CAREMARK April 2007 Volume 3, Issue Number 4 Pipeline Highlights from February 23, 2007 – March 29, 2007 and Recent Selected Healthcare News Highlights A monthly publication highlighting recent events in the pharmaceutical industry Pipeline Selected Upcoming First Generic Product Approvals/Launches1-3* zolpidem (Ambien®) Therapeutic Class Non-benzodiazepine sedative hypnotic agent Estimated Industry Sales in 2006 $2.18 Billion Anticipated Available Strengths Tablet(s); 5 mg and 10 mg cefdinir (Omnicef®) Anticipated Launch Date† April 2007 Other Available Medications in the Class Generics: Benzodiazepine sedative hypnotic agents are available generically. Brands: Ambien CR™ (zolpidem extended release; sanofi-aventis U.S. LLC), Lunesta™ (eszopiclone; Sepracor Inc.), Rozerem™ (ramelteon; Takeda Pharmaceuticals America, Inc.) and Sonata® (zaleplon; King Pharmaceuticals, Inc.) Therapeutic Class Cephalosporins, 3rd generation Estimated Industry Sales in 2006 $787 Million Anticipated Available Strengths Capsule(s); 300 mg Oral suspension; 125 mg/5mL and 250 mg/5mL terbinafine (Lamisil®) Anticipated Launch Date† May 2007 Other Available Medications in the Class Generics: None Brands: Cedax® (ceftibuten, Shionogi USA, Inc.), Suprax® (cefixime, Lupin Pharmaceuticals, Inc.) and Vantin® (cefpodoxime, Pharmacia & Upjohn Company) Comments Omnicef is the first of the oral 3rd generation cephalosporins to be available in a generic form. Therapeutic Class Antiinfective agents, topical antifungals Estimated Industry Sales in 2006 $682 Million Anticipated Available Strengths Tablet(s); 250 mg Anticipated Launch Date† July 2007 Other Available Medications Approved for Treating Onychomycosis Generics (various generic manufacturers): griseofulvin microsize and itraconazole Brands: Grifulvin V® (griseofulvin microsize, Ortho Pharmaceutical Corporation), Gris-PEG® (griseofulvin ultramicrosize, Novartis Consumer Health Inc.) and Sporanox® (itraconazole, Janssen, L.P.) Selected First Generic Product Approvals/Launches1,2*‡ amlodipine (Norvasc®) Dosage Form; Strength(s) Approval Date§ Tablet(s); 2.5 mg, 5 mg and 10 mg October 3, 2005 Launch Date† March 23, 2007 Comments The reference brand is used in the treatment of high blood pressure and coronary artery disease. Dosage Form; Strength(s) Tablet(s); 500 mg and 1,000 mg Approval Date§ March 22, 2007 This product is AB-rated. ciprofloxacin extended release (Cipro XR®) Launch Date† Comments March 22, 2007 The reference brand is used in the treatment of various infectious conditions (eg, urinary tract infections, chronic bacterial prostatitis, skin and skin structure infections) caused by susceptible organisms. This product is AB-rated. w w w. c a r e m a r k . c o m Recent Biologic License Application (BLA) Approvals1,2‡ Soliris™ (eculizimab) Dosage Form, Strength(s) Injection, intravenous; 10 mg/mL Indication(s) Treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis Approval Date Alexion Pharmaceuticals, Inc. Anticipated Launch March 16, 2007 Date† Comments April 2, 2007 Soliris is the first product approved for the treatment of PNH. Recent Product Launches1,2‡ Coreg CR™ (carvedilol) Dosage Form; Strength(s) Capsule(s), extended release; 10 mg, 20 mg, 40 mg and 80 mg Indication(s) Treatment of mild-to-severe heart failure of ischemic or cardiomyopathic origin, to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of " 40% (with or without symptomatic heart failure) and for the treatment of essential hypertension. Coreg CR can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. Approval Date October 26, 2006 Launch Date† March 22, 2007 Comments This product is administered once daily. Dosage Form, Strength(s) Tablet(s); 250 mg Indication(s) In combination with Xeloda® (capecitabine, Roche Laboratories Inc.), for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane and Herceptin® (trastuzumab, Genentech, Inc.) Approval Date March 13, 2007 Launch Date† March 19, 2007 Comments Tykerb is the first available oral kinase inhibitor. This product is administered once daily. GlaxoSmithKline Tykerb® (lapatinib) GlaxoSmithKline Tykerb is now available through the Caremark Specialty Pharmacy Network. Recent New Drug Application (NDA) Approvals1,2,4‡ Tekturna® (aliskiren) Dosage Form, Strength(s) Tablet(s); 150 mg and 300 mg Indication(s) Treatment of hypertension as monotherapy or in combination with other antihypertensive agents Novartis Pharmaceuticals Corporation Approval Date March 5, 2007 Anticipated Launch Date† March 2007 Comments Tekturna is the first in a new class of medications called renin inhibitors. Vyvanse™ (lisdexamfetamine) Dosage Form, Strength(s) Tablet(s); 30 mg, 50 mg and 70 mg Indication(s) Treatment of attention-deficit/hyperactivity disorder Approval Date February 23, 2007 New River † Pharmaceuticals Inc./ Anticipated Launch Date Shire US Inc. Comments w w w. c a r e m a r k . c o m Second Quarter 2007 Vyvanse is administered once daily and is a pro-drug of amphetamine that is therapeutically inactive until metabolized by the body. This product is classified as a Schedule II Controlled substance, with a boxed warning regarding a high potential for abuse. 