A Topical Treatment Revolution is on the Horizon for Psoriasis
Topical steroids have remained a mainstay first-line treatment for psoriasis, but two new drugs in development aim to revolutionize how topical drugs are used in treatment of the disease.
“We’ve had a decent amount of minor innovation in psoriasis,” Mark G. Lebwohl, MD, dean for clinical therapeutics and chair emeritus of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai, said. “One thing that has troubled many of us is that we don’t like to use steroids on the face or intertriginous sites. The problem is the current nonsteroids are not as strong or effective as the strong steroids. But now we have two drugs coming which are about as effective as the moderately potent or even the potent steroids.”
The two new drugs — which have both completed phase 3 trials — are tapinarof (Dermavant Sciences), an aryl hydrocarbon receptor modulating agent, and roflumilast (Arcutis Biotherapeutics), a phosphodiesterase type 4 inhibitor.
“We are getting two new chemical entities, which is really exciting in dermatology because it doesn’t happen that often, especially in the topical world,” Leon H. Kircik, MD, clinical professor of dermatology at Icahn School of Medicine at Mount Sinai and Indiana University Medical Center, as well as medical director for Physicians Skin Care PLLC, DermResearch PLLC and Skin Sciences PLLC, said.
“Tapinarof is an aryl hydrocarbon receptor modulating agent, which essentially works by a few well-known mechanisms of action, but the prominent one is the down regulation of expression of interleukin-17, which we all appreciate as a pivotal cytokine in psoriasis pathophysiology,” Bruce E. Strober, MD, PhD, clinical professor of dermatology at Yale University School of Medicine, said.
Dermavant’s phase 3 PSOARING clinical trials included PSOARING 1 and PSOARING 2 — identical, multicenter, double-blind, vehicle-controlled, randomized trials that randomly assigned 510 and 515 patients, respectively, to receive once-daily tapinarof cream 1% or vehicle cream for 12 weeks.
A Physician Global Assessment score of clear or almost clear (0 or 1), with at least a 2-grade improvement from baseline, was found in 35.4% and 40.2% of patients treated with tapinarof, compared with 6% and 6.3% of those treated with vehicle. Additionally, interim analysis of the PSOARING 3 long-term, open label trial has also found results to continue with long-term use.
A New Drug Application has been accepted by the FDA for tapinarof and a Prescription Drug User Fee Act date is expected in mid-2022.
Roflumilast is not the first PD4 inhibitor to enter the dermatology world. Crisaborole (Eucrisa, Pfizer) is a topical treatment for atopic dermatitis, and apremilast (Otezla, Amgen) is an oral PD4 inhibitor approved for psoriasis and psoriatic arthritis.
“Eucrisa doesn’t have the best reputation because of the lack of efficacy, so roflumilast is coming with a little bit of baggage,” Kircik said. “On the other hand, it has shown that it’s almost 30 times more potent than the existing PD4 inhibitor, so that’s very promising.”
The phase 3 DERMIS-1 and DERMIS-2 trials — two identical randomized, double-blind, vehicle-controlled studies — evaluated the efficacy of once-daily roflumilast cream 0.3% in plaque psoriasis patients compared with vehicle.
Results from the two trials, showing robust efficacy of roflumilast, were presented at the 2021 European Academy of Dermatology and Venereology Congress virtual meeting.
At week 8, Investigator Global Assessment scores of clear or almost clear (0 or 1) were reported in 42.4% and 37.5% of roflumilast-treated patients compared with 6.1% and 6.8% of vehicle-treated patients.
“Additionally, roflumilast has separately evaluated data of exactly the areas we worry about — the intertriginous areas — and they have found an even higher degree of clearance,” Lebwohl said. “We’re looking at 90% of patients achieving clear or almost clear in intertriginous areas.”
Roflumilast is also in trials as a foam formulation, which will make it more useful for hair-bearing areas of the body.
A New Drug Application for roflumilast cream was submitted to the FDA in October 2021.
A boost to the topical armamentarium
Current topical drugs may have greater efficacy than what these new formulations have shown; however they do have some downsides, according to Strober.
“The mainstay of topical therapy for psoriasis is topical steroids, which are effective,” he said. “But there are some side effects at the application area if they are overused, and secondly, topical steroids have a tendency to stop working over time.”
Tapinarof and roflumilast will give clinicians options and could tackle other aspects of the disease.
“These allow us to address the problem from different perspectives with different mechanisms of action,” Kircik said. “Not everyone is going to respond to a drug in the same mechanism of action, so it’s good to have specific targets. If one doesn’t work, then the other will, unlike the topical steroids that are nonspecific anti-inflammatories.”
Who will benefit?
Recognizing that every psoriasis patient will most likely need some form of topical therapy emphasizes the need for multiple options.
