Kathleen Grim
Executive Director, Regulatory Compliance
Sepracor Inc. 
84 Waterford Drive
Marlborough, MA 01752-7010
 

Re:  NDA # 021476
       Lunesta® (eszopiclone) Tablets
       MACMIS # 18705

The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a 60-second direct-to-consumer (DTC) broadcast television advertisement (TV ad) entitled “Boxing Bed” (LUN317-09) for Lunesta (eszopiclone) Tablets (Lunesta) submitted by Sepracor Inc.  (Sepracor) under cover of Form FDA 2253.  The TV ad presents unsubstantiated claims, including unsubstantiated superiority claims.  Thus, the TV ad misbrands the drug in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 352(n), and FDA implementing regulations.  21 CFR 202.1(e)(5)(i); (e)(6)(i) & (ii). 

Background

The INDICATIONS AND USAGE section of the approved product labeling (PI) for Lunesta states (in pertinent part):

LUNESTA is indicated for the treatment of insomnia.  In controlled outpatient and sleep laboratory studies, LUNESTA administered at bedtime decreased sleep latency and improved sleep maintenance. 

Lunesta is associated with serious risks as reflected in the WARNINGS section of its PI, including the need to evaluate for co-morbid diagnoses, as the failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness.  Additional Warnings include abnormal thinking and behavior (e.g., aggressiveness, bizarre behavior, agitation, hallucinations, depersonalization), complex behaviors (e.g., “sleep-driving,” preparing and eating food, making phone calls, and/or having sex, with amnesia for the event), worsening of depression in primarily depressed patients including suicidal thoughts and actions (including completed suicides), severe anaphylactic and anaphylactoid reactions and CNS-depressant effects.  Lunesta has a rapid onset of action and should only be ingested immediately prior to going to bed or after the patient has gone to bed and has experienced difficulty falling asleep, and patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination.  Lunesta should not be taken with alcohol.  Furthermore, Lunesta is a Schedule IV controlled substance under the Controlled Substances Act because it can be abused or lead to dependence.  The most common adverse reactions associated with Lunesta include unpleasant taste in mouth, headache, dizziness and morning drowsiness. 

Unsubstantiated Superiority Claims

Promotional materials are misleading if they represent or suggest that a drug is safer or more effective than another drug, when this has not been demonstrated by substantial evidence or substantial clinical experience. 

The TV ad includes the following claims:

•  “If you've taken your sleep aid, and you're still fighting to sleep in the middle of the night, why would you go one more round using it? You don't need a rematch, but a rethink with Lunesta.  Lunesta is different.  It keys into receptors that support sleep, setting your sleep process in motion."

•  “…ask your doctor about switching to Lunesta and discover a restful Lunesta night."

These claims misleadingly imply Lunesta is clinically superior to other medications for the treatment of insomnia and that Lunesta will be an effective sleep medication in situations where treatment with other medications has failed.  FDA is not aware of substantial evidence or substantial clinical experience to support these implications.  If you do, in fact have data that supports these implications, please submit them to FDA for review. 

Unsubstantiated Claim

The TV ad includes the following claims (emphasis added):

•  “Lunesta is different.  It keys into receptors that support sleep, setting your sleep process in motion."

This claim is misleading because it implies a greater degree of certainty about the mechanism of action of Lunesta than is supported by substantial evidence or substantial clinical experience.  The Pharmacodynamics section of the PI for Lunesta states, "The precise mechanism of action of eszopiclone as a hypnotic is unknown, but its effect is believed to result from its interaction with GABA-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors.” (emphasis added) Furthermore, this claim is misleading because it implies that Lunesta’s mechanism of action is specific for and only affects the sleep-cycle when this is not the case.  Lunesta also carries many potential risks for serious adverse effects (see Background section), including the potential for abuse or dependence. 

Conclusion and Requested Action

For the reasons discussed above, the TV ad misbrands Lunesta in violation of the Act, 21 U.S.C. 352(n), and FDA implementing regulations.  21 CFR 202.1(e)(5)(i); (e)(6)(i) & (ii). 

DDMAC requests that Sepracor immediately cease the dissemination of violative promotional materials for Lunesta such as those described above.  Please submit a written response to this letter on or before June 23, 2010, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) for Lunesta that contain violations such as those described above, and explaining your plan for discontinuing use of such materials. 

Please direct your response to the undersigned at the Food and Drug Administration, Center for Drug Evaluation and Research, Division of Drug Marketing, Advertising, and Communications, 5901-B Ammendale Road, Beltsville, MD, facsimile at 301-847-8444.  In all future correspondence regarding this matter, please refer to MACMIS # 18705 in addition to the NDA number.  We remind you that only written communications are considered official. 

The violations discussed in this letter do not necessarily constitute an exhaustive list.  It is your responsibility to ensure that your promotional materials for Lunesta comply with each applicable requirement of the Act and FDA implementing regulations. 

Sincerely,

Carrie Newcomer, PharmD
Regulatory Review Officer
Division of Drug Marketing,
Advertising and Communications