2. Agenda  Review of the significance of the FDA recommended modified labeling for over-the- counter (OTC) Nicotine Replacement Therapies (NRT)  Electronic cigarettes overview  Putting our best foot forward - NRT and the upcoming quit season  Question and Answers

3. OTC NRT Label Update

4. Background – Sequence of Events  April 1, 2013: FDA issued a consumer update stating that Nicotine Replacement Therapy Labels (gum, patch, lozenge) may change.  April 2: FDA responds to three citizen petitions relating to OTC NRTs On the same day as the CP response, FDA issued a Notice of Findings affecting the labeling of OTC NRTs  April 23, 2013: Issuance of Report to Congress under Section 918 of the FDCA: sets forth policy considerations “innovative products and treatments” to promote abstinence, reductions in consumption of tobacco, and reductions in the harm associated with continued tobacco use  Information available at : http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/u cm345928.htm

5. Citizen petitions related to OTC NRTs Submitted by:  NY Commissioner of Health (January 22, 2008)  University of Maryland School of Law (February 11, 2010)  Four not-for-profit public health organizations (August 26, 2010) including: American Cancer Society, American Lung Association, Campaign for Tobacco-Free Kids, American Legacy Foundation

6. Citizen petitions related to OTC NRTs Each of the citizen petitions requested changes to approved drug product labeling for OTC NRT products.  Certain restrictions in the labeling of OTC NRT, including those related to concomitant use and duration of use, could discourage consumers from using NRT effectively and should be removed.  OTC NRT should be approved for additional indications, e.g. for relief of symptoms during periods of temporary abstinence from smoking (unrelated to quitting). But, FDA was unable to make the requested labeling changes through the citizen petition process - changes to the labeling must be supported by submissions from product sponsors to the appropriate New Drug Applications

7. Removal of Restrictions The FDA had been conducting its own, independent review of the safety data related to NRTs  Originally approved as Rx products starting in 1980s  Starting in mid-90s, switched to OTC status, based on review of safety data available at that time Based on this, the above FDA announced that:  ‘certain statements set forth in the FDA-approved labels of over the-counter nicotine replacement therapy products, related to concomitant use with other nicotine-containing products and duration of use, can be modified.’  ‘In light of currently available evidence, these statements are no longer believed to be necessary in their current form to ensure the safe and effective use of over-the-counter nicotine replacement therapy products for their approved intended use as aids to smoking cessation.’

8. Summary of Changes

9. Implications of labeling changes: messages to convey to providers, counselors and consumers  There are no significant safety concerns associated with using more than one OTC NRT at the same time, or using an OTC NRT at the same time as another nicotine-containing product—including a cigarette. If you are using an OTC NRT while trying to quit smoking but slip up and have a cigarette, you should not stop using the NRT. You should keep using the OTC NRT and keep trying to quit.  NRT users should still pick a day to quit smoking, and begin using the OTC NRT product on their “quit” day, even if they aren't immediately able to stop smoking.  Users of NRT products should still use the product for the length of time indicated in the label—for example, 8, 10 or 12 weeks. However, if they feel they need to continue using the product for longer in order to quit, it is safe to do so in most cases. Consumers are advised to consult their health care professional if they feel the need to use an OTC NRT for longer than the time period recommended in the label.  See FDA Consumer Update at http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm345087.htm

10. As an industry leader in OTC Nicotine Replacement Therapies, GSK tasked itself with 2 initiatives: Expeditious implementation of label changes across portfolio of GSK NRT. Education of both consumers and HCP’s on the scope of the changes. Implementation - GSK

11. Updated Drug Facts Relevant text in the User’s Guide has been updated accordingly

12. New Directions for Use Flag New Directions for Use Flag to be added to the front panel of GSK NRT to highlight changes to consumers The flag will printed on all variants of NRT for a period of 6 months

13. Timing  GSK NRT with updated labeling will be commercially available in approximately 2 months time

14. Electronic cigarettes overview

15. What is an e-cigarette? An electrical, battery-powered device resembling a cigarette that contains a microelectrical circuit activated by drawing on a mouthpiece. With each puff, a small amount of nicotine-propylene glycol solution contained in replaceable cartridges is heated and vaporized, to create a visible mist without smoke or flame. Bullen C Effect of an electronic nicotine delivery device (e cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial. Tobacco Control 2010;19:98-103 battery atomizer cartridge

16. e-Cigarette History  2003: The electronic cigarette is first developed in Beijing, by Hon Lik, a 52 year old pharmacist, inventor and smoker.  2006-2007: Electronic cigarettes introduced to Europe and US.  2008-2010: the FDA determined that e-cigarettes were unapproved drug/device combination products and detained and/or refused importation.  2010 - The U.S. Court of Appeals for the D.C. Circuit, in Sottera, Inc. v. Food & Drug Administration, 627 F.3d 891 (D.C. Cir. 2010), issued a decision that e-cigarettes and other products made or derived from tobacco can be regulated as “tobacco products” under The Tobacco Control Act and are not drugs/devices unless they are marketed for therapeutic purposes. subject to general controls including: registration, product listing, ingredient listing, good manufacturing practice requirements, user fees for certain products, ect http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm252360.htm

