Fool Me Twice? The Reemergence of Rofecoxib and the Orphan Drug Act
Authors: Theodore T. Lee, Daniel H. Solomon, Aaron S. Kesselheim
Journal: Annals of Internal Medicine (2019)

Ideas and Opinions15 October 2019Fool Me Twice? The Reemergence of Rofecoxib and the Orphan Drug ActTheodore T. Lee, JD, Daniel H. Solomon, MD, MPH, and Aaron S. Kesselheim, MD, JD, MPHTheodore T. Lee, JDYale Law School, Yale University, New Haven, Connecticut (T.T.L.)Search for more papers by this author, Daniel H. Solomon, MD, MPHBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (D.H.S.)Search for more papers by this author, and Aaron S. Kesselheim, MD, JD, MPHProgram On Regulation, Therapeutics, And Law (PORTAL), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.S.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-1218 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In November 2017, a small pharmaceutical manufacturer earned orphan drug designation for its drug TRM-201 (rofecoxib) as a pain treatment of hemophilic arthropathy (HA) (1), which causes chronic pain and functional limitation in patients with severe and moderate hemophilia A and B. Hemophilia affects approximately 20 000 persons in the United States, and although treatment of hemophilia can reduce HA incidence, HA remains a source of illness. It is commonly treated symptomatically with opioids paired with occasional joint drainage and corticosteroid injections. Because of concerns about opioid dependence and the lack of HA medications that are approved by the U.S. Food ...References1. FDA grants orphan drug designation for TRM-201 (rofecoxib) for the treatment of hemophilic arthropathy. Business Wire. 21 November 2017. Accessed at www.businesswire.com/news/home/20171121005216/en/FDA-Grants-Orphan-Drug-Designation-TRM-201-rofecoxib on 15 April 2019. Google Scholar2. Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet. 2005;365:475-81. [PMID: 15705456] CrossrefMedlineGoogle Scholar3. U.S. Food and Drug Administration. Orange Book: Approved Drug Products With Therapeutic Equivalence Evaluations. 31st ed. Washington, DC: U.S. Department of Health and Human Services; 2011. Google Scholar4. Sasinowski FJ, Panico EB, Valentine JE. Quantum of effectiveness evidence in FDA's approval of orphan drugs: update, July 2010 to June 2014. Ther Innov Regul Sci. 2015;49:680-97. [PMID: 30227043] doi:10.1177/2168479015580383 CrossrefMedlineGoogle Scholar5. Kesselheim AS, Myers JA, Solomon DH, et al. The prevalence and cost of unapproved uses of top-selling orphan drugs. PLoS One. 2012;7:e31894. [PMID: 22363762] doi:10.1371/journal.pone.0031894 CrossrefMedlineGoogle Scholar6. Cisternas MG, Murphy L, Sacks JJ, et al. Alternative methods for defining osteoarthritis and the impact on estimating prevalence in a US population-based survey. Arthritis Care Res (Hoboken). 2016;68:574-80. [PMID: 26315529] doi:10.1002/acr.22721 CrossrefMedlineGoogle Scholar7. Sarpatwari A, Franklin JM, Avorn J, et al. Are risk evaluation and mitigation strategies associated with less off-label use of medications? The case of immune thrombocytopenia. Clin Pharmacol Ther. 2015;97:186-93. [PMID: 25670524] doi:10.1002/cpt.17 CrossrefMedlineGoogle Scholar8. Blanchette CM, Nunes AP, Lin ND, et al. Adherence to risk evaluation and mitigation strategies (REMS) requirements for monthly testing of liver function. Drugs Context. 2015;4. [PMID: 25709706] doi:10.7573/dic.212272 CrossrefMedlineGoogle Scholar9. Kim J, Kapczynski A. Promotion of drugs for off-label uses: the US Food and Drug Administration at a crossroads. JAMA Intern Med. 2017;177:157-8. [PMID: 27820607] doi:10.1001/jamainternmed.2016.7151 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Yale Law School, Yale University, New Haven, Connecticut (T.T.L.)Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (D.H.S.)Program On Regulation, Therapeutics, And Law (PORTAL), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.S.K.)Acknowledgment: The authors thank Dr. Ameet Sarpatwari, JD, PhD, for his comments on an earlier draft.Financial Support: Dr. Kesselheim's work is funded by the Open Society Foundations, as well as by Arnold Ventures, the Engelberg Foundation, and the Harvard-MIT Center for Regulatory Science.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-1218.Corresponding Author: Aaron S. Kesselheim, MD, JD, MPH, Division of Pharmacoepidemiology & Pharmacoeconomics, 1620 Tremont Street, Suite 3030, Boston, MA 02120; e-mail, [email protected]harvard.edu.Current Author Addresses: Mr. Lee: 1114 Avenue of the Americas, Floor 43, New York, NY 10036.Dr. Solomon: Division of Rheumatology, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115.Dr. Kesselheim: Division of Pharmacoepidemiology & Pharmacoeconomics, 1620 Tremont Street, Suite 3030, Boston, MA 02120.Author Contributions: Conception and design: T.T. Lee, D.H. Solomon, A.S. Kesselheim.Drafting of the article: T.T. Lee.Critical revision of the article for important intellectual content: T.T. Lee, D.H. Solomon, A.S. Kesselheim.Final approval of the article: T.T. Lee, D.H. Solomon, A.S. Kesselheim.Obtaining of funding: A.S. Kesselheim.This article was published at Annals.org on 1 October 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 2019Volume 171, Issue 8Page: 578-579KeywordsDrug safetyDrugsFood and Drug AdministrationMotivationOsteoarthritisPharmacoepidemiologyRapid eye movementSafetyStrokeTherapeutic drug monitoring ePublished: 1 October 2019 Issue Published: 15 October 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...