0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letter |

Topical Drug Innovation From 2000 Through 2014 FREE

Jessica R. Walter, MD1; Shuai Xu, MD, MSc2,3
[+] Author Affiliations
1Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
2Department of Internal Medicine, Presence Saint Joseph Hospital, Chicago, Illinois
3Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
JAMA Dermatol. 2015;151(7):792-794. doi:10.1001/jamadermatol.2015.0231.
Text Size: A A A
Published online

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).

Place holder to copy figure label and caption
Figure.
All Priority Designations Approved for Topical Drugs From 2000 Through 2014

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.

Graphic Jump Location

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).

Table Graphic Jump LocationTable.  Breakdown of Approvals by FDA Classificationsa

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 (shuai.xu@presencehealth.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.

Nolan  BV, Levender  MM, Davis  SA, Feneran  AN, Fleischer  AB  Jr, Feldman  SR.  Trends in the use of topical over the counter products in the management of dermatologic disease in the United States. Dermatol Online J. 2012;18(2):1.
PubMed
Rickwood  S, Kleinrock  M, Nunez-Gaviria  M, Sakhrani  S, Aitken  M. The Global Use of Medicines: Outlook Through 2017. Parsippany, NJ: IMS Institute for Healthcare Informatics; 2013.
US Food and Drug Administration. Drugs@FDA: FDA approved drug products. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/. Accessed January 2, 2015.
Kinch  MS, Haynesworth  A, Kinch  SL, Hoyer  D.  An overview of FDA-approved new molecular entities: 1827-2013. Drug Discov Today. 2014;19(8):1033-1039.
PubMed   |  Link to Article
Eaglstein  WH, Corcoran  G.  New drugs and new molecular entities in dermatology. Arch Dermatol. 2011;147(5):568-572.
PubMed   |  Link to Article
Kaitin  KI, DiMasi  JA.  Pharmaceutical innovation in the 21st century: new drug approvals in the first decade, 2000-2009. Clin Pharmacol Ther. 2011;89(2):183-188.
PubMed   |  Link to Article
Xu  S, Kesselheim  AS.  Medical innovation then and now: perspectives of innovators responsible for transformative drugs. J Law Med Ethics. 2014;42(4):564-575.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
All Priority Designations Approved for Topical Drugs From 2000 Through 2014

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.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Breakdown of Approvals by FDA Classificationsa

References

Nolan  BV, Levender  MM, Davis  SA, Feneran  AN, Fleischer  AB  Jr, Feldman  SR.  Trends in the use of topical over the counter products in the management of dermatologic disease in the United States. Dermatol Online J. 2012;18(2):1.
PubMed
Rickwood  S, Kleinrock  M, Nunez-Gaviria  M, Sakhrani  S, Aitken  M. The Global Use of Medicines: Outlook Through 2017. Parsippany, NJ: IMS Institute for Healthcare Informatics; 2013.
US Food and Drug Administration. Drugs@FDA: FDA approved drug products. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/. Accessed January 2, 2015.
Kinch  MS, Haynesworth  A, Kinch  SL, Hoyer  D.  An overview of FDA-approved new molecular entities: 1827-2013. Drug Discov Today. 2014;19(8):1033-1039.
PubMed   |  Link to Article
Eaglstein  WH, Corcoran  G.  New drugs and new molecular entities in dermatology. Arch Dermatol. 2011;147(5):568-572.
PubMed   |  Link to Article
Kaitin  KI, DiMasi  JA.  Pharmaceutical innovation in the 21st century: new drug approvals in the first decade, 2000-2009. Clin Pharmacol Ther. 2011;89(2):183-188.
PubMed   |  Link to Article
Xu  S, Kesselheim  AS.  Medical innovation then and now: perspectives of innovators responsible for transformative drugs. J Law Med Ethics. 2014;42(4):564-575.
PubMed   |  Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

648 Views
0 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs