Dr. Lebwohl: The pivotal trials are completed, so the next step is for the company to apply for approval from the FDA.

Data Show Long-term Benefit, Tolerability of Guselkumab

Historically, a proportion of patients treated for psoriasis (PsO) and psoriatic arthritis (PsA), axial spondyloarthritis, and rheumatoid arthritis discontinue therapies after two to three years, often citing lack of benefit over time, observes Phillip Mease, MD, Director of Rheumatology Research at the Swedish Medical Center/Providence St. Joseph Health and Clinical Professor at the University of Washington School of Medicine.

That’s important context for considering data Dr. Mease presented from six new analyses of Phase 3 data from the DISCOVER-1 and DISCOVER-2 clinical trials, which demonstrate Tremfya (guselkumab) inhibited radiographic progression versus placebo and provided substantial and durable improvements in joint signs and symptoms, axial symptoms, enthesitis, dactylitis, and pain among adult patients with active PsA over time. The majority of Tremfya-treated patients who achieved an ACR20, ACR50, or ACR70 response at week 52 maintained the response at week 100, with response rates for ACR50 and ACR70 increasing through the second year of treatment.

The data, presented at the American College of Rheumatology (ACR) Convergence last fall, also showed a safety profile consistent between adults with active PsA through two years and adults with moderate to severe PsO through five years.

“All of our current drugs tend to lose efficacy over time, so having data that shows sustained benefit over time is important,” says Dr. Mease. “The longer that you can go with a drug and still show efficacy is such an important item because of this phenomenon. So we’re always looking for that. Patients really like it when their IL-23 maintains its effectiveness, because then they don’t have to think about switching to a drug that might have a thornier safety profile.”

Data demonstrate that the response curve with guselkumab continues to improve beyond 16 weeks. “When I talk to patients at the 16-week mark or the 24-week mark, I can honestly say to them, ‘There might still be some further improvement. So even if you’re not quite as satisfied as you might be, there’s still room for being in a better state,’” Dr. Mease says. Compared to daily oral medication, patients taking Tremfya inject themselves just once every two months.

“The fact that we can now demonstrate two years’ worth of not having radiographic progression, further structural damage is really reassuring,” Dr. Mease says.

Comprehensive efficacy and safety data from the DISCOVER–2 trial of guselkumab also were published in Arthritis & Rheumatology in November. The final results of the first two-year clinical trial investigating a selective interleukin (IL)-23 inhibitor therapy in PsA show that a majority of Tremfya-treated biologic-naïve adult patients with active PsA achieved improvements in joint signs and symptoms (ACR 20/50/70) and complete skin clearance (IGA 0) that were maintained or increased over time.

Five-year data from the VOYAGE studies of guselkumab, published last month in the Journal of the American Academy of Dermatology, demonstrate a favorable safety profile in adult patients with moderate to severe PsO with a high retention rate of nearly 80 percent for Tremfya-treated patients across both VOYAGE studies. VOYAGE 1 assessed patients who started treatment on adalimumab and switched to guselkumab, while VOYAGE 2 assessed withdrawal and retreatment. Low rates of adverse events were reported.

The reported data reflects a total of 7,166 patient-years (PY). Overall, 1,349 of 1,721 guselkumab-treated patients (78.4 percent) continued treatment through week 252. Event rates at week 264 were generally similar to those at week 52 in VOYAGE 1 and at week 100 in VOYAGE 2. Rates of adverse events of interest were low. These include serious infections (0.85/100 PY), nonmelanoma skin cancer (0.34/100 PY), malignancies other than nonmelanoma skin cancer (0.45/100 PY), and major adverse cardiovascular events (0.29/100 PY). The authors note that year-to-year variability was evident, but no increasing trend was observed

Dupilumab: Data Show Safety, EfficaCy in Patients as Young as Six Months

Data demonstrating the safety and efficacy of Sanofi and Regeneron’s Dupixent® (dupilumab) in pediatric patients as young as six months were presented for the first time at the recent Revolutionizing Atopic Dermatitis (RAD) Virtual Conference.

Amy S. Paller, MD presented results of a trial showing that dupilumab significantly improved signs and symptoms of moderate to severe AD in children aged six months to five years with a favorable safety profile. In an open-label extension trial of dupilumab in children aged six to 11 years, treatment resulted in substantial and sustained long-term reduction in AD signs and symptoms, as well a favorable safety profile. This marks the first presentation of data for use of dupilumab in children as young as six months and the first presentation of longer-term (one year) data in children six to 11 years.

Several poster presentations addressed the influence of dupilumab treatment on various aspects of atopic dermatitis. Joseph Merola, MD and colleagues showed that dupilumab significantly improved overall sleep vs placebo in adults with moderate to severe AD. The team used a novel scale to measure sleep quality.

Stephan Weidinger, MD, PhD and colleagues reported on AD severity and outcomes in infants/preschoolers (aged six months to six years) in 18 countries from five regions, including North America, Latin America, Europe, Middle East/Eurasia, and East Asia, from the EPI-CARE study.

One or more atopic comorbidity was reported in 88.3 percent, 92.1 percent, and 95.8 percent of patients with mild, moderate, and severe AD, respectively. Infants/preschoolers with moderate or severe AD had worse itch, skin pain, and sleep disturbances over the past 24 hours, compared with those with mild AD across regions. The majority (78.3 percent) of preschoolers aged four to <six years missed at least one school day in the past four weeks, with a mean (SD) of 5.1 (5.7) days lost in mild AD, 7.3 (7.1) days in moderate AD, and 12.1 (7.8) days in those with severe AD.

Robert Bissonnette, MD led a team that assessed the effects of dupilumab treatment on rates of transepidermal water loss (TEWL) in individuals with AD. At Week 16, there were no statistically significant differences in the adjusted mean TEWL distribution between lesional and non-lesional skin in AD patients and matched healthy volunteers.

Pulse NPS Technology Could Be Used for Syringomas

Pulse Bioscience’s nano-pulse stimulation or NPS technology shows potential for the treatment of syringoma. The CellFX NPS system uses electrical energy to non-thermally clear cells while sparing adjacent non-cellular tissue.

In a feasibility study conducted on five subjects with a total of 24 syringoma lesions outside the orbital rim, positive results demonstrated 83 percent efficacy, no residual skin effects, and high patient satisfaction.

Oculoplastic surgeon and trial investigator Brian Biesman, MD reported the study results at the virtual annual meeting of the American Society of Dermatologic Surgery last fall.

Patients Eye Medical Cannabis for Skin Disorders

Patients with dermatologic conditions are open to trying medical cannabis products (MCPs) as potential treatments, according to a new study from George Washington University (GW) School of Medicine and Health Sciences (SMHS) and University of Maryland researchers. MCPs are cannabis or cannabis-derived products that contain tetrahydrocannabinol or THC and/or cannabidiol, known as CBD.

The research team surveyed more than 500 adult patients on their beliefs and habits related to MCPs. Results showed 17.6 percent of patients used an OTC cannabis product to treat skin conditions such as acne and psoriasis, without a recommendation from a dermatologist. Of the two-thirds of respondents who had seen a dermatologist previously, about 20 percent had been recommended an OTC product, primarily for acne and psoriasis. Most used OTC products, with only eight percent reporting use of an MCP that required a Department of Health-approved card. Importantly, 88.8 percent of all respondents supported the use of medical cannabis for dermatologic disease. The majority of respondents also reported that they would be willing to try an MCP if recommended by a dermatologist.