Linda Stocum

The FDA issued a Complete Response Letter (CRL) to UCB regarding its Biologics License Application (BLA) for bimekizumab (Bimzelx, UCB), a potential treatment of adults with moderate to severe plaque psoriasis.

In the letter, the FDA states it cannot approve the BLA in its current form. Certain pre-approval inspection observations made during the approval process need resolved before going forward, according to the press release. “We are cooperating with the FDA and are working to address these observations as expeditiously as possible,” UCB stated.

This comes after the FDA’s approval of the biologic was delayed in 2021. The interleukin (IL)-17 inhibitor for plaque psoriasis and psoriatic arthritis blocks IL-17 A and IL-17 F cytokines.

This article originally appeared on Dermatology Times.

Update on US FDA review of biologics license application (BLA) for bimekizumab | UCB. Accessed May 16, 2022. 

https://www.ucb.com/stories-media/Press-Releases/article/Update-on-US-FDA-Review-of-Biologics-License-Application-BLA-for-bimekizumab-0

Articles

UCB announced the FDA issued a CRL that stated that the FDA cannot approve the BLA in its current form.

Bimekizumab Fails to Pass FDA Pre-Approval Inspection

Vitiligo’s cause is unknown, but its detrimental effect on patients’ quality of life is clear.1 Medications for this skin disease may work slower than patients anticipate, causing them to feel hopeless, according to Pearl E. Grimes, MD, FAAD, a clinical professor of dermatology at the David Geffen School of Medicine at UCLA and founder and director of the Vitiligo and Pigmentation Institute of Southern California in Los Angeles.

Discouraged patients may give up and quit treatment, creating tension in their relationship with their physician, Grimes continued. “So many patients that I see come in with the mindset that there is going to be a quick fix for vitiligo. When they don’t see changes in perhaps 2 weeks or 4 weeks, they abandon treatment,” she said.

But the future—possibly the very near future—holds promise. Treatments in the pipeline offer quicker results and a relatively safe profile; there’s even hope of one day finding a cure for this disease, said Seemal Desai, MD, FAAD, an assistant professor in the Department of Dermatology at UT Southwestern and founder and director of Innovative Dermatology in Dallas, Texas. But meanwhile, unmet needs remain, Grimes and Desai agreed.

The drugs’ different mechanism of action will tackle inflammation, perhaps by targeting inflammatory cytokine pathways and increasing production of melanocytes, Desai said. “I think the mechanism [of action] helps to explain and [helps us] better understand the pathophysiology of the disease,” he said. Approval of the first such treatment for vitiligo may be imminent: Ruxolitinib cream 1.5% (Opzelura; Incyte), a topical Janise kinase (JAK) inhibitor, initially had a Prescription Drug User Fee Act (PDUFA) date of April 18, 2022, but has since been extended 3 months to July 18, 2022.2,3

Patients who have active unstable disease or chronic and refractory disease or have head and neck involvement are ideal candidates for the new medications. Desai emphasized that these treatments, especially JAK inhibitors, are meant for specific disease states. “These aren’t going to be the type of product in...a 1-pound jar that patients can slather [on from] head to toe,” he said. Instead, they are meant to be used in conjunction with other therapies such as oral antioxidants, systemic steroids, and narrow-band UV-B for targeted phototherapy. Grimes agreed with Desai’s comments, adding that she does not think ruxolitinib 1.5% cream will replace current treatments, which, when used in combination—particularly for lesions on the face and neck—do work.

The issue, she continued, is how the role of existing treatments might change. “My guess is that we will use these drugs as a primary and as a secondary approach,” Grimes said. Other treatments on the horizon are IL-15 and CXCL10 blockades and other more selective JAK inhibitors, such as TYK and TEC inhibitors, Desai said.4,5

The broadening treatment horizon raises a burning question: Will these treatments be affordable and accessible? Grimes said the drugs have the potential to be expensive and, if not covered by insurance, cost prohibitive. Many physicians will have to work with insurance carriers to help patients get ruxolitinib covered, she said.

Grimes is hopeful that vitiligo will soon have a robust armamentarium, mirroring that of psoriasis, and shares Desai’s hope of a cure.