“We don’t have any one drug that gets 100% of patients clear 100% of the time,” said Linda F. Stein Gold, MD, director of dermatology clinical research at Henry Ford Health System. “Some patients have localized disease that can be managed by topical therapy alone. Others have more widespread disease that is managed by systemic agents but may have a few residual areas that can be treated with topical agents.”
For patients with less than 10% body surface area psoriasis, topical therapy may very well be the only therapy prescribed, according to Stein Gold. And for those who have more severe disease and are on biologic therapies, topical therapies will also often be needed to clear any residual plaques.
“The efficacy of biologics is measured in numbers like [Psoriasis Area and Severity Index (PASI)]-75 or PASI-90, but that means there is still 25% or 10% leftover,” Lebwohl said. “So those patients end up being some of our biggest users of topical therapy, because they need both in order to clear.”
Challenges to topical therapy
Topical therapies for any condition come with their own challenges, and in psoriasis treatment the two biggest difficulties are patient adherence and insurance coverage.
Some of the vehicles used in topical therapies can be greasy and thick and patients often have a tendency not to adhere to their treatment regimens; however the newer cream or foam formulations have the potential to address that problem. Areas with hair are the biggest difficulty, as well as when a patient needs the treatment on large body surface areas.
“The biggest challenge is patient compliance. The newer, cosmetically elegant vehicles are easier to apply and may be easier to use,” Stein Gold said.
To increase adherence, she recommends patients take baseline photos of lesions and document the progress to show how the therapy is helping over time. Additionally, products that can be used once a day, preferably at night, will have better adherence than those that need to be used twice a day.
“I give my patients a realistic timeline as to when to expect to see improvement,” she added.
Difficulty in obtaining insurance coverage for these drugs is not something unique to psoriasis medications. This remains a challenge for all drugs — especially drugs that are new to the market.
“Most of the time third-party payers want you to use a generic steroid, and sometimes even generic steroids are not covered,” Kircik said. “In order to get these branded products, it can be an uphill battle for patients.”
As tapinarof and roflumilast potentially make their way to the market, they have the opportunity to change how psoriasis is treated topically for millions of patients.
“We have two nonsteroids on the horizon that are highly effective and don’t have any of the drawbacks of some of the other drugs we’ve used,” Lebwohl said. “I would urge clinicians, if they want to have a good experience prescribing the drugs to their patients, to make sure to identify a pharmacy that honors the pharmaceutical company’s discounted price.”
- Dermavant reports positive phase 3 results for tapinarof cream in adult patients with plaque psoriasis. https://www.dermavant.com/dermavant-reports-positive-phase-3-results-for-tapinarof-cream-in-adult-patients-with-plaque-psoriasis/. Published Aug. 26, 2020. Accessed Nov. 22, 2022.
- Positive data from PSOARING 3 support long-term use of tapinarof cream in adults with plaque psoriasis, with durable (on-therapy) and remittive (off-therapy) benefits. https://www.dermavant.com/positive-data-from-psoaring-3-support-long-term-use-of-tapinarof-cream-in-adults-with-plaque-psoriasis-with-durable-on-therapy-and-remittive-off-therapy-benefits/. Published Feb. 18, 2021. Accessed Nov. 22, 2021.
- Dermavant announces FDA acceptance for filing of new drug application (NDA) for tapinarof cream for the treatment of adults with plaque psoriasis. https://www.dermavant.com/dermavant-announces-fda-acceptance-for-filing-of-new-drug-application-nda-for-tapinarof-cream/. Published Aug. 10, 2021. Accessed Nov. 22, 2021.
- Lebwohl MG, et al. Roflumilast cream, a once-daily, potent phosphodiesterase-4 inhibitor, in chronic plaque psoriasis patients: Efficacy and safety from DERMIS-1 and DERMIS-2 phase 3 trials. Presented at: European Academy of Dermatology and Venereology meeting; Sept. 29-Oct. 2, 2021 (virtual meeting).
- Arcutis submits topical roflumilast cream new drug application to FDA for the treatment of adults and adolescents with plaque psoriasis. https://www.arcutis.com/arcutis-submits-topical-roflumilast-cream-new-drug-application-to-fda-for-the-treatment-of-adults-and-adolescents-with-plaque-psoriasis/. Published Oct. 4, 2021. Accessed Nov. 22, 2021.
- For more information:
- Leon H. Kircik, MD, can be reached at 1169 Eastern Parkway #2310, Louisville, KY 40217; email: email@example.com.
- Mark G. Lebwohl, MD, can be reached at 5 98th St. 5th Floor, New York, NY 10029; email: firstname.lastname@example.org.
- Linda F. Stein Gold, MD, can be reached at 6530 Farmington Road, Suite 101, West Bloomfield Township, MI 48322; email: email@example.com.
- Bruce E. Strober, MD, PhD, can be reached at 1 Willowbrook Road, Cromwell, CT 06417; email: firstname.lastname@example.org.