Linda Stocum

The FDA has approved dupilumab (Dupixent; Sanofi and Regeneron Pharmaceuticals, Inc) 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, according to a press release. This filing is also under review by the European Medicines Agency (EMA) for this age group along with and submissions to regulatory authorities in other countries worldwide. Dupilumab is a fully human monoclonal antibody that inhibits the signaling of the interleukin (IL)-4 and IL-13 pathways and is not an immunosuppressant.

The president and CRO of the National Eczema Association, Julie Block, commented on the approval and said, “moderate-to-severe atopic dermatitis in babies and young children is more than just a rash – the intense itch can make them scratch uncontrollably throughout the day and night and cause their skin to crack and bleed.” She continued, “caregivers do their best to manage skincare routines multiple times a day, but for many, topical treatments are not enough. We’re pleased to see how scientific innovation and research continues to address unmet needs for the atopic dermatitis community, and we’re hopeful for the positive impact Dupixent can have for these children and their families."

Most patients, 85%-90%, first have AD symptoms before the age of 5 years, which often affect them into the later years of their lives.

Dupilumab submitted for priority review from the FDA, which was accepted in February 2022, and had an original target action date of June 9, 2022.

The approval was supported by data from the LIBERTY AD trial (NCT03346434), a phase 3 trial evaluating dupilumab every 4 weeks (200 mg or 300 mg, based on body weight) plus low-potency topical corticosteroids (TCS) or TCS alone (placebo) in pediatric patients aged 6 months to 5 years with uncontrolled moderate to severe AD. The trial met all primary and secondary endpoints.

The analysis found that at 16 weeks patients treated with dupilumab:2

Twenty eight percent achieved clear or almost-clear skin compared to 4% with placebo;

fifty three percent achieved 75% or greater overall disease improvement from baseline compared to 11% with placebo;

seventy percent average improvement from baseline in EASI 75 compared to 20% improvement with placebo;

forty nine percent average improvement from baseline in itch compared to 2% improvement with placebo; and

significantly improved measures of observed patient outcomes (including sleep, skin pain and health-related quality of life), as well as caregiver-reported health-related quality of life.

The data found that the safety profile in this trial was like the safety profile in patients 6 years and older with AD. The long-term (52 weeks) safety profile of patients receiving active treatment found it was also consistent. The most common adverse event was hand-foot-and-mouth disease and skin papilloma reported in 5% and 2% of patients treated with dupilumab aged 6 months to 5 years, respectively, and none of these cases led to treatment discontinuation.

“This approval is a tremendous advancement for children as young as six months old with moderate-to-severe atopic dermatitis, as there is a large unmet need in this population and we’ve seen what Dupixent can do for older children and adults with this disease,” said Mercedes E. Gonzalez, MD, FAAD, pediatric dermatologist at Pediatric Dermatology of Miami. “Dupixent is a very welcome addition to our treatment options, which up until recently, primarily included potent topical steroids. Now we have something that targets an underlying cause of the disease, and may change the trajectory of their childhood by removing the burden of moderate to severe eczema from their lives, hopefully making the future brighter for these children.”

This article originally appeared on Dermatology Times.

Press Release: FDA approves Dupixent® (Dupilumab) as first biologic medicine for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. GlobeNewswire News Room. Published July 6, 2022. Accessed June 8, 2022. 

https://www.globenewswire.com/news-release/2022/06/07/2458243/0/en/Press-Release-FDA-approves-Dupixent-dupilumab-as-first-biologic-medicine-for-children-aged-6-months-to-5-years-with-moderate-to-severe-atopic-dermatitis.html

Articles

Sanofi and Regeneron Pharmaceuticals, Inc announced the FDA approval of dupilumab. It is now the first biologic medicine for children from 6 months to 5 years old with moderate to severe atopic dermatitis.

FDA Approves Dupilumab for Atopic Dermatitis in Children 6 Months to 5 Years

The news of Sanofi selling the rights of pembrolizumab (Libtayo; Sanofi and Regeneron Pharmaceuticals, Inc) comes after a restructuring of an oncology collaboration agreement between the companies which was created in 2015. Under the amended and restated license and collaboration agreement, Regeneron will obtain worldwide exclusive license rights to Libtayo, according to the press release.

Before this, the companies split the profits from the worldwide operations equally co-commercialized pembrolizumab in the United States. Sanofi was responsible for commercialization across the rest of the globe by itself.

“Our diverse oncology portfolio doubled between 2019 and 2022 and now includes twelve compounds in clinical trials, each with a unique mechanism of action. Our early steps with Libtayo in immuno-oncology provided a strong foundation for our revitalized oncology efforts,” said Bill Sibold, the executive vice president of Specialty Care & president of North America for Sanofi in a press release. “Now, we are focused on leveraging our internal capabilities and advancing a new generation of oncology medicines. We continue to maintain a strong partnership with Regeneron in immunology, and will work closely with them on the seamless transition of Libtayo to ensure there is no impact for patients.”

In the terms of the amended and restated immuno-oncology license and collaboration agreement, Sanofi will transfer the rights to develop, commercialize, and manufacture pembrolizumab entirely to Regeneron, on a global scale. This transition over the course of a period which will be defined by the requirement of each government and their clearances needed worldwide.

Sanofi, in exchange for these rights, will receive an upfront payment of $900 million, and an 11% royalty on global net sales of pembrolizumab, according to the release. There will also be a payment of $100 million to Sanofi in the case of a regulatory milestone payment approval for pembrolizumab in combination with chemotherapy for first-line treatment of certain patients with non-small cell lung cancer treatment (NSCLC) by either the FDA or European Commission. In addition, there may be sales-related milestone payments of up to $100 million in total over the next 2 years. The transaction is subject to clearance under competition law and is expected to close in the third quarter of 2022.

Regeneron will also accelerate reimbursement of the development balance associated with Regeneron and Sanofi’s separate Antibody Collaboration, the press release continued. The company, Regeneron, will increase from its share of profits from 10% to 20 to Sanofi to reimburse Sanofi-funded development expenses. It will stay that way until Regeneron’s share of the total cumulative development costs incurred under the collaboration has been reached.

This article was originally published by Dermatology Times.

Regeneron buys Sanofi cancer drug for up to $1. 1 billion. Accessed June 2, 2022. https://finance.yahoo.com/news/regeneron-buys-sanofi-cancer-drug-134521034.html

Regeneron Pharmaceuticals Inc came to an agreement to buy the drug from Sanofi for up to $1.1 billion.

Regeneron Buys Rights to Pembrolizumab from Sanofi

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.

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

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.