US prescriptions posted solid sales growth in 2004, although sales were dampened in top categories such as antidepressants, pain remedies, and antiulcerants by factors including drug safety issues and generic competition. Drug sales advanced by 8.3% to $235.4 billion, propelled by doubledigit growth in anticholesterol and antihypertension drugs, and by new drug entries such as Eli Lilly's depression drug Cymbalta and Vytorin, a statin and cholesterolreducer combination drug from Merck/Schering- Plough. New molecular entities earning approval increased to 31 from 21 in 2003, according to IMS Health. Growth in brand sales dropped below 10% for the first time since 1995, as generics sales growth dramatically slowed to 10%. Among the reasons for slower sales were a mild flu season and inroads by OTC heartburn and hay fever medications, IMS reported.
HMG-CoA reductase inhibitors (statins) gained a boost from a Harvard Medical School study of high-risk patients hospitalized with heart disease that was published last year. The study showed that the patients were significantly less likely to have heart attacks or require major heart surgery when they took high doses of Pfizer's Lipitor (atorvastatin calcium) to reduce low-density lipoprotein cholesterol to levels far below what most doctors have recommended. Experts said that the study will prompt a reevaluation of cholesterol level guidelines, and that the results may apply to anyone who is at risk for heart disease or has elevated cholesterol levels. Sales of Lipitor grew by 14%, as the $15.5-billion category increased by 12%. AstraZeneca's Crestor (rosuvastatin calcium), launched in late 2003, rose to #85 in the dollar rankings, while Merck/ Schering-Plough's Zetia (ezetimibe) fell out of the top 200.
In antihypertensive medications, angiotensin II receptor blockers (ARBs) grew by 24%, as angiotensin-converting enzyme inhibitors and calcium channel blockers saw declining and flat sales, respectively. ARBs were favored by clinical studies showing their value in treating diabetes patients with high blood pressure and kidney disease, and in patients with heart failure. Novartis' Diovan (valsartan) climbed to #53 from #61 last year, and Merck's Cozaar (losartan potassium) came in at #69. Although antihistamine category sales continued their slide from last year, GlaxoSmithKline's (GSK) Advair Diskus (salmeterol/fluticasone) asthma and chronic bronchitis inhaled steroid drug and Merck's Singulair (montelukast sodium) for asthma and allergy ranked among the 20 top-selling drugs, with sales growth of 26% and 25%, respectively. Sanofi-Aventis' anti?blood clotting drug Plavix (clopidogrel) posted sales growth of 33%. Drug-safety issues moved to the forefront and raised speculation that the FDA might see fit to increase regulatory scrutiny and require more testing and data before approving new drugs.
Safety concerns impacted sales in a number of drug classses in 2004. Concerns arose this year when Elan Corp and Biogen Idec suspended sales of their new multiple sclerosis (MS) drug Tysabri (natalizumab) after one patient taking the drug died from a nervous system infection and a second suspected case of infection was identified. Tysabri had been widely expected to become the leading treatment for MS worldwide. COX-2 sales continued to lose steam due to concerns about cardiovascular safety and their high costs. Merck's voluntary withdrawal of Vioxx (rofecoxib) in September and the withdrawal of Pfizer's Bextra (valdecoxib) in April at first threw sales to other COX-2s, which saw an initial 25% sales increase, said Lisa Morris, global director, IMS Longitudinal Services. However, "over time, COX-2 usage has declined to below pre-Vioxx withdrawal levels, due in part to further safety concerns about this class of drugs," Morris said. Pfizer's Celebrex (celecoxib) posted a 7% sales gain in 2004.
Antidepressant sales climbed only 1% after seeing double- digit growth in 2003, amid reports that the drugs caused suicidal behavior in children. Most of the decline is attributable to decreased prescribing to children, according to a source at a health plan company. The FDA ordered that "black box" warnings should be on the most widely prescribed drugs, and that patients should receive medication guideline material. The Piper Jaffray securities research firm reported that doctors saw 25% fewer new depressed or anxious patients in 2004 than in the previous year. Generic competition in the category also claimed sales from leaders such as GSK's Wellbutrin SR (bupropion) and Forest Laboratories' Celexa (citalopram), as Forest Labs shifted its promotional efforts to Celexa's modified version of Lexapro. Lexapro moved from #46 to #27 in US dollar sales.
Proton Pump Inhibitors
Proton pump inhibitors (PPIs) saw declining sales after double-digit growth in 2003, with increasing usage of AstraZeneca's Prilosec OTC. Generic omeprazole fell from #44 to #174. "Many insurers are not willing to cover this class of drugs at all, or they are requiring prior authorization [when brands are used]," said Jim Owens, director of clinical services and professional development at the Happy Harry's drug chain. Yet, brands' marketing, a shortage of Prilosec OTC on the market, and the limited indication for the OTC PPI have had a telling effect on some brands. Sales of AstraZeneca's Nexium and Wyeth's Protonix charged ahead with 20+% sales growth.