Abstract
This cross-sectional study characterizes the frequency and degree of innovation of new dermatologic drugs approved by the US Food and Drug Administration (FDA) from 2012 to 2022.
Dermatologic drug development in the US has remained disproportionately low compared with other therapeutic classes due to lower revenue potential and benefit-to-risk ratios.1,2 Only 5 new drugs for diseases treated primarily by dermatologists were approved by the US Food and Drug Administration (FDA) between 1999 and 2009.1 However, over the past decade, opportunities for innovation in dermatologic drug development may have changed. This cross-sectional study characterized the frequency and degree of innovation of new dermatologic drugs approved by the FDA from 2012 to 2022.
Methods
We identified new and supplemental new dermatologic indications approved by the FDA for prescription topical and systemic drugs between January 1, 2012, and December 31, 2022, by reviewing annual FDA lists of new molecular entity approvals, Centers for Medicare & Medicaid Services CenterWatch, and peer-reviewed articles. We categorized drugs into 1 of 9 therapeutic areas and determined whether the drugs were included in WHO Model Lists of Essential Medicines and the FDA’s expedited development or regulatory review programs. Two dermatologists (B.U. and J.W.) reviewed the list of drugs. This study was exempt from institutional review board review in accordance with the Common Rule because human participants were not involved. We followed the STROBE reporting guideline.
We used established methods3,4 to estimate each drug’s degree of innovation based on 5 proxy measures: FDA innovation designation (first in class, advance in class, or addition to class), which we modified for dermatology drug approval to include first in indication5; clinical usefulness ratings by an independent French drug assessor; and benefit ratings by health technology assessment (HTA) organizations in Canada, Germany, and France (eMethods in Supplement 1). We used descriptive statistics to calculate annual dermatologic drug approvals and proportions based on degree of innovation measures. Analyses were performed using Microsoft Excel, version 365.
Results
We identified 52 new drug applications and 26 supplemental new indications approved by the FDA for dermatologic indications between 2012 and 2022, ranging from 2 new drugs and 0 new indications approved in 2012 to 8 and 7, respectively, in 2022 (Figure). Among the 52 new drugs, 11 (21%) were categorized as first in class and 13 (25%) as first in indication (Table). Benefit ratings by at least 1 of the 4 aforementioned organizations were available for 38 drugs. Among these drugs, 15 (39%) were rated as clinically useful or having high added therapeutic benefit by any organization. Among the 10 supplemental new indications with ratings by any of the 4 organizations, 3 (30%) were rated as clinically useful or having high added therapeutic benefit.
Figure. Annual Rate of New Dermatologic Drugs Approved by the US Food and Drug Administration (FDA) Between 2012 and 2022, by Measure of Innovation.
A, Measures are based on an FDA schematic. B, Ratings are from an independent French drug assessor (Prescrire International). C, Ratings are from health technology assessment organizations in Germany (Federal Joint Committee), Canada (Human Drug Advisory Panel), and France (Ministry of Health). NA indicates not applicable.
Table. Characteristics of New Drugs and Supplemental New Indications Approved by the FDA for a Dermatologic Indication, 2012-2022.
