l Flipping the Switch: Disparity between the United States and Rest of World What Disparity? TABLE OF CONTENTS When it comes to regulatory approval for prescription medications that are available worldwide, the U.S. Switch Environment in the U.S. .................... 1. Food and Drug Administration (FDA) often leads the way. In fact, many smaller countries that do not have Switch Environment Outside the U.S. ........... 4. the infrastructure to support such a rigorous approval Why the Disparity in the U.S.? ...................... 9. process closely follow the decisions made by the FDA to regulate prescription pharmaceuticals in their own NSURE Initiative .......................................... 12. countries. While the FDA is regarded as a world leader Future of Switch .......................................... 13. for prescription medications, it is just the opposite for nonprescription medications. Numerous categories Future Potential Switches in the U.S. ........... 14. where products have been approved for nonprescrip- tion use outside the United States have been rejected Conclusion .................................................. 16. for nonprescription use by the FDA. Current Switch Environment in the United States Over the past five years, a fair number of switches has Hour and GlaxoSmithKline’s Flonase Allergy Relief. been introduced to the U.S. market; however, most of Johnson & Johnson is expected to be the third to enter these switches have occurred in categories where this new segment of allergy treatment in 2015 with its other drugs had already switched, and these were recently approved OTC version of AstraZeneca’s simply new brands or active ingredients entering the Rhinocort Allergy Spray inhaled nasal corticosteroid. existing category. Since 2010, there have only been Nexium OTC (Pfizer), Prevacid 24 Hour (Novartis), and two first-in-class switches: Oxytrol for Women Zegerid OTC (Bayer Group) are proton pump inhibitors (Merck) for the treatment of overactive bladder and that have joined first-in-class Prilosec OTC (Procter & nasally inhaled steroids in the existing category of Gamble) PPI, which entered the market in 2003. allergy treatment by both Sanofi’s Nasacort Allergy 24 www.klinegroup.com © 2015 Kline Figure 1: U.S. Rx-to-OTC Switch Progression 1970s FDA establishes OTC REVIEW/MONOGRAPH system Rx-to-OTC switch of hydrocortisone approved for use in OTC first aid and anti-itch meds 1980s 1980-1982 recession sharp spike in PL OTC sales Ibuprofen switch approved (1984) Nuprin, Advil, Motrin Many allergy, cough and cold ingredients approved for switch bringing brands like Nyquil, Benadryl, Triaminic, and Actifed to market Loperamide switch approved (Imodium) HDTK takes off with launch of new technologies 1990s 1990-1992 recession PL penetration increases across all categories Robust switch activity:N aproxen sodium (Aleve) H2 antagonists (Tagamet HB, Pepcid AC, Zantac 75, and Axid AR), Antifun- gals (Lotrimin AF, Lamisil AT); Yeast infection (Monistat, Gyne-Lotrimin, Vagistat, Femstat), children’s Ibuprofen (Children’s Advil and Motrin), smoking cessation new category (Nicorette, Nicoderm CQ, Nicotrol, Habitrol), eye care (Naphcon-A, Vasocon-A, Opcon-A, Visine-A) Hair regrowth new category (Rogaine) 2000s Fewer switches create huge brands Low and non-sedating antihistamines (Claritin, Zyrtec) PPIs (Prilosec OTC and Prevacid 24 Hour) Hyperosmotics (Miralax) Alli creates medicated weight loss market Plan B creates OTC emergency contraceptive market 2008 - great recession begins consumers highly cost-conscious, penetration of PL continues Today Widespread recalls impact market 2010-2013 J&J and Novartis plants shut down Fexofenadine (Allegra) switch approved FDA issues NSURE Initiative INS approvals (Nasacort, Flonase, Rhinocort) OAB approval (Oxytrol for Women) NSURE 2 l 2 Figure 2: U.S. Rx-to-OTC Switches, 2005-2015 Miralax Prevacid Oxytrol 24HR Zaditor for Claritin Women Plan B Eye Drops Rhinocort Nasacort Zyrtec Allergy Allergy Spray Alaway Eye Drops Allegra 24 HR Year of Approval 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Zantac Alli Nexium 150 Zegerid 24 HR OTC Zyrtec Flonase Allergy Relief Over the past decade, 17 Rx-to-OTC switch brands the overwhelming clinical experience along with the have been approved by the FDA and launched to the compelling data from the label comprehension and OTC market. 