Monika Vinish, PhD | Deepshikha Singh, MPH, MPharm | Stephanie Munroe, PhD

Closing The Gap:How Dermatology Research Gaps Represent Untapped Markets for Pharmaceutical Companies

How Dermatology Research Gaps Represent Untapped Markets for Pharmaceutical Companies

IntroductionUntil recently, pharmaceutical manufacturers didn't devote much of their research budgets to dermatological conditions and diseases. That leaves many skin conditions and diseases, which often have few or no effective treatments, wide open to drug development.

That's changing, as pharmaceutical and biopharmaceutical companies recognize the significant unmet need in both prevalent and less-prevalent dermatological conditions and diseases. Atopic dermatitis and plaque psoriasis, two of the three most common dermatological conditions, have multiple clinical trials in Phase II, III, and Pre-Registration stages. Even lesser-known conditions, such as alopecia areata, which affects nearly seven million people in the United States and has no cure and no specific FDA-approved treatment, is getting some research attention.

Gaps in dermatological research present potentially lucrative market opportunities for pharmaceutical companies. Patients that suffer from skin conditions and diseases also benefit. Effective treatments relieve irritating, chronic, and often painful symptoms, which improves their quality of life and lifts the psychological and social burden of a visible dermatological issue.

How to Identify Gaps in Dermatology ResearchDrug developers can identify gaps in research for an indication by conducting an exhaustive search published studies, systematic reviews, and data from registered clinical trials. Compare the number of relevant studies and preclinical programs in the works to disease burden. Along the way, you'll find clues to guide your research.

Registered Clinical TrialsSearch ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform (ICTRP) to find understudied conditions and diseases. To identify potential gaps in research, review the following:

• The number of clinical trials conducted for a specific condition or disease

• Inclusion and exclusion criteria

• Reported results, terminations, and suspensions• The reasons behind any terminations or suspensions

For example, ClinicalTrials.gov lists more than 500 clinical trials related to acne vulgaris, a common, chronic skin disease that plagues more than 680 million teenagers worldwide. Acne inversa, a less common, but debilitating form of acne that causes painful lesions, has only 18 trials recruiting, enrolling or not yet recruiting. Two drug studies were terminated; one due to low recruitment. The other drug study, sponsored by AstraZeneca, was terminated because the biologic tested did not reduce pain or severity over a placebo.

Peer-reviewed Publications Like ClinialTrials.gov, a search of published results may indicate a gap in research. Using rosacea as an example, a PubMed Central search reveals more than 3,000 published rosacea studies, but only about 200 on erythematotelangiectatic rosacea, a chronic—and common—condition with limited treatment options.

Drugs That Have Received FDA ApprovalCenterWatch provides a list of FDA-approved drugs by year, company, condition, therapeutic area, and drug name. Referring to our rosacea example, of the five FDA-approved rosacea treatments, two of them target facial erythema associated with rosacea. Do they treat all of the symptoms of erythematotelangiectatic rosacea or only transient erythema? Would these patients need a treatment that targets all symptoms?

Research Gaps in Understudied ConditionsUnderstudied conditions and diseases in need of more research and treatments include forms of acne, rosacea, psoriasis, dermatitis, urticaria (hives), and wound healing, among others. Indications with high prevalence may represent the greatest potential in the marketplace.

Contact dermatitis for example, an uncomfortable rash caused by direct contact with a substance or an allergic reaction, such as a latex allergy, happens to "almost everyone" at least once according to American Academy of Dermatology Association. Yet currently there are no specific FDA-approved treatments and few clinical trials recruiting. Doctors typically recommend antihistamines or corticosteroids to calm the rash and control symptoms.

How Dermatology Research Gaps Represent Untapped Markets for Pharmaceutical Companies

Treatment becomes especially frustrating for systemic contact dermatitis, which develops upon systemic exposure to an allergen. Patch testing to pinpoint the allergen, as well as avoiding exposure to the allergen, are both painstaking processes. Improvements to both screening and treatment could bring great relief to dermatologists and patients.

