From new vaccines to the advent of new neurotoxins

It's an extraordinary time in dermatology, says Mark Lebwohl, M.D., chair of dermatology at Icahn School of Medicine in Mount Sinai.

Today, there are treatments for conditions that didn’t have viable treatment options 10 or 20 years ago, says Dr. Lebwohl, who directed the "What's New in Dermatology," session on Feb. 20 during American Academy of Dermatology annual meeting in San Diego.

"Who would have thought about talking about PASI [Psoriasis Area Severity Index] 100? That term hardly existed 10 years ago. Now, every drug that comes out is expected to reach not only PASI 75 but also PASI 100," Dr. Lebwohl says.

VACCINES IN DERMATOLOGY

"Gardasil 9 (Merck), which is the new human papillomavirus (HPV) vaccine, is particularly important, not only because it covers more of the viruses that are emerging as culprits in genital warts, but the long-term hope is that it will reduce cancers," he said. 

Shingrix (GSK), which is the new recombinant, adjuvanted FDA approved shingles vaccine, has several advantages over Zostavax (zoster live vaccine, Merck).

"It's not a live virus, so many of our patients who are getting biologic therapies or immunosuppressant therapies can more safely be given this vaccine than the preceding one. Secondly, it is substantially more effective," Dr. Lebwohl said.

PSORIASIS TREATMENTS

Janus kinase (JAK) inhibitors continue to progress as viable treatments in psoriasis and other conditions.

"These have been tested in both oral and topical forms and have been effective for alopecia areata, vitiligo and for atopic dermatitis. So, we do have this new class of drugs that is very promising for some conditions that we've had great difficulty treating," he says. 

And, new psoriasis biologics - some of which are approved and block interleukin (IL)-17 and IL-23 - are the most effective treatments dermatologists have seen for plaque psoriasis, he said.

"They're very rapidly effective and highly effective, with significant numbers of patients (we're talking about numbers above 80 percent) achieving not only PASI 75, but even PASI 90 and PASI 100," Dr. Lebwohl said.

SURGICAL DERMATOLOGY

Targeted treatments for advanced and metastatic non-melanoma skin cancers have been impactful, said Desiree Ratner, M.D., director of the Comprehensive Skin Cancer Center at Mount Sinai Downtown.

“What's new in surgical dermatology these days relates to the management of advanced non-melanoma skin cancers, for which we really haven't had any options until quite recently,” Dr. Ratner says. “We now have two targeted therapies for advanced basal cell carcinomas, vismodegib (Erivedge, Genentech), which was FDA approved in 2012, and sonidegib (Odomzo, Sun Pharma), FDA approved in 2015--both oral medications with local disease control rates of approximately 80 percent, and both of which can cause dramatic shrinkage in large tumors.”

The next exciting development relates to managing patients with very high-risk squamous cell carcinomas.

“Agents now being used to treat aggressive squamous cell carcinomas include cetuximab (Erbitux, Eli Lilly and Company), which is an epidermal growth factor receptor inhibitor, and pembrolizumab (Keytruda, Merck), a programmed cell death protein 1 (PD-1) inhibitor,” Dr. Ratner says. “While neither of these are yet FDA-approved specifically for squamous cell carcinoma, there have been promising results published in the literature, and it appears as though we are on the verge of being able to effectively manage this very aggressive and at times lethal tumor.”

Yet another big development, according to Dr. Ratner, concerns patients with Merkel cell carcinoma.

“It turns out that Merkel cell carcinomas respond so well to a new programmed cell death ligand 1 (PD-L1) inhibitor called avelumab (Bavencio, EMD Serono and Pfizer) that it was FDA approved in 2017 for patients with metastatic Merkel cell carcinoma,” she said.

COSMETIC DERMATOLOGY

Important trends could impact demand for cosmetic dermatology, according to Kimberly J. Butterwick, M.D., a dermatologist who practices in San Diego.

More men are likely going to be seeking cosmetic dermatology since cosmetic procedures have become more accepted among men. And, demand among women for feminine and vaginal rejuvenation will continue to grow.

This year might also offer new options in and new indications for neurotoxins.

There’s a new neurotoxin is called daxibotulinumtoxinA (RT002, Revance Therapeutics), for which phase 2 studies were published November 2017. That research showed that with a 40-unit dose, the mean duration was 24 weeks, according to Dr. Butterwick.

Allergan just got the third indication for the use of onabotulinumtoxinA (Botox Cosmetic) in the forehead, according to the dermatologist.

