The year 2000 was the peak year for approvals (n = 19). The years 2011 and 2012 had the lowest number of approvals (n = 3). When measuring approvals by 5-year periods, 2000 through 2004 and 2005 through 2009 had 44 approvals each. The period from 2010 through 2014 had 24 approvals, a decrease of 45% compared with the prior two 5-year periods. 1 through 4 indicates the quarter.
Walter JR, Xu S. Topical Drug Innovation From 2000 Through 2014. JAMA Dermatol. 2015;151(7):792-794. doi:10.1001/jamadermatol.2015.0231
Topical medications account for $2.6 billion in yearly over-the-counter spending,1 while the total dermatology prescription market exceeds $22 billion per year.2 However, the state of innovation surrounding topical medications, a class of therapeutics most used by dermatologists, remains poorly understood.
The US Food and Drug Administration’s database3 was mined for topical approvals designed for local action on skin, hair, nails, and mucosal surfaces from January 1, 2000, through December 31, 2014. Using solely publicly available data, this study is exempt from institutional review board approval at Presence Saint Joseph Hospital. Tentative approvals, supplements, and generic approvals were excluded. Transdermal, ocular, intrainhalational, and intranasal products were also excluded. Approvals were classified by the US Food and Drug Administration designation (standard, priority, and orphan) and class (analgesics, anti-infective agents, anti-inflammatories, immunomodulators and chemotherapeutics, retinoids, corticosteroids, and others). The time of approval was determined from the date of the investigational new drug application to the approval date. The primary submitting entity was also determined.
Topical approvals fell by 45%, from 44 approvals in both the 2000 through 2004 and 2005 through 2009 periods to 24 approvals from 2010 through 2014 (Figure). The year 2000 had the highest number of approvals (n = 19), including the highest number of priority designations (n = 4). In total, 5 new topical medications have been designated for priority review, with the last designation awarded in 2001 for topical mesalamine. By class, anti-infective agents were the most commonly approved, with a peak of 27 approvals from 2000 through 2004 to 10 approvals from 2010 through 2014. Topical corticosteroids were second, with 15 approvals from 2000 through 2014. The median approval time of 306 days remained consistent for the past 15 years. Topical analgesics were an outlier, requiring a median approval time of 723 days (range, 58-4112 days).
Of 112 total new approvals, 14 represented new molecular entities (NMEs), or active ingredients not marketed before in the United States (Table). Four topical NMEs were approved in both the 2000 through 2004 and 2005 through 2009 periods. From 2010 through 2014, six topical NMEs were approved. Most approvals were for dosage changes (64 approvals), new combinations (18 approvals), and new formulations (15 approvals).
The most common indications were for the treatment of acne, tinea infections, psoriasis, and atopic dermatitis. Galderma and Valeant Pharmaceuticals represented the 2 most active companies during the study period, representing 20% of all approvals. In all, there were 57 entities responsible for topical approvals, with 46 companies accounting for 2 or fewer approvals.
We chose to include all new topical approvals in addition to NMEs. Topical therapeutics are often developed after the active ingredient has been approved in oral or injectable forms. Changes in dosing, delivery mechanism (eg, ointment to gel), and combinations can represent important innovations for topical applications. Prior studies4 focusing solely on NMEs for the entire pharmaceutical industry show that approximately 20 to 30 NMEs were approved each year from 2000 through 2013. Topical NMEs are developed at a much lower rate (0.9 NMEs per year). These findings are consistent with prior studies5 illustrating the underrepresentation of all drugs developed for primarily dermatological uses.
Dermatological illnesses are not often fatal and may be considered lower priority by policymakers. Priority designations are assigned by the US Food and Drug Administration to new drugs that represent significant improvements over existing options and command more resource investment and regulatory attention. Only 5 total topical applications and 1 topical NME were given the priority review designation compared with 45% of all pharmaceutical and biological NMEs from 2000 through 2009.6 Beyond being considered lower priority, traditional metrics of blood and urine drug levels often do not apply to topical therapies. The lack of accepted surrogate end points may explain why the median approval time for topical medications is comparable with oral and intravenous therapies despite representing a lower systemic risk. Given these regulatory challenges, the low number of active companies with the necessary expertise to develop topical therapeutics likely contributes to the continued high cost and low availability of these drugs.
Prior studies on medical innovation of devices, small molecules, and biotechnology suggest a multifaceted approach to spur future development.7 Strategies most likely to succeed include continued research funding to study diseases that are likely to be responsive to topical therapeutics and increased collaboration between academic and industry professionals. In the short term, adoption of more surrogate end points reduces the regulatory burden and may encourage companies to invest more resources in this underserved area.
Accepted for Publication: January 28, 2015.
Corresponding Author: Shuai Xu, MD, MSc, Department of Internal Medicine, Presence Saint Joseph Hospital, 2900 N Lake Shore Dr, Chicago, IL 60657 (firstname.lastname@example.org).
Published Online: March 25, 2015. doi:10.1001/jamadermatol.2015.0231.
Author Contributions: Drs Xu and Walter had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Xu.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Xu.
Administrative, technical, or material support: All authors.
Study supervision: Xu.
Conflict of Interest Disclosures: None reported.