Cutaneous lupus erythematosus (CLE) is a rare dermatologic autoimmune disease that affects about two-thirds of lupus patients. People with CLE develop lesions that appear on sun-exposed areas of the body. Depending on the type of CLE, current treatment includes sunscreen, avoiding sun exposure, corticosteroids or immunosuppressive drugs.

In a study conducted to understand CLE patients' disease burden and unmet needs, researchers found patients wanted "disease-modifying therapies" that mitigate signs and symptoms of both acute and chronic conditions. They also suggested a "starter kit" about coping with CLE. Many expressed social anxiety, depression, insomnia, and negative body image.1

Research gaps in well-studied conditionsEven well-studied conditions and diseases may need new treatment options. Existing drugs may only treat certain symptoms, or they may not bring lasting results.

The National Psoriasis Foundation estimates psoriasis affects more than eight million Americans. Treatment includes biologics, systemic drugs, light therapy, topical treatments and light therapy. Yet, studies show many patients remain dissatisfied with treatments.

Researchers out of hospitals in New York, Paris, London, and other locales led a large multinational study to better understand the unmet needs of psoriasis and psoriatic arthritis patients.

Of the 3,426 patients surveyed, they found more than 80% of patients with psoriasis covering at least 4 to 6% of the total body surface area and 59% of psoriatic arthritis patients had either received only topical treatment or no treatment at all. Of patients whom had received oral or biologic therapy, 57% and 45%, respectively, discontinued therapy.

Researchers deemed treatment options as an unmet need that warranted "additional attention and action."2

Better understanding of dermatological conditions has led to an increase in biologic drugs in development. A GBI Research report predicts an increased presence of biologics over the next few years, particularly monoclonal antibodies (mAbs) and biosimilars—primarily due to unmet need for safer and more effective treatments.

The first biologic for the major dermatological disease atopic dermatitis, Dupixent (dupilumab), was approved by the FDA in March 2017. As the drug gains traction in the marketplace, we may see more biologics in the dermatology space.

Why Do Gaps Exist?Aside from the assumption of low return on investment, pharmaceutical companies may overlook dermatological conditions when comorbidities are present. Challenges in conducting clinical trials also lead to overlooked areas of research.

ComorbiditiesWhen a dermatological condition presents with a more serious disease, the higher-level disease takes priority. For example, psoriatic arthritis, cardiovascular disease, metabolic syndrome, and inflammatory bowel disease may be associated with psoriasis.3

Patients with chronic kidney disease often present with a host of dermatological diseases, including Lindsay’s Nails, xerosis cutis, dryness of the skin, nephrogenic systemic fibrosis and acquired perforating dermatosis. Naturally, physicians and researchers want to advance kidney disease knowledge and treatment to prolong life. Meanwhile, underlying dermatological conditions, which greatly impact quality of life, get less attention.

Sidebar: Opportunities in Addressing ComorbiditiesIf researchers address a secondary condition, such as skin disease, would they uncover clues to help discover new treatments for the clinically dominant illness?

How Dermatology Research Gaps Represent Untapped Markets for Pharmaceutical Companies

A study published in January 2019 by biotech startup Cortexyme Inc. suggests it's a possibility. The study found Porphyromonas gingivalis, the bacteria that causes gum disease, may contribute to Alzheimer's disease. The study confirmed P. gingivalis was present in the brains of subjects with Alzheimer's.4

As researchers continue to investigate common conditions with comorbidities, such as psoriasis; alopecia areata, which is linked to thyroid disease; and atopic dermatitis, which can coincide with lymphoma or pancreatic cancer, they could discover links to help better treat or cure clinically dominant diseases.

Research LimitationsFailure to recruit a significant number of patients for clinical trials, as well as limitations in preliminary research, makes it a challenge to study a drug's effect on human skin. Chronic nonhealing wounds, which impact nearly 8.2 million Medicare beneficiaries and account for more than $28 billion in annual Medicare spending, is one area where limitations have slowed research.

To effectively address the complex nature of chronic nonhealing wounds, researchers need to study the condition in the lab. However, outcomes produced in the lab don't always apply to humans.

