Shots: 

• G. Michael Lewitt and Philip M.Brown enlightened PharmaShots’ audience on Dermavant Sciences’ VTAMA cream a first-in-its-class topical prescription medication approved for Plaque Psoriasis 

• Michael & Philip discussed VTAMA’s study design along with its MOA, ROA, and formulation while shedding light on P-IV data 

• Philip further goes ahead to share details on VTAMA’s ongoing study to investigate its use in treating atopic dermatitis in adults and children > 2yrs. Philip also comments on the company’s preclinical candidate DMVT-506 

Saurabh: Please elaborate on the key details (MOA, ROA, formulations, etc.) of VTAMA (tapinarof) cream. What makes this cream better than any other treatment alternatives available for plaque psoriasis in the market?  

Michael: Plaque psoriasis is a chronic autoimmune disease that causes scaly and irritated patches on the skin. Until recently, there were only a limited number of topical treatments available to treat this condition long-term. Most patients start with topical steroids, which can be challenging to use due to limitations on where they can be applied and how often. However, Dermavant's VTAMA® (tapinarof) cream, 1% offers a novel, steroid-free topical treatment for adults with plaque psoriasis that is safe for long-term use — as demonstrated in clinical trials over 52 weeks — and on sensitive skin areas.  

VTAMA cream works by activating aryl hydrocarbon receptors (AhR) in the skin, which play an important role in homeostasis. When your skin's natural balance is disrupted due to plaque psoriasis, the active ingredient in VTAMA cream — tapinarof — helps restore the imbalance by activating AhR. Although the specific mechanisms by which VTAMA cream exerts its therapeutic action in plaque psoriasis is unknown, studies conducted in vitro, ex vivo, and in mice models demonstrate that it decreases inflammation, normalizes the skin barrier, and decreases oxidative stress.  

VTAMA cream is a first in its class topical prescription medication, and its FDA approval in May 2022 followed more than 25 years of minimal innovation in the topical psoriasis treatment landscape. VTAMA cream showed impressive efficacy in two identical 12-week clinical trials, achieving a 36% and 40% PGA success rate vs. 6% and 6% in the vehicle arms. In a 40-week, open-label, long-term extension study, 41% of patients achieved total skin clearance at least once while using the treatment. The long-term extension study was further powered to investigate how long patients could expect to stay clear or almost clear off the medicine after first achieving completely clear skin. The study revealed that these patients may be able to maintain their clearance for a median time of approximately four months without treatment! This is called the remittive effect, and it’s not something you would typically expect or would have historically seen from any topical treatment. As such, we believe VTAMA cream has the potential to change the treatment approach for adults living with plaque psoriasis. 

VTAMA cream is naturally identified, steroid-free, and only needs to be applied once a day. Its innovative formulation is non-greasy, cosmetically elegant, and absorbs quickly into the skin. Moreover, it does not contain any fragrance, petroleum jelly, para-aminobenzoic acid (PABA), parabens, or gluten.  

Saurabh: Please share the study design of the Phase-IV (DMVT-505-4002) study evaluating the efficacy and safety of VTAMA (tapinarof) cream, 1% for the treatment of plaque psoriasis specifically in the head and neck region in adults.  

Michael: DMVT-505-4002 (NCT05789576) was a Phase 4, open-label study that evaluated the efficacy and safety of VTAMA (tapinarof) cream, 1% for the treatment of adults with plaque psoriasis in the head and neck region. The study enrolled 31 adults with mild, moderate, and severe plaque psoriasis in the head and neck plaque region. Patients were given VTAMA cream once daily for 12 weeks with a follow-up one week after study completion. The efficacy of VTAMA cream was assessed using a Physician Global Assessment (PGA)evaluation of a target plaque psoriasis lesion in the head and neck region (tPGA). Safety and tolerability were also assessed by visit based on adverse events and local tolerability scores using the investigator-assessed Local Tolerability Scale (LTS).  In addition, a Patient Satisfaction Questionnaire (PSQ) was completed by patients which was specifically designed to assess patients’ satisfaction with VTAMA cream’s efficacy, formulation elegance, application ease, impact on daily life, and preference versus prior therapies.  

Saurabh: Discuss the key findings of the Phase-IV (DMVT-505-4002) trial along with various efficacy and safety endpoints and how these findings help reinforce the versatility of VTAMA cream, established through earlier trials.  

Michael: While up to 80% of patients with plaque psoriasis experience scalp psoriasis, it is often underdiagnosed and vastly under-treated. Despite the small surface area affected, disease in this area can result in considerable impact on quality of life and raise psychosocial challenges. It cannot be hidden with apparel and also causes profound pruritus. 