For more details, visit dermatologytimes. com, where Grimes and Desai discuss onboarding patients, the risks and rewards of treatments, safety signals to heed when beginning a new regimen, and what the latest in research.

Vitiligo. American Osteopathic College of Dermatology. Accessed April 7, 2022. 

Incyte announces acceptance and priority review of sNDA for ruxolitinib cream (Opzelura) as a treatment for patients with vitiligo. Incyte. Accessed Decem- ber 15, 2021. 

https://investor.incyte.com/press-releases/press-releases/2021/ Incyte-Announces-Acceptance-and-Priority-Review-of-sNDA-for-Ruxolitinib- Cream-Opzelura-as-a-Treatment-for-Patients-with-Vitiligo/default.aspx

FDA extends review of Opzelura for skin condition. Formulary Watch®. March 14, 2022. Accessed April 19, 2022. 

https://www.formularywatch.com/view/ fda-extends-review-of-opzelura-for-skin-condition

Evaluation of Amg 714 for Vitiligo (REVEAL). ClinicalTrials.gov. Updated November 1, 2021. Accessed April 6, 2022. 

https://clinicaltrials.gov/ct2/show/ NCT04338581

Rashighi M, Agarwal P, Richmond JM, et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. 

. 2014;6(223):223ra23. doi:10.1126/scitranslmed.3007811

Ruxolitinib cream 1.5% may soon be the first FDA-approved treatment for repigmentation of vitiligo. Experts share what dermatologists need to know regarding efficacy, safety, and cost of this topical drug.

The Drug Pipeline for Vitiligo

In a survey of more than 1000 Americans, the American Academy of Dermatology (AAD) has found that although Americans believe that sun protection is important, many lack the knowledge to properly protect themselves.

Other results include, 62% of responders rating themselves an overall grade of excellent or good for sun protection in 2021, but 63% reported getting a tan, which is an increase of 9% from 2020. About 30% of survey takers reported getting a sunburn, which is an increase from 25% in 2020.

“If you are getting a tan, you are definitely not doing a good job of protecting yourself from the sun,” said board-certified dermatologist Mark D. Kaufmann MD, FAAD, president of the AAD, in the release. “There is no such thing as a safe tan. Every time you tan or burn, you are also damaging the DNA in your skin. The more you damage your DNA, the greater your risk of getting skin cancer.”

Other misconceptions the survey found were:

Responders believing that SPF 30 is twice as protective as SPF 15 (67%)

Often forgetting to reapply sunscreen (65%)

Unaware that shade protects a person from UV rays (43%)

Patients understanding the difference between SPF numbers and what the measures mean is an essential part of sun protection. The AAD recommends that everyone, in order to reduce the risk of skin cancer, should seek shade, wear sun-protective clothing, and apply a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher.

“It’s great that 82% of respondents say protecting their skin from the sun is more important to them now than it was five years ago,” said Kaufmann in the release. “However, it’s important that people use sun protection now so they can prevent premature skin aging and reduce their risk of skin cancer before they start seeing the damaging effects of the sun on their skin.”

As a way to help educated the public, the AAD will be starting its SPOT Skin Cancer campaign on May 2nd, Melanoma Monday, as May is melanoma awareness month. The Academy has also awarded 20 shade structure grants to public schools and non-profit organizations this year for the installation of permanent shade structures for outdoor locations that are not protected from the sun, such as playgrounds, pools, or recreation spaces, according to the release. Since the start of the Shade Structure Grant program in 1999, the Academy has awarded 480 shade structure grants that protect an estimated 3.6 million people from overexposure to the sun each day. The AAD also has a youth education program called the Good Skin Knowledge, that teaches common skin, hair, and nail conditions to children and adolescence.

“As we head into summer, it’s important that the public practices safe sun to reduce their risk of skin cancer,” Kaufmann concluded. “If you have any questions about how to protect yourself from the sun or notice new or suspicious spots on your skin or any spots that are changing, itching or bleeding, make an appointment to see a board-certified dermatologist.”

