Kaitlyn Bader

Results from Timber Pharmaceuticals’ phase 2b CONTROL study of TMB-001, a topical isotretinoin to treat moderate-to-severe congenital ichthyosis (CI), were published in the 

Journal of the American Academy of Dermatology

 Timber Pharmaceuticals is a biopharmaceutical company that develops therapies for rare and orphan dermatologic diseases.

 showed that in the per protocol (PP) population, 100%, 40%, and 40% of patients who received TMB-001 0.05%, TMB-001 0.1%, and vehicle achieved the primary endpoint, which was a 50% reduction in the Visual Index for Ichthyosis Severity (VIIS) scale score (or VIIS-50) versus baseline (P= 0.04 for TMB-001 0.05% vs. vehicle). In the intent-to-treat (ITT) population, 64%, 40%, and 33% of patients who received TMB-001 0.05%, TMB-001 0.1%, and vehicle achieved VIIS-50 (P = 0.17 for TMB-001 0.05% vs. vehicle).

The secondary efficacy endpoint measured the difference in the percentage of patients who achieved Investigator Global Assessment (IGA) treatment success (≥2-grade reduction in scaling and fissuring severity over all treated areas of the body) comparing TMB-001 to vehicle. In the PP population, 100%, 60%, and 10% of patients who received TMB-001 0.05%, TMB-001 0.1%, and vehicle reported a ≥2-grade IGA score improvement (P= 0.002 for TMB-001 0.05% vs vehicle). In the ITT population, improvement of ≥2-grade IGA score was observed in 55%, 40%, and 8% of patients who received TMB-001 0.05%, TMB-001 0.1%, and vehicle (P= 0.02 for TMB-001 0.05% vs vehicle).

The randomized, parallel, double-blind, vehicle-controlled phase 2b CONTROL study evaluated the efficacy and safety of 2 concentrations of TMB-001 in patients with X-linked recessive (XLRI) or autosomal recessive lamellar (ARCI-LI) subtypes of CI. In total, 33 patients were randomly selected to receive either TMB-001 0.05%, TMB-001 0.1%, or vehicle 2 times a day, layered with CI subtype, for 12 weeks. The ITT population included all patients initially enrolled in the trial, and the PP population included all patients who completed the total 12 weeks of treatment. Patient-reported adverse events include local skin reactions that were mild to moderate. No serious adverse events have been reported.

Timber Pharmaceuticals has announced the initiation of the pivotal phase 3 ASCEND study to evaluate the efficacy, safety, and pharmacokinetics of TMB-001 0.05% for the treatment of moderate-to-severe forms of CI in patients aged 6 years or older.

CI affects approximately 80,000 people in the US and leads to cutaneous manifestations of large, dark scaling throughout the body.

This article originally appeared on Dermatology Times.

Timber pharmaceuticals announces publication of results from phase 2b control study of FDA-designated breakthrough therapy TMB-001 in the 

. GlobeNewswire News Room. Published August 26, 2022. Accessed August 26, 2022. 

https://www.globenewswire.com/news-release/2022/08/26/2505296/0/en/Timber-Pharmaceuticals-Announces-Publication-of-Results-from-Phase-2b-CONTROL-Study-of-FDA-Designated-Breakthrough-Therapy-TMB-001-in-the-Journal-of-the-American-Academy-of-Dermato.html

Teng J, Bunick C, et al. The CONTROL study: A randomized, double-blind vehicle-controlled phase 2b study of novel topical isotretinoin formulation demonstrates improvement in recessive X-linked and autosomal recessive lamellar congenital ichthyosis. 

. Published online July 20, 2022. doi:10.1016/j.jaad.2022.07.028

Articles

Timber Pharmaceuticals’ CONTROL study evaluated the safety and efficacy of the topical isotretinoin.

