Craig W. Lindsley Pages 434 - 434 ( 1 )
Is Zetia™ a A ‘Do Nothing’ Drug? After months of delays and on the eve of meetings with congressional investigators, results from the much anticpated ENHANCE clinical trial for Vytorin™ were finally disclosed (January 15, 2008) to the dismay of pharmacuetical giants Merck and Schering- Plough, with the announcement that VytorinTM conferred no medical benefit over Zocor™ alone [1-4]. The ENHANCE trial was launched to demomstrate superior cardiovascular protection (fewer heart attacks and strokes) with Vytorin™ versus Zocor™ and enrolled 720 patients with heterozygous familiar hypercholesterolemia, a rare condition that predisposes them to abnormally high blood cholesterol. The two year study measured the amount of artery-clogging plagues in three areas and compared patients taking Vytorin ™ versus high dose Zocor™ [1-4]. Vytroin™, approved by the FDA in 2004, is a combination drug consisting of Mercks Zocor™, an HMG-CoA reductase inhibitor (statin) that inhibits cholesterol production in the liver, and Zetia™, the first cholesterol absorption inhibitor (works in digestive track). These complimentary cholesterol lowering strategies in a single pill where touted to treat the two sources of cholesterol - heredity and diet and provide superior protection from heart attack and stroke versus stain alone therapy. Zocor™ has proven to be a safe and effective statin which lowers cholesterol and decreases the risk of adverse cardiovascular events. Zetia™, was shown to lower LDL (bad cholesterol) 15-20% in a surrogate goal trial, with no clinical support that its effects on LDL confer cardioprotection - the chief concern of patients [1-4]. These data raised questions about aggressive marketing tactics, the delays to announce negative clinical data and the issue of Brand versus cheaper Generic medications with Vytorin™ [2-4]. Many physicians and clinicians voiced their displeasure and referred to Zetia™ and Vytorin™ as ‘Do Nothing’ drugs [2-4]. Moreover, both Vytroin™ and Zetia™ had achieved blockbuster status with billions in sales/year and provided additional sales for Mercks Zocor™, which is now facing billion dollar generic competition, and a major component of Schering-Ploughs annual revenue. Mercks Zocor™ is an excellent example of the impact of the loss of patent protection and generic competition. In 2005, the statins LipitorTM and ZocorTM were ranked No.1 ($7.6 billion) and No.2 ($4.5 billion) in sales, and No. 1 and No. 11 in prescriptions dispensed, respectively. After generic variants of Zocor™ entered the market mid-year 2006, Pfizers Lipitor™ remained No. 1 in terms of both sales ($ 8.6 billion) and prescriptions dispensed (74,020) while Zocor™ slid to No.7 in sales ($3.2 billion) and No. 25 in prescriptions dispensed [5-7]. With an increasing market share in each quarter of 2007, Vytorin™ was poised to recoupe much of Zocors™ lost revenues for Merck, but the ENHANCE trial may derail this rally and drive more patients to request cheaper, generic simvastatin [1-7]. However, three larger clinical trials are underway, including the 10,000 patient IMPROVE IT trial, which Merck and Schering-Plough hope will conclusively demonstrate that Vytorin™ can reduce the number of detahs and major, adverse cardiac events versus Zocor™ alone [1-4]. Unfortunately, data from these trials will not be available for ∼ three years and the moniker of ‘Do Nothing’ drug may linger until conclusive data proves otherwise. REFERENCES  For information on the ENHANCE trial see: www.merck.com, www.sherng-plough.com  For information on the ENHANCE trial in the popular media see: www.cnn.com, keyword Vytorin and www. Healthrevolution.com, search Vytorin.  Sternberg, S. ‘Drug Trials Under Pressure’ USA Today, D1, January 17, 2008.  Rubin, R. ‘Surrogtae goals can defuddle patients’ USA Today, D2, January 17, 2008.  Lamb, E. Top 200 prescription drugs of 2006. Pharmacy Times, May 2007, pp.1-4, and reference therein.  IMS Health. Press release. March 8, 2007, www.imshealth.com.  For more information on generic drug approvals and impact on sales see the US Food and Drug  Adminstration: www.fda.gov., Molecule, of, the, Month
Vanderbilt University,Vanderbilt University Medical Center Departments of Pharmacology and Chemistry Robinson Research Buliding 804 Nashville, TN 37232-6600,USA.