2 Selected Recent Supplemental New Drug Application (sNDA) Approvals1,2‡ Lipitor® (atorvastatin) Dosage Form Tablet(s) Indication(s) Reduction in the risk of non-fatal myocardial infarction, fatal and non-fatal strokes, revascularization procedures, hospitalization for heart failure and angina in patients with clinically evident coronary heart disease Approval Date Pfizer Inc March 2, 2007 Comments This is a new indication for an already-approved product. Recent Supplemental Biologic License Application (sBLA) Approvals1,2‡ Humira® (adalimumab) Abbott Laboratories Dosage Form Injection, subcutaneous Indication(s) Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately-toseverely active Crohn’s disease who have had an inadequate response to conventional therapy; also for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab Approval Date February 27, 2006 Comments This is a new indication for an already-approved product. This product is available via Caremark Specialty Pharmacy Services. * This table highlights a subset of upcoming and recent generic approvals and/or launches † This Launch Date/Anticipated Launch Date may not reflect the date of availability for this medication. Due to circumstances beyond the control of Caremark, information related to prospective medication launch dates is subject to change without notice. This information should not be solely relied upon for decision-making purposes. ‡ Adapted from RxPipeline Services Week In Review. For more information contact: [email protected]<mailto:[email protected]> § The Approval Date is established by the FDA, but does not necessarily mean a generic product is available as of that date, or that such product is available. News Medication Safety Information regarding select medication safety issues can be found on the Caremark Web site at www.caremark.com > For Health Professionals > Drug Safety Alerts. Zelnorm® (tegaserod) U.S. Suspension of Marketing and Sales5 On March 30, 2007, the U.S. Food and Drug Administration (FDA) issued a Public Health Advisory (PHA) to alert the public that Novartis Pharmaceuticals Corporation has agreed to stop marketing Zelnorm, a medication approved for short-term treatment of women with irritable bowel syndrome with constipation and for patients younger than 65 years with chronic constipation. • The Zelnorm suspension of U.S. marketing and sales is occurring as a result of a new safety analysis of 29 clinical studies that found a higher chance of heart attack, stroke and worsening chest pain that can lead to a heart attack in patients treated with Zelnorm compared to those treated with placebo. • Physicians who prescribe Zelnorm should work with their patients and transition them to other therapies as appropriate to their symptoms and needs. • There may be patients for whom no other treatment options are available and in whom the benefits of Zelnorm treatment outweigh the chance of serious side effects. The FDA will work with Novartis to allow access to Zelnorm for those patients through a special program. This medication safety issue has been reviewed by the Caremark Drug Safety Committee. Caremark has created iScribe®, physician, client and participant communications regarding this issue. FDA Issues Permax® (pergolide) PHA6 On March 29, 2007, the FDA issued a PHA notifying the public that the companies that manufacture and distribute both the brand and generic versions of pergolide have agreed to withdraw the medication from the market due to the potential for heart valve damage. Pergolide is a dopamine agonist (DA) used with levodopa and carbidopa to manage the signs and symptoms (tremors and slowness of movement) of Parkinson’s disease (PD). • Two new studies showed that patients with PD who were treated with pergolide had an increased chance of serious damage to their heart valves when compared to patients who did not receive the drug. These two studies confirm earlier studies that also describe this problem. • Patients currently taking pergolide should contact their healthcare professional about alternate treatments and not abruptly stop taking their medication. Healthcare professionals should assess their patient’s need for DA therapy. If continued treatment with a DA is necessary, another DA should be substituted for pergolide. This medication safety issue has been reviewed by the Caremark Drug Safety Committee. Caremark has created iScribe®, physician and participant communications regarding this issue. w w w. c a r e m a r k . c o m 3 FDA Request Labeling Change for Sleep Disorder Medications7 On March 14, 2007, the FDA notified healthcare professionals of its request for manufacturers of sedative-hypnotics products – a class of medications used to induce and/or maintain sleep – to strengthen labeling to include stronger language concerning potential risks. • Risks include severe allergic reactions and complex sleep-related behaviors, which may include sleep-driving, making phone calls, and preparing and eating food (while asleep). Sleep-driving refers to driving while not fully awake after taking a sedative-hypnotic product, with no memory of the event. • Along with the labeling revisions, the FDA requested that each manufacturer send letters to healthcare providers to notify them about the new warnings, and to develop Patient Medication Guides to inform consumers about risks