17. e-Cigarette Market  Revenue from e-cigarettes expected to double this year to over $1 billion.  e-cigarette sales predicted to pass traditional cigarette sales by 2047 (Bloomberg Industries)  Industry consolidation: In August, Altria Group Inc. (the largest cigarette maker in the U.S) started selling its MarkTen e-cigs, reports Bloomberg. Reynolds American, (Camel and Pall Mall cigarettes) launched VUSE, what they deem ‘a game-changing product in the e-cigarette category’ earlier this year. Lorillard Inc, (third-largest tobacco manufacturer in the U.S. purchased Blu eCigs for $135 MM) http://www.forbes.com/sites/natalierobehmed/2013/09/17/e-cigarette-sales-surpass-1-billion-as-big-tobacco-moves-in/

18. e-cigarettes 2 sides to the story  The unknowns: Route of nicotine delivery – buccal versus pulmonary Excipient ingredients Quality controls Long term safety and health effects Potential as a gateway for young people  In 2013, Williams et al, identified the presence of heavy metals and silicate particles in the aerosol of one brand of e-cigarettes. A total of 22 elements were identified in the aerosol, and three of these elements (lead, nickel, and chromium) appear on the FDA’s ‘‘harmful and potentially harmful chemicals’’ list. Williams M Metal and Silicate Particles Including Nanoparticles Are Present in Electronic Cigarette Cartomizer Fluid and Aerosol. PLoS ONE 8(3): e57987

19. e-cigarettes 2 sides to the story Professor John Britton, chair of the Royal College Physician Tobacco Advisory Group comment on regulation of nicotine containing products.  ‘Electronic cigarettes and other nicotine-containing devices offer massive potential to improve public health, by providing smokers with a much safer alternative to tobacco. They need to be widely available, and affordable to smokers.’  ‘However, it is also important that these products provide nicotine as safely and reliably as possible, and are marketed and sold responsibly…….this is a pragmatic yet radical approach that could spare millions of smokers from premature death.’

20. e-Cigarettes Summary  Currently regulated under Center for Tobacco Products – not indicated for smoking cessation.  Rapidly changing marketing and regulatory environment.  More research (long term safety) is required

21. Putting our best foot forward - NRT and the upcoming quit season

22. One-word recommendation Compliance

23. NRT Recommended Use  Patch: One new patch applied every 24 hours over an 8 or 10-week program (based on cigarettes per day).  Gum and Lozenge: 12-week program. 2 or 4 mg depending on Time to First Cigarette. At least 9 pieces per day for the first 6-weeks of treatment.

24. Background  Less than a third of quit attempts utilize NRT  Even when individuals choose to utilize NRT, it is typically underutilized. Usually through stopping treatment early or by using less than the recommended amount. Potential to undermine quit attempt Shiffman S Perceived safety and efficacy of nicotine replacement therapies among US smokers and ex-smokers:relationship with use and compliance. Addiction, 103, 1371–1378

25. Background Reasons for lack of compliance  Over confidence  Concerns regarding both the safety and efficacy NRT in spite of available evidence. Several studies have investigated link between safety/efficacy perceptions and use of NRT. These studies have demonstrated that a high proportion of smokers have concerns.

26. Overview Misperception Study – Ferguson et al  900 smokers were recruited and provided with an online questionnaire about their views of NRT  Misperceptions of NRT safety were common: 93% of smokers did not know that smoking while wearing the nicotine patch does not cause heart attacks. 76% of smokers did not know that nicotine gum/lozenge are not as addictive as cigarettes. 69% of smokers did not know that NRT products are not as dangerous as cigarettes. 69% of smokers think NRT can cause cancer. Ferguson SG Providing accurate safety information may increase a smoker's willingness to use nicotine replacement therapy as part of a quit. Addictive Behaviors 36 (2011) 713–716

27. Overview Misperception Study – Ferguson et al The silver lining…  Over half of the smokers with misperceptions reported that they would be more likely to use NRT to help them quit smoking if they were exposed to information correcting their concerns

28. Final thoughts http://www.cdc.gov/mmwr/PDF/wk/mm6144.pdf Percent of adults >18 years who were current smokers* by age group – National Health Interview Survey, 2005-2011. (MMWR, Vol. 61, No.44) Overall smoking prevalence has not declined from 2010- 2011 From 2005-2011 smoking prevalence in adults18-24 years declined from 24.4% to 18.9% Current rates still exceed HP2020 target of 12% US adults

29. Questions?? Thank you