New American Academy of Dermatology survey reveals most Americans say sun protection is more important now than five years ago, yet many misunderstand how to protect themselves. April 26, 2022. Accessed April 28, 2022. 

https://www.aad.org/news/new-aad-survey-reveals-growing-importance-sun-protection

An American Academy of Dermatology survey found that more Americans say sun protection is more important than 5 years ago, but don’t understand how to protect themselves. 

Survey: Misunderstanding Sun Protection is a Common Problem

With the end of rosacea awareness month nearing, Sol-Gel Technologies and Galderma have announced the approval of their 5% encapsulated benzoyl peroxide (E-BPO) cream (Epsolay; Sol-Gel Technologies Ltd and Galderma) for the treatment of inflammatory lesions of rosacea (papulopustular rosacea or PPR) in adult patients.

 Sol-Gel has granted to Galderma the exclusive rights to commercialize the 5% E-BPO cream in the United States.

The New Drug Application (NDA) for the product was filed back in 2020, with a Prescription Drug User Fee Act (PDUFA) date for the FDA to make a decision on Epsolay is set for April 26, 2021 but was delayed due to the pandemic.

 This product uses Sol Gel’s patented microencapsulation technology that creates a barrier between the skin and the dose. The technology aims to reduce the risk of benzoyl peroxide’s oxidative effect which can cause skin irritation.

The approval was based on 2 positive, identical phase 3 randomized, double-blind, multicenter, 12-week, clinical trials. Both trials evaluated the safety and efficacy of the 5% E-BPO cream compared to vehicle in 733 patients with inflammatory lesions of rosacea. Both trials had the coprimary endpoints of the proportion of patients with treatment success and the absolute change from baseline in lesion counts at week 12.

It was found that the 5% E-BPO cream demonstrated great efficacy than the vehicle cream in both endpoints starting from 4 weeks of treatment in both trials. With E-BPO cream treatment, inflammatory lesions of rosacea were reduced by nearly 70% by the end of both 12-week trials vs. 38-46% with vehicle, according to the press release. Additionally, almost 50% of patients achieved an Investigators Global Assessment (IGA) of 0/1 at 12 weeks compared to 38%-46% with placebo. At week 2, a post-hoc analysis of the lesion count and IGA success confirmed, a significantly greater treatment effect for the 5% E-BPO relative to vehicle. In the open-label extension, 73% of patients were IGA 1/0 at 52 weeks.

“Having Epsolay approved by the FDA is a watershed moment for the 16 million people in the United States suffering from rosacea,” stated Alon Seri-Levy, PhD, Chief Executive Officer of Sol-Gel, in the press release. “Based on the robust clinical data, we believe that Epsolay has the potential to change the treatment landscape. We are proud to have Galderma as our partner to launch this drug since Galderma has an unparalleled track record of introducing innovative drugs in the United States’ rosacea market,” said Dr. Seri-Levy.

Neal D. Bhatia. MD, dermatologist at Therapeutics Clinical Research in San Diego, California, said in the press release, “There is poor adherence of my patients to current treatments for inflammatory rosacea and I look forward to being able to prescribe Epsolay to them, primarily because Epsolay has demonstrated outstanding and rapid efficacy results and also because Epsolay has been shown to be well-tolerated, both of which are important factors to ensure patients' satisfaction.”

Sol-gel technologies and galderma announce fda approval of epsolay®. GlobeNewswire News Room. Published April 25, 2022. Accessed April 28, 2022. 

https://www.globenewswire.com/news-release/2022/04/25/2427977/0/en/Sol-Gel-Technologies-and-Galderma-Announce-FDA-Approval-of-EPSOLAY.html

Sol-Gel Technologies Announces FDA Acceptance for Filing of New Drug Application for Epsolay® for the Treatment of Inflammatory Lesions of Rosacea: Sol-Gel. (2020, September 10). Retrieved September 14, 2020, from 

https://ir.sol-gel.com/news-releases/news-release-details/sol-gel-technologies-announces-fda-acceptance-filing-new-drug

Sol-Gel Technologies and Galderma announced the FDA approval of the 5% benzoyl peroxide, cream for the treatment of inflammatory lesions of rosacea.