Congenital Ichthyosis Treatment TMB-001 Yields Positive Results in 2b Trial

The US Food and Drug Administration (FDA) has approved ustekinumab (Stellara; Janssen Pharmaceutical) for the treatment of active psoriatic arthritis (PsA) in pediatric patients. Ustekinumab is the first and only biologic that targets both cytokines interleukin (IL)-12 and IL-23.

 PsA is a rare disease that mimics adult PsA and affects 5%-8% of children and adolescents that suffer from chronic inflammatory arthritis.

Since the first approval for adults with moderate to severe PsA in 2009, 2 out of the 4 indications for ustekinumab now include pediatric patients to further expand its treatment reach. Ustekinumab is a fully monoclonal antibody that selectively inhibits interleukin (IL)-12 and IL-23. Medical professionals recognize that both cytokines are important to calm down the overactive inflammatory response in many autoimmune diseases.

Ustekinumab is injected subcutaneously 4 times per year after 2 initial starter doses. The approval is based on pharmacokinetic (PK) data and the conclusion of the efficacy and safety of ustekinumab in multiple phase 3 studies in adult and pediatric patients with moderate to severe plaque psoriasis (PsO) (PSTELLAR, CADMUS, and CADMUS Jr) and adult patients with active PsA (PSUMMIT I and II). Data showed that PK exposure of ustekinumab in pediatric PsO patients with active PsA was consistent with phase 3 clinical trials of ustekinumab in pediatric PsO patients without active PsA, as well as with adult patients with moderate to severe PsO or adult patients with active PsA. Data on similar efficacy endpoints were similar in the pediatric PsO patients with active PsA.

Symptoms of pediatric PsA include joint inflammation and skin lesions. Overall, pediatric PsA is difficult to treat and needs a standardized treatment option. Some common adverse events of ustekinumab include nasal congestion, sore throat, runny nose, headache, itching, stomach pain, and joint pain.

Johnson JPC of J&J. Stelara (Ustekinumab) approved by the US food and drug administration to treat pediatric patients with active psoriatic arthritis. Accessed August 1, 2022. 

https://www.prnewswire.com/news-releases/stelara-ustekinumab-approved-by-the-us-food-and-drug-administration-to-treat-pediatric-patients-with-active-psoriatic-arthritis-301596940.html

Janssen Pharmaceutical Companies of Johnson & Johnson announced the approval of ustekinumab as a new treatment option for patients aged 6 years or older with active psoriatic arthritis.

FDA Approves Ustekinumab for Treating Psoriatic Arthritis in Children

The FDA has approved roflumilast (Zorvye; Arcutis Biotherapeutics) cream 0.3% for the treatment of plaque psoriasis in adolescents and adults. This novel drug is the first and only topical phosphodiesterase-4 (PDE4) inhibitor approved for the treatment of plaque psoriasis. Roflumilast cream provides fast clearance of psoriasis plaques while also reducing itch across affected parts of the body.

Roflumilast cream is approved to treat varying degrees of plaque psoriasis, including mild, moderate, and severe, with no limitations on the duration of use. The steroid-free cream should be applied once-daily to the affected areas for both treatment and relief. Arcutis Biotherapeutics reported in the press release1 that the cream is a safe and well-tolerated formulation that is uniquely formulated to simplify disease management for patients with plaque psoriasis.

"We are very excited to have a new non-steroidal topical agent to help us manage our psoriasis patients with the recent approval of roflumilast cream 0.3%. It is incredible to see the evolution in therapies for psoriasis, and the expansion of therapies for topical treatment is especially important to help manage the large set of patients who might not need systemic therapies," said Lawrence Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego and professor of dermatology and pediatrics and vice-chair of the department of dermatology at UC San Diego School of Medicine in California. "My psoriasis teens and young adults are diverse in many ways and in their disease manifestations; I look forward to using Roflumilast to help minimize their disease and its impact on their lives.”

Approximately 9 million people in the United States suffer from plaque psoriasis, including adolescents and adults.