“We would look forward to a company getting a masseter or platysma band indication, but I know of no plans at present,” Dr. Butterwick says. “Even though we use the neurotoxins for these indications off label, if they go through FDA approval for a given area, then [manufacturers] can advertise and make patients more aware that these treatments are available.”

The same is true for fillers - more competition and new indications.

Fillers on the horizon include products that aren’t made by the major pharma companies. Two brands recently were approved by the FDA: Revanesse Versa (Revanesse USA) and Teosyal (Teoxane).

Dr. Butterwick says a big newsmaker in cosmetic dermatology in the coming years could be FDA approval of a hair removal laser capable of treating red, blonde and gray. The device delivers silver nanoparticles into hair follicles, which act as targets for laser absorption.

“The hair removal device has passed its proof-of-concept studies but still is a few years off from being in our hands. One other exciting investigational device is a needling device that specifically extracts little, tiny thin columns of skin, causing the skin to heal and shrink, without scarring. Lastly, something that is relatively new this year and will increase is the use of absorbable sutures to lift the skin. I think that we are getting closer to our quest of being able to do a facelift without surgical scars,” Dr. Butterwick says.

PEDIATRIC DERMATOLOGY

There’s an explosion of interest and activity in atopic dermatitis, according to panel member Lawrence F. Eichenfield, M.D., of the University of California, San Diego.

Leading the revolution: crisaborole ointment (Eucrisa, Pfizer), the first new drug in class since 2001. Studies are showing long-term safety, with more than a year of use.

“The first biologic agent for atopic dermatitis, dupilumab (Dupixent, Sanofi and Regeneron Pharmaceuticals), has been approved in adults and is in active study in children and adolescents,” he says.

Researchers are also making strides in pediatric psoriasis armed with increasing knowledge about systemic therapy in children. In fact, biologic agents are being approved in children and adolescents, Dr. Eichenfield says.

“Studies have highlighted comorbidities and the need to (and how to) screen for them in pediatric psoriasis,” he says.

Scientists are learning more about vascular birthmarks and associated localized mutations, paving the way for therapies directed at the underlying mutations.

In epidermolysis bullosa, there exists the potential for cure, according to Dr. Eichenfield.

“The promise of gene therapy to ‘put back in the skin what’s missing genetically’ has played out for a child in Germany with junctional epidermolysis bullosa …,” he says. “This sets the path for future work on stem cell mediated and gene therapies.”

DERMATOPATHOLOGY

In dermatopathology, the American Joint Committee on Cancer (AJCC) revised the melanoma stage system. There are also new tests and treatments for melanoma  and a rising incidence of syphilis, says Dirk Elston, M.D., Medical University of South Carolina, Charleston, S.C., and past-president of American Society of Dermatopathology.

“Melanoma is one of the most important areas of dermatologic practice,” he says.

A better understanding of gene mutations has led to more accurate diagnosis of melanocytic lesions. For example, the BAP-1 mutation on top of BRAF mutation causes benign Wiesner nevi in families with uveal melanoma. BAP-1 mutation on top of GNAQ or GNA-11 mutation causes blue nevus-like melanoma.

New melanoma treatments are more targeted, with tests that determine which treatment will work best for an individual patient. “We have new treatments that work for disease that used to be untreatable,” Dr. Elston says.

DISCLOSURES

Dr. Butterwick is an investigator and advisor for Allergan; an advisor for Colorescience, Galderma Laboratories, Merz Pharmaceuticals and Revance Therapeutics, as well as is a consultant for ThermiAesthetics and Valeant Pharmaceuticals International.

Dr. Lebwohl is an employee of Mount Sinai which receives research funds from: Abbvie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen / Johnson & Johnson, Kadmon, Medimmune/Astra Zeneca, Novartis, Pfizer, Valeant and ViDac. Dr. Lebwohl also is a consultant for Allergan, Aqua Leo-pharma and Promius.

Dr. Eichenfield is a consultant and investigator for Allergan, LEO Pharma, Novan, Sanofi/Regeneron and Galderma Laboratories; a consultant for Anacor Pharmaceuticals, Cutanea Life Sciences, Dr. Reddy, DS Laboratories, Genetech, Lilly ICOS, Medimetriks Pharmaceuticals, Otsuka Pharmaceutical Co., Pfizer, Ralexar Therapeutics, Tioga Pharmaceuticals, TopMD and Valeant Pharmaceuticals International. Dr. Eichenfield is an investigator with Kimberly Clark and Valeant Pharmaceuticals North America.

REFERENCE

“S067 - What's New in Dermatology,” American Academy of Dermatology 2018 annual meeting. Lebwohl, Tomeck, et al. 8-10 a.m., Tuesday, Feb. 20.