| Characteristic | No. (%) | |
|---|---|---|
| New drugs (n = 52) | Supplemental new indications (n = 26) | |
| FDA expedited or regulatory programa | ||
| Any program | 24 (46) | 14 (54) |
| Accelerated approval | 3 (6) | 3 (12) |
| Breakthrough | 12 (23) | 4 (15) |
| Fast track | 12 (23) | 1 (4) |
| Priority review | 23 (44) | 12 (46) |
| Orphan status | ||
| Yes | 15 (29) | 3 (12) |
| No | 37 (71) | 23 (88) |
| WHO essential medicine | ||
| Yes | 2 (4) | 0 |
| No | 50 (96) | 26 (100) |
| Drug type | ||
| Small molecule | 33 (63) | 17 (65) |
| Biologic | 19 (36) | 9 (35) |
| Route of administration | ||
| Topical | 12 (23) | 12 (46) |
| Systemic | 40 (77) | 14 (54) |
| Therapeutic area | ||
| Acne vulgaris | 3 (6) | 0 |
| Atopic dermatitis | 4 (8) | 2 (7) |
| Infectious | 10 (19) | 1 (4) |
| Melanoma | 9 (17) | 1 (4) |
| Nonmelanoma skin cancer | 7 (13) | 3 (12) |
| Pruritus | 3 (6) | 0 |
| Psoriasis (plaque or pustular) | 9 (17) | 3 (12) |
| Other inflammatory skin diseaseb | 0 | 8 (31) |
| Otherc | 7 (13) | 8 (31) |
| Approval year | ||
| 2012-2014 | 12 (23) | 3 (12) |
| 2015-2017 | 12 (23) | 4 (15) |
| 2018-2020 | 15 (29) | 9 (35) |
| 2021-2022 | 13 (25) | 10 (38) |
| Degree of innovation | ||
| Innovation designationd | ||
| First in class | 11 (21) | NA |
| First in indication | 13 (25) | NA |
| Advance in class | 10 (19) | NA |
| Addition to class | 18 (35) | NA |
| Clinical usefulnesse | ||
| Judgment reserved | 32 (62) | 21 (81) |
| Clinically not useful | 16 (31) | 4 (15) |
| Clinically useful | 4 (8) | 1 (4) |
| Added therapeutic benefit ratingf | ||
| Germany | ||
| Low | 18 (34) | 3 (12) |
| High | 10 (19) | 1 (4) |
| NA | 24 (46) | 22 (85) |
| Canada | ||
| Low | 14 (27) | 1 (4) |
| High | 2 (4) | 0 |
| NA | 36 (69) | 25 (96) |
| France | ||
| Low | 19 (37) | 6 (23) |
| High | 8 (15) | 2 (9) |
| NA | 25 (48) | 18 (69) |
Abbreviations: FDA, US Food and Drug Administration; NA, not available; WHO, World Health Organization.
Drugs can qualify for more than 1 program.
Includes alopecia areata, rosacea, hidradenitis suppurativa, and vitiligo.
For drugs, includes glabellar lines, submental fat, hereditary angioedema, graft-vs-host disease, erythropoietic protoporphyria, and removal of eschar-thermal burn. For supplemental new indications, includes rosacea, hidradenitis suppurativa, alopecia areata, cellulite, axillary hyperhidrosis, seborrheic keratosis, graft-vs-host disease, pemphigus vulgaris, vitiligo, and angiofibroma.
An FDA schematic was used to categorize the innovation designation of new drugs, modified for dermatologic drugs by including a first-in-indication classification. This schematic does not apply to supplemental new indication approvals.
Determined through review of ratings from an independent French drug assessor (Prescrire International). If drugs were categorized for indications as judgment reserved or were not evaluated, they were grouped as judgment reserved. If the drugs were categorized as possibly helpful, offers an advantage, a real advance, or bravo, they were grouped as clinically useful. If the drugs were categorized as nothing new or not acceptable, they were grouped as clinically not useful.
Added therapeutic benefit ratings were determined from Canada (Human Drug Advisory Panel), Germany (Federal Joint Committee), and France (Ministry of Health) for each drug’s indication. Drugs were rated as high if they presented substantial or moderate improvement and low if they presented slight or no improvement.
Discussion
Compared with prior decades, the number of new dermatologic drug approvals by the FDA increased between 2012 and 2022. Nearly half of these drugs were considered first in class or first in indication, and several were deemed clinically useful or to have high added therapeutic benefit by HTA organizations in Germany, Canada, or France.
Study limitations include use of individual indications to assess clinical usefulness and benefit ratings, and many drugs, particularly supplemental indications, lacked such ratings. Although indication-based ratings are more appropriate, they may underestimate a drug’s degree of innovation. We did not include reformulations of already marketed drugs or indications, such as a new topical formulation of an oral drug, although some may be considered clinically meaningful.
This study suggests that innovative dermatologic drug development may have increased over the past decade, offering promise for patients with skin disease. However, these findings also highlight opportunities to develop more truly innovative dermatologic agents, particularly for diseases with unmet therapeutic need. Prior studies found few markers of innovation, such as priority review or orphan designation, among topical medications approved from 2000 to 2014.2 Further development of HTAs, particularly in the US, and more active comparator trials for drugs that are not first in class may incentivize further innovation by identifying the drugs that offer the greatest value compared with existing therapies.6
eMethods. Drug Selection and Innovation
Data Sharing Statement
References
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Associated Data
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Supplementary Materials
eMethods. Drug Selection and Innovation
Data Sharing Statement