 Topical therapies have typically been the primary treatment option for plaque psoriasis, but determining a treatment plan has not always been easy. Plaque psoriasis affects different parts of the body, including areas like the face, elbows, knees, genitalia, and other areas of skin-to-skin contact. With varying degrees of skin sensitivities in each area, some cases require multiple topical medication prescriptions which can become complicated and frustrating.

Roflumilast cream was proven to be safe and effective in all hard-to-treat areas, making it a promising steroid-free option for both dermatologists and their patients. The approval is based on data from the pivotal DERMIS-1 and DERMIS-2 phase 3 studies. According to the press release, roflumilast cream improved the severity and impact of itch as early as week 2. Two-thirds of patients with a Worst Itch-Numerical Rating Score (WI-NRS) of 4 or higher at baseline achieved a > 4-point reduction in itch at week 8. Roflumilast is the only topical treatment for which efficacy has been specifically demonstrated in the treatment of intertriginous psoriasis, as measured by Intertriginous IGA (I-IGA) Success (72% vs. 14% in DERMIS-1 and 68% vs. 17% in DERMIS-2 at Week 8 [P<0.0001]).1

A few common adverse events include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection.

This article originally appear on Dermatology Times.

McCulloch T. FDA approves arcutis’ zoryve (roflumilast) cream 0. 3% for the treatment of plaque psoriasis in individuals age 12 and older. Arcutis Biotherapeutics. Published July 29, 2022. Accessed July 29, 2022. 

https://www.arcutis.com/fda-approves-arcutis-zoryve-roflumilast-cream-0-3-for-the-treatment-of-plaque-psoriasis-in-individuals-age-12-and-older/

Arcutis Biotherapeutics’ roflumilast cream will provide relief to patients aged 12 years or older diagnosed with plaque psoriasis.

Roflumilast Cream 0.3% Approved by FDA for Plaque Psoriasis

Incyte announced the FDA has approved ruxolitinib (Opzelura; Incyte) cream 1.5% as a topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age or older.

 The groundbreaking approval is the only FDA-approved treatment for repigmentation and the only topical formulation of a JAK inhibitor approved in the US. Vitiligo is an autoimmune disease that causes sections of the skin to lose their pigment (color), causing white patches of skin to appear. Melanocytes are attacked and destroyed by the body’s immune system and can occur anywhere in the body.

Ruxolitinib provides relief to patients with nonsegmental vitiligo that had high unmet medical needs and no previously approved therapy options. For the best results, patients should apply ruxolitinib cream twice daily to the affected areas of skin, up to 10% of body surface area. It may take more than 24 weeks for patients using ruxolitinib cream to see satisfactory results.

The approval was based on data from the 

 (TRuE-V1 and TRuE-V2), which evaluated the safety and efficacy of ruxolitinib in over 600 people with nonsegmental vitiligo, aged 12 years and older. Results at week 24 showed that approximately 30% of patients using ruxolitinib achieved ≥75% improvement from baseline in the facial Vitiligo Area Scoring Index (F-VASI75). By Week 52, approximately 50% of patients treated with ruxolitinib achieved F-VASI75.

Common adverse effects of ruxolitinib in people treated for nonsegmental vitiligo include acne at the application site, itching, common cold, headache, urinary tract infection, redness, and fever.

, it was noted that ruxolitinib was previously indicated for atopic dermatitis. Christopher G. Bunick, MD, PhD, Jeffrey Cohen, MD, Linda Stein Gold, MD, and Peter Lio, MD, discussed the safety and efficacy considerations of the topical JAK inhibitor, ruxolitinib.

Incyte announces US FDA approval of opzelura (ruxolitinib) cream for the treatment of vitiligo. Published July 19, 2022. Accessed July 19, 2022. 

https://www.businesswire.com/news/home/20220718005819/en/Incyte-Announces-U.S.-FDA-Approval-of-Opzelura%E2%84%A2-ruxolitinib-Cream-for-the-Treatment-of-Vitiligo

Vitiligo. Yale Medicine. Accessed July 19, 2022. 

https://www.yalemedicine.org/conditions/vitiligo

Ruxolitinib (Opzelura) cream is the first and only FDA-approved treatment for patients with vitiligo. 