FDA Approves Epsolay for Inflammatory Lesions of Rosacea

Investigators in a poster presentation from the 2022 American Academy of Dermatology Annual Meeting created an observational, real practice study, to analyze real world data on the efficacy and safety of dupilumab (Dupixent; Sanofi and Regeneron Pharmaceuticals) in atopic dermatitis (AD) patients 16 years and older.

Dupilumab is a fully human IgG4 monoclonal antibody against interleukin (IL)-4 receptor IL-13 pathways and is not an immunosuppressant.

This study was conducted from January 2020 to August of 2021 and included patients that had moderate to severe AD, were 16 years or older, had an Eczema Area and Severity index (EASI) score of greater than or equal to 21, a physician global assessment (PGA) score of greater than or equal to 3, total effected body surface area (BSA) of 10% or more, and a failure to respond to both topical treatment and cyclosporine.

In total 14 patients were included in the study, 8 of which were male, the mean age of the group was 30.5 years with patients being anywhere being between the ages of 16 and 57. The group also had a mean basal EASI score of 31.4 +/- 8.3 before treatment had begun. After 16 weeks of treatment, this score dropped significantly, with the mean EASI score being 6.4 +/- 3.5, with an overall mean improvement of 76.3%. When broken down further, the data demonstrated that there was an EASI 50 improvement in all the patients, EASI 75 improvement in 64% of patients, and EASI 90 in 21% of them.

At 24 weeks of dupilumab treatment, the mean EASI improvement increased from 16 weeks to 89.6% and the patients who experience EASI 50, EASI 75, and EASI 90 were 100%, 100%, and 60% respectively. The researchers stated that they observed a rapid reduction in pruritus mean during this time also.

When it comes to adverse events (AEs), the most common were conjunctivitis and facial erythema—both occurring in 14% of patients. The poster stated that they were limited by being a, “small monocentric observational study with different evaluators measuring scores.”

Dupilumab recently had its supplemental biologics license application (sBLA) as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable, accepted by the FDA.2 The target action sate for this investigational use is June 9, 2022.

Martinez-Mariscal J, Cabana-Navia R, Martinez-Fernandez A, et al. Real-world experience od dupilumab treatment in atopic dermatitis. Poster. Presented at: 2022 American Academy of Dermatology Annual Meeting, March 25-29, Boston, Massachusetts.

Dupilumab receives FDA priority review and accepts SBLA for children 6 months to 5 years. Dermatology Times. Accessed April 1, 2022. https://www.dermatologytimes.com/view/fda-gives-priority-review-and-accepts-bla-for-dupi

A supplemental biologics license application was recently submitted.

Evaluating Real-World Dupilumab Data

 at the Shanghai Skin Disease Hospital investigated 35 patients with acne vulgaris to determine the potential adverse events (AEs) from treating with5-aminolaevulinic acid photodynamic therapy (ALA-PDT).

The AEs were divided into acute-phase AEs that included erythema (94.3%), post-treatment pain (91.4%), burning skin (91.4%), dry skin (91.4%), itching (85.7%), pustule (82.9%), edema (20%), and blister (11.4%); or recovery-phase AEs, which included crust (65.6%), exudation (48.6%), and hyperpigmentation (42.7%).

The younger the patients were, the more likely to have pustules (P<.05). Additionally, male patients experienced itching more often than female patients (P<.05). Efficacy of ALA-PDT for severe acne was positively related to the severity of acute-phase adverse reactions, the article explained. Out of the AEs, the duration of pain was the shortestwhilecrusting and hyperpigmentation lasted considerably longer.

Overall, the severity of AEs tended to decrease with increased patient age, except for itching, and hyperpigmentation. Lighttomoderate AEscould be the inflammatory reactions of ALA-PDT, predicting a good efficacy, the authors said.

“A form for evaluation of AEs based on the present study could assist dermatologists in predicting and managing AEs for greater efficacy and higher patient satisfaction,” the authors concluded.

Lei S, Yang J, Zhang L, et al. A prospective study of adverse reactions of ALA-PDT for acne vulgaris. PhotodiagnosisPhotodynTher. Published online February 14, 2022:102752. doi:10.1016/j.pdpdt.2022.102752

A recent study investigated the potential adverse events around using 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) for acne treatment. 