1 Over the same period of time, four self-selection studies Merck presented, an FDA Advi- switches failed attempts to switch statins for lowering sory Committee voted 11-4 against OTC approval. In cholesterol. Bristol-Myers Squibb partnered with the discussion following the vote, the members of the Bayer Consumer Care for an attempted switch of committee expressed that they wanted to see more Pravachol (pravastatin) and was denied. Merck information on the following key issues: attempted to switch Mevacor (lovastatin) three times and was also denied each time. In the case of lovasta- tin, the switch paradigm was for patients at moderate Is there a need for another OTC product for the cardiovascular risk to receive the OTC product. In the treatment of allergic rhinitis? end, FDA Advisory Committee members were skepti- cal that consumers could figure out whether they fell If available OTC, would asthmatics purchase it to into the moderate risk category, if they could assess self-treat their asthma, thus putting them at risk the efficacy of, follow the results of the medication, by taking them away from physician care? and if they could determine if they reached treatment goals. Even though labeled for age 18 and over, would adolescents age 15-17 be treated with it and Most recently (May 2014), Merck attempted to switch placed at risk for neuropsychological events? the blockbuster allergy/asthma drug Singulair and was voted down by an FDA Advisory Committee. Despite 3 l Based on recent switches, the FDA seems to be follow- er, the FDA is less inclined to approve products for ing a more conservative path in approving traditional preventing chronic conditions like asthma or heart types of OTC products used for acute, self-limiting, disease that can be more life-threatening in nature. non-life threatening conditions with readily recogniz- able symptoms that consumers can identify. Howev- Current Switch Environment Outside the United States In contrast to the FDA, regulatory agencies outside the more proactive about switch than the United States. United States have been much more aggressive in Triptans for the treatment of migraine have switched approving switches for conditions outside the typical in numerous countries including the United Kingdom, OTC paradigm. The United Kingdom in particular takes Germany, Sweden, and New Zealand. Sildenafil, the pride in being at the forefront of switching. U.K. Phar- active ingredient in Viagra was approved in October macy Minister Earl Howe has continually stressed that 2014 as a special behind-the-counter product in New increasing patient choice by making more medicines Zealand that can be sold without a prescription by available without a prescription is a priority for the pharmacists who have had special training. The phar- British government. When speaking at the Proprietary macist administers a screening tool that allows only Association of Great Britain conference in London on men ages 35-70 without heart disease to purchase the July 5, 2012, he stated, “The United Kingdom leads the product. The switch initiative was not led by Pfizer, world in the range of products available without a but rather Douglas Pharmaceuticals, which is the com- prescription—but more can always be done.” 3 pany that markets this drug in New Zealand under the brand name Silvasta. Therefore, the trade name is Over the past decade, 17 Rx-to-OTC switch brands the overwhelming clinical experience along with the The push for greater access to medicines in the United Silvasta and not Viagra and the switch sponsor in New have been approved by the FDA and launched to the compelling data from the label comprehension and Kingdom started in 2000 when the National Health Zealand is Douglas Pharmaceuticals. OTC market. Over the same period of time, four self-selection studies Merck presented, an FDA Advi- Service (NHS) outlined its aim to make more medi- switches failed attempts to switch statins for lowering sory Committee voted 11-4 against OTC approval. In cines available without prescription in order to widen Below is a list of potential switches being considered cholesterol. Bristol-Myers Squibb partnered with the discussion following the vote, the members of the access to medicines and patient choice. The NHS is the in the United Kingdom to switch from prescription-on- Bayer Consumer Care for an attempted switch of committee expressed that they wanted to see more publicly funded healthcare system for England. It is ly medications (POM) to pharmacy sales (P) according Pravachol (pravastatin) and was denied. Merck information on the following key issues: the largest and the oldest single-payer healthcare to the RPSGB. The list of potential candidates for POM attempted to switch Mevacor (lovastatin) three times system in the world. In 2000, the NHS tasked the Royal medicines to P switches groups drugs together in ther- and was also denied each time. In the case of lovasta- Pharmaceutical Society of Great Britain (RPSGB) to apeutic categories, based on chapters in the British tin, the switch paradigm was for patients at moderate take the lead in identifying potential therapeutic cate- National Formulary (BNF). Some examples of cardiovascular risk to receive the OTC product. In the gories suitable for reclassification. At the same time, proposed changes are found on the following page. end, FDA Advisory Committee members were skepti- the Pharmaceutical Industry Competitiveness Task cal that consumers could figure out whether they fell Force (PICTF) agreed the process for reclassifying into the moderate risk category, if they could assess prescription-only medicines should be streamlined. the efficacy of, follow the results of the medication, The new process was intended to make the whole and if they could determine if they reached treatment process quicker and easier for pharmaceutical compa- 4 goals.