Despite progress in translational research concerning wound healing, animal models don't fully predict clinical outcomes in humans. Mice and human skin simply heal differently. Wounds close by granulation tissue in humans and mainly by contraction in mice. Differences in stem cells also make it difficult to apply results obtained in mouse models to human populations.

By studying DNA and RNA, researchers have been able to investigate wound healing by using small tissue samples from humans. Skin organoids, which are 3D cell culture models that mimick the organ the cells originated from, show potential use in personalized approaches to treat psoriasis and other skin disorders.

Challenges in Closing the GapsWhile a few skin conditions and diseases are life-threatening, most are not fatal. They do, however, seriously impact patients' quality of life.

Anxiety, depression, time missed from work, stressed family relationships and friendships, and isolation are just a few ways skin conditions affect patients' well being. Clinical trial sponsors and physicians may not immediately recognize the importance of researching a quality of life issue. To the researcher, quality of life may seem less significant than a life-threatening disease. The patient, however, may see things differently.

Similarly pharmaceutical companies may hesitate to invest in a dermatological treatment. With the FDA raising the bar on safety and efficacy, in addition to a demand for quality of life impact, the cost and time involved may not equate to a reasonable return on investment when the drug enters the market.

ConclusionAs more pharmaceutical manufacturers move toward closing gaps in dermatology research, they may face roadblocks when initiating and managing clinical trials. Partnering with a CRO can help lessen the challenges that come when recruiting patients with less-prevalent conditions. By overseeing all aspects of the clinical development pathway, a CRO helps ensure clinical trial success for pharmaceutical and biopharmaceutical companies.

Biorasi has more than 15 years of experience managing dermatology studies, including many rare and complex indications. Contact us today to learn more about our project management-centered approach to dermatology clinical trials.

How Dermatology Research Gaps Represent Untapped Markets for Pharmaceutical Companies

1. Ogunsanya, M.E. et al. Understanding the disease burden and unmet needs among patients with cutaneous lupus erythematosus: A qualitative study. International Journal of Women's Dermatology, Vol. 4. Issue 3. September 2018.

2. Lebwohl, M.G., et al. Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol. 2014 May;70(5):871-81.e1-30. doi: 10.1016/j.jaad.2013.12.018. Epub 2014 Feb 24.

3. Elmets, Craig A. et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. Journal of the American Academy of Dermatology.

4. Dominy, S. et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science Advances, 23 Jan 2019: Vol. 5, no. 1, eaau3333 DOI: 10.1126/sciadv.aau3333

Resources

About the Authors

Dr. Vinish received her doctorate in neuroscience from the Postgraduate Institute of Medical Education and Research in Chandigarh, India and conducted postdoctoral research at the University of Maryland in Baltimore and at the University of Texas Medical Branch in Galveston. While in Texas, she designed and conducted clinical research investigating the role of dendritic cells in modulating burn wound healing.

Monika Vinish, PhD | Clinical Operations

Ms. Singh completed her Master Degree on Pharmacy and then continued on to earn her master’s in public health from the University of Miami Miller School of Medicine. She has a mixture of both preclinical and clinical research experience, crossing disciplines of oncology, global health policy, and pharmacovigilance. She has been with Biorasi for some time, contributing to the success of clinical trials by working closely with the Operations Team.

Deepshikha Singh, MPH, MPharm | Clinical Operations

Dr. Munroe is responsible for creating optimized solutions for dermatology-related projects within Biorasi's program development department, working closely with other branches to tailor each upcoming study. She completed her Bachelor's in Science at Florida Atlantic University and her PhD in Marine Biotechnology at Wageningen University & Research Center in the Netherlands, where she investigated marine natural products.

Stephanie Munroe, PhD | Medical & Scientific Affairs, Medical Writing

19495 Biscayne Blvd. Suite 900 | Miami, Florida 33180786.388.0700 | www.biorasi.com

Biorasi, founded in 2002, has received the coveted CRO Leadership Award from Life Science Leader magazine and has placed on the Inc. 500 list of America’s fastest growing companies. Biorasi has collaborated with sponsors to enable FDA, EMA, and multi-venue approvals for numerous small molecules and biologics. Biorasi, headquartered in Miami, Florida,

maintains office-based teams around the globe.