FDA Approves Ruxolitinib Cream 1.5% to Treat Nonsegmental Vitiligo  

 from Nutrafol’s Sophia Kogan MD, and Isabelle Raymond PhD in New York, New York, and Glynis Ablon MD, FAAD, of Ablon Skin Institute and Research Center in Manhattan Beach, California, investigated the safety and efficacy of a nutraceutical supplement designed to promote hair growth in women in various stages of menopause. Hair loss and thinning that increase with advancing age are most common among postmenopausal women. Overall, 50% of perimenopausal, menopausal, and postmenopausal women over the age of 50 experience androgenetic hair loss. The study found that after 12 months, subjects taking the active nutraceutical supplement had improvements in hair growth, quality, and shedding. The subjects also reported improvements in their quality of life and menopausal symptoms throughout the study.

When the placebo group was transitioned to the nutraceutical supplement, the subjects experienced significant increases in their hair counts and quality, and a decrease in overall shedding. The positive results of this clinical study show that the continued use of a nutraceutical can provide substantial improvements in hair growth and quality of life among perimenopausal, menopausal, and postmenopausal women.

Women in various stages of menopause who experience hair thinning or loss are prone to damaging physiological impacts that lead to low self-esteem, anxiety, depression, and overall diminished quality of life1. The hormonal changes of menopause are a key factor in the decrease of hair diameter, change in diameter distribution, decreased growth rate, and increased miniaturization. Treatment options for hair loss in women are limited, with Rogaine (minoxidil; Johnson & Johnson) as the only FDA-approved drug with reported adverse events.

Those that participated in the study were healthy perimenopausal, menopausal, and postmenopausal women, 40 to 50 years old with Fitzpatrick I-IV skin types and self-perceived thinning hair. For the 12-month study, subjects were selected randomly to receive the oral nutraceutical supplement (n=40) or placebo (n=30) for the first six months. After the first 6 months, the first group continued to take the supplement while the placebo group was switched to the supplement for the final six months1.

The mean number of terminal hairs progressively increased from 68.1 at day 0 to 77.2 at day 360, resulting in a 13.4% improvement (P<0.0001) among subjects that received the active supplement for the full 12 months. The mean number of total hairs progressively increased from 78.4 at day 0 to 87.58 at day 360, representing a significant 11.7% improvement (P<0.0001)1.

The results from the clinical trial show evidence that continued use of a novel nutraceutical supplement provides a notable incremental improvement in hair growth and exerts a positive effect on the secondary symptoms of menopause and quality of life. There were no reported adverse events and overall, the supplement was well-tolerated throughout the 12 months. This study establishes Nutrafol as the only hair supplement brand to provide research for menopausal women and efficacy of a nutraceutical hair supplement over 12 months.

: Kogan and Raymond are employees of Nutraceutical Wellness, LLC, New York, NY. Ablon has nothing to disclose. The study was conducted with a grant from Nutraceutical Wellness LLC, New York, NY.

Glynis A, Kogan S, Raymond I. A long-term study of the safety and efficacy of a nutraceutical supplement for promoting hair growth in perimenopausal, menopausal, and postmenopausal women. 

JDDonline - Journal of Drugs in Dermatology

https://jddonline.com/articles/a-long-term-study-of-the-safety-and-efficacy-of-a-nutraceutical-supplement-for-promoting-hair-growth-in-perimenopausal-menopausal-and-postmenopausal-women-S1545961622P0783X/

Perimenopausal, menopausal, and postmenopausal women experienced a progressive improvement in hair growth, shedding, quality of life, and menopausal symptoms after 12 months with an active nutraceutical supplement.