Assessing the chiral switch: approval and use of single-enantiomer drugs, 2001 to 2011.
OBJECTIVE
A "chiral switch" occurs in the pharmaceutical market when a drug made up of 2 enantiomer forms is replaced with a purified single-enantiomer version, often in the context of a patent expiration. We studied the prevalence of chiral switching in the United States over the past decade, including trends in use of, and expenditures on, these products in Medicaid.


METHODS
Retrospective analysis.


METHODS
We used US Adopted Names prefixes (lev/levo/ar/es/dex/dextro) to identify all single-enantiomer drugs approved from 2001 to 2011. From publicly available US Food and Drug Administration (FDA) approval documents, we extracted the characteristics of the pivotal premarket trials for the single enantiomers. Specifically, we evaluated whether the single enantiomer was directly compared with the precursor racemic drug and whether there was evidence of superior efficacy. We used quarterly drug expenditure data from each state Medicaid program to chart trends in use of, and spending on, the single-enantiomer products and their racemic precursors during the study period.


RESULTS
From 2001 to 2011, the FDA approved 9 single-enantiomer products: dexlansoprazole, levoleucovorin, levocetirizine, armodafinil, arformoterol, eszopiclone, escitalopram, dexmethylphenidate, and esomeprazole. Of those 9 drugs, 3 had at least 1 pre-approval randomized trial that included the racemic precursor as a direct comparator, but there was no evidence of superiority of the single enantiomer over the racemic at comparable doses. Between 2001 and 2011, US Medicaid programs spent approximately $6.3 billion on these 9 single-enantiomer drugs.


CONCLUSIONS
Recently approved single-enantiomer drugs showed no evidence of superior efficacy over the older racemic precursors in the pivotal trials leading to their approval, and in a majority of cases, they were not directly compared.
Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, 7180 Highland Dr, Pittsburgh, PA 15206. E-mail: walid.gellad@va.gov.>
Walid F
WF
Gellad
Phillip
P
Choi
Margaret
M
Mizah
Chester B
CB
Good
Aaron S
AS
Kesselheim
D000931:Antidotes / Q000737:chemistry / Q000191:economics; D053961:Azabicyclo Compounds / Q000737:chemistry / Q000191:economics; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000191:economics; D001993:Bronchodilator Agents / Q000737:chemistry / Q000191:economics; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000191:economics; D017332:Cetirizine / Q000737:chemistry / Q000191:economics; D064748:Dexlansoprazole / Q000737:chemistry / Q000191:economics; D064699:Dexmethylphenidate Hydrochloride / Q000737:chemistry / Q000191:economics; D017277:Drug Approval; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D016568:Drugs, Generic / Q000191:economics; D064098:Esomeprazole / Q000737:chemistry / Q000191:economics; D000069582:Eszopiclone; D004983:Ethanolamines / Q000737:chemistry / Q000191:economics; D000068759:Formoterol Fumarate; D039563:Histamine H1 Antagonists, Non-Sedating / Q000737:chemistry / Q000191:economics; D006801:Humans; D006993:Hypnotics and Sedatives / Q000737:chemistry / Q000191:economics; D058766:Levoleucovorin / Q000737:chemistry / Q000191:economics; D008484:Medicaid / Q000191:economics*; D000077408:Modafinil; D010330:Patents as Topic; D010879:Piperazines / Q000737:chemistry / Q000191:economics; D054328:Proton Pump Inhibitors / Q000737:chemistry / Q000191:economics; D012189:Retrospective Studies; D013237:Stereoisomerism; D014481:United States; D014486:United States Food and Drug Administration; D064690:Wakefulness-Promoting Agents / Q000737:chemistry / Q000191:economics
D000931:Antidotes; D053961:Azabicyclo Compounds; D001559:Benzhydryl Compounds; D001993:Bronchodilator Agents; D000697:Central Nervous System Stimulants; D016568:Drugs, Generic; D004983:Ethanolamines; D039563:Histamine H1 Antagonists, Non-Sedating; D006993:Hypnotics and Sedatives; D010879:Piperazines; D054328:Proton Pump Inhibitors; D064690:Wakefulness-Promoting Agents; D064699:Dexmethylphenidate Hydrochloride; C472067:levocetirizine; D058766:Levoleucovorin; D064098:Esomeprazole; D000077408:Modafinil; D064748:Dexlansoprazole; D000069582:Eszopiclone; D000068759:Formoterol Fumarate; D017332:Cetirizine