In the Phase 3 pivotal trials, up to 40% of VTAMA cream patients (n=683) PGA treatment success defined as a PGA score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline at Week 12 vs. ~6% of patients on vehicle (n=342). In this Phase 4 study, 88.5% of adult patients (n=23/26) met the primary endpoint tPGA score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline at Week 12. 

In the Phase 3 pivotal trials, up to 48% of adult patients (n=683) achieved PASI 75 (≥75% reduction in Psoriasis Area and Severity Index) vs. ~10% of patients (n=342) using vehicle. In the Phase 4 study, at Week 12, 96.2% (n=25/26) of patients achieved PASI 75 of the head and neck region with achievement for some patients observed as early as Week 1. 

Additionally, 80.8% of patients (n=21/26) achieved complete clearance of the target lesion with tapinarof cream at Week 12.  

Further, VTAMA cream was well tolerated with no new safety signals. The most common adverse reactions (incidence ≥ 5%) in subjects treated with VTAMA cream were folliculitis, contact dermatitis, headache, sinusitis, and seborrheic keratosis. 

These results – along with the positive Phase 4 intertriginous data released in October — expand the body of data for VTAMA cream and further demonstrate the treatment’s versatility to treat sensitive and hair bearing areas.  

Saurabh: Looking at the success of VTAMA cream in adult psoriatic patients in the US, is Dermavant looking for any indication of expansion or collaboration deals to take it to a larger target patient population across the globe?  

Philip: While VTAMA cream is already approved as a treatment for plaque psoriasis in adults and has an ongoing study in children with psoriasis.  Dermavant is also investigating VTAMA cream for the treatment of atopic dermatitis in adults and children as young as 2 years old. Last year, Dermavant released positive topline results from its ADORING 1 and 2 pivotal Phase 3 clinical trials. These results demonstrate that VTAMA cream, if FDA approved, has the potential to be safe and effective treatment option for long-term disease management in patients as young as 2 years old. Dermavant plans to submit its sNDA for VTAMA cream in atopic dermatitis to the FDA in Q1 2024. 

Atopic dermatitis, the most common type of eczema, is one of the most common inflammatory skin diseases, affecting approximately 26 million people in the U.S., including more than 9.6 million children.i 

Saurabh: Is Dermavant evaluating any other products for psoriasis or other related immuno-dermatology conditions in its pipeline?  

Philip: VTAMA has illustrated the utility of AhR as a druggable target which can positively impact inflammatory skin disease. Dermavant’s pipeline also includes DMVT-506, a next generation AhR agonist under development as a targeted non-steroidal therapeutic approach for a variety of immunological and inflammatory diseases which could be delivered through multiple routes of administration. 

IMPORTANT SAFETY INFORMATION 

Indication: VTAMA® (tapinarof) cream, 1% is an aryl hydrocarbon receptor agonist indicated for the topical treatment of plaque psoriasis in adults. Adverse Events: The most common adverse reactions (incidence ≥ 1%) in subjects treated with VTAMA cream were folliculitis (red raised bumps around the hair pores), nasopharyngitis (pain or swelling in the nose and throat), contact dermatitis (skin rash or irritation, including itching and redness, peeling, burning, or stinging), headache, pruritus (itching), and influenza (flu). 

You are encouraged to report negative side effects of prescription drugs to the FDA.  

Visit www.fda.gov/medwatch or call 1-800-FDA-1088. 

See full Prescribing Information and Patient Information. 

VTAMA® is the registered trademark of Dermavant Sciences, GmbH. 

Image Source: Canva 

About the Author: 

G. Michael Lewitt 

Dr. Lewitt graduated Summa Cum Laude from a six-year program at the University of Missouri, Kansas City School of Medicine, obtaining both his bachelor’s degree and medical doctorate by the age of 24. He did his residency at St. Louis University, and he served as Chief Resident his final year in training. Dr. Lewitt specializes in complex psoriasis and psoriatic arthritis. He currently practices in Chicago, Illinois where he is a partner with the Illinois Dermatology Institute. Dr. Lewitt also leads and performs medical dermatology clinical trials with DeNova Research.  He proudly sits on the National Psoriasis Foundation's Medical Board. 

Philip M. Brown 

Philip Brown brings over 25 years of clinical development experience to the Dermavant team. Prior to joining Dermavant in January 2019, Dr. Brown served as Head of Global Pharmaceutical Development at Galderma, as well as Senior Vice President of Clinical Development at Lexicon Pharmaceuticals, a publicly traded biopharmaceutical company. Dr. Brown received his MD from Texas Tech University Health Sciences Center School of Medicine, his JD from the University of Texas School of Law, and his BA from Hendrix College. 

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