and advise them of precautions that can be taken. This medication safety issue has been reviewed by the Caremark Drug Safety Committee; it has been determined that no action is needed to further notify plan participants, physicians or clients at this time. FDA Issues PHA to Announce Strengthened Safety Information for Erythropoiesis Stimulating Agents (ESAs)8 On March 9, 2007, the FDA issued a PHA regarding new safety information, including revised product labeling, for the ESAs Aranesp® (darbepoetin alfa, Amgen Inc.), Epogen® (epoetin alfa, Amgen, Inc.) and Procrit® (epoetin alfa, Ortho Biotech Products, L.P.). These medications are commonly used in the treatment of anemia. • Based on results from recent studies, product labeling for the ESAs was revised to include a new boxed warning, updated warnings, and a change to the dosage and administration sections. • Information from four new studies in patients with cancer showed a higher chance of serious and life-threatening side effects and/or death with the use of ESAs; the studies involved an unapproved dosing regimen, a patient population for which ESAs are not approved, or a new unapproved ESA. • Another study of patients scheduled for orthopedic surgery showed a higher rate of deep vein thrombosis when treated with Procrit at the approved dose. • This new information is consistent with risks found in two studies in patients with chronic renal failure treated with an unapproved regimen of an ESA that were reported in November 2006. • The new boxed warning advises physicians to monitor hemoglobin levels and to adjust the ESA dose to maintain the lowest hemoglobin level needed to avoid blood transfusions. • Physicians and patients should carefully weigh the risks of ESAs against transfusion risks. • The FDA is in the process of reevaluating how to safely use this class of medications. This medication safety issue has been reviewed by the Caremark Drug Safety Committee. Caremark has created iScribe® and physician communications regarding this issue. FDA Issues Actimmune® (interferon gamma-1b) PHA9 On March 5, 2007, the FDA issued a PHA regarding the early halt of the INSPIRE clinical study of Actimmune (InterMune, Inc.) for idiopathic pulmonary fibrosis (IPF). Actimmune is not FDA-approved for treating IPF. • The study was stopped early because an interim analysis showed that patients with IPF who received Actimmune did not benefit. The analysis showed that 14.5 percent of patients treated with Actimmune died as compared to 12.7 percent with placebo. • Patients being treated with Actimmune for IPF should discuss with their physicians whether they should continue to receive Actimmune. • Actimmune is a biologic response modifier that is FDA-approved to reduce the frequency and severity of infections in patients with chronic granulomatous disease and to delay progression of severe, malignant osteopetrosis. References: 1. 2. 3. 4. 5. 6. 7. 8. 9. Caremark. RxPipeline Insider. Available at: www.rxpipelineinsider.com. Accessed March 2, 9, 16, 23, and 30, 2007. Drugs@FDA. Rockville, MD: Food and Drug Administration, Center for Drug Evaluation and Research. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/. Accessed March 28, 2007. Efacts. Facts & Comparisons Web site. Available with subscription at: http://online.factsandcomparisons.com/. Accessed March 28, 2007. ADIS R&D Insight. AdisInsight Web site. Available with subscription at: http://bi.adisinsight.com/login/login.aspx. Accessed March 28, 2007. FDA Public Health Advisory. Tegaserod maleate (marketed as Zelnorm). Food and Drug Administration Web site. Available at: http://www.fda.gov/cder/drug/advisory/tegaserod.htm. Accessed March 30, 2007. FDA Public Health Advisory. Pergolide (marketed as Permax). Food and Drug Administration Web site. Available at: http://www.fda.gov/cder/drug/advisory/pergolide.htm. Accessed March 30, 2007. FDA News. FDA requests label change for all sleep disorder drug products. Food and Drug Administration Web site. Available at: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01587.html. Accessed March 14, 2007. FDA News. FDA strengthens safety information for erythropoiesis-stimulating agents (ESAs). Food and Drug Administration Web site. Available at: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01582.html. Accessed March 12, 2007. FDA Public Health Advisory. Interferon gamma-1b (marketed as Actimmune). Food and Drug Administration Web site. Available at: http://www.fda.gov/cder/drug/advisory/interferon_gamma_1b.htm. Accessed March 12, 2007. © Copyright 2007 Caremark. All rights reserved. Any names and trademarks listed herein are the property of their respective manufacturers. Please note: This document provides a brief overview of various subjects. This letter is provided as reference material and is based in part on information derived from third parties. Caremark does not assume liability or responsibility for the accuracy or completeness of any third-party material footnoted in this letter. Caremark does not operate the Web sites listed here, nor is it responsible for the availability or reliability of their content. These listings do not imply or constitute an endorsement, sponsorship or recommendation by Caremark. w w w. c a r e m a r k . c o m 4