Caduet

There is plenty happening in the statin space to ensure that class of drug s continued dominance on the druggist shelf--and it all bodes well for the business of pharmacy.

Indeed, the National Cholesterol Education Program last month recommended prescribing a statin regimen to any high-risk patient with low-density lipoprotein levels of more than 100 mg/dL, identifying a target of less than 70 mg/dL for those patients. Previously, LDL levels exceeding 130 mg/dL would have sounded high cholesterol alarm bells with the goal of bringing that LDL below 100 mg/dL.

Under previous guidelines, 36 million people qualified for statin therapy, while upper estimates on actual statin use were placed just north of 15 million. Under the new guidelines, several more millions of people would qualify for statin therapy.

The NCEP announced its new guidelines after reviewing five major clinical trials. "There is strong suggestive evidence that lower LDL cholesterol is better," stated Scott Gundy, the American Heart Association's representative to the NCEP. "But it has to be balanced against the cost and side effects of achieving very low levels, which often requires high doses of medication or combination therapy."

And in April, the American College of Physicians suggested that all people with diabetes should be supplementing with a low-dose statin for heart prevention. "Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients with known coronary artery disease and type 2 diabetes," the association recommended.

That adds almost 11 million diabetes patients to the number of consumers who should be on some form of statin therapy, according to a Pfizer study called the Collaborative Atorvastatin Diabetes Study. And though there is certainly some overlap between people with diabetes who should be supplementing with a statin and patients with an LDL higher than 100 mg/dL, that is definitely a strong lift in consumers who may one day be considering statin therapy.

Although patients may very well be walking into their doctor's offices to ask about their cholesterol after seeing news on these guidelines, remarked Patrick Holmes, vice president of Pfizer's cardiovascular group, "longer term, it's really going to require a more significant effort from physicians to put those guidelines into practice. That's where Pfizer and other companies play a really strong role in educating physicians about why the guidelines are lower."

And the industry is keeping pace with that growth in potential with the introduction of some new options.

Two new combination drugs containing statins got Food and Drug Administration approval in the past six months--and both are projected to be blockbusters. Pfizer's Caduet, which combines the company's Lipitor and Norvasc medicines into one pill, is expected to reach $1.1 billion in sales in the coming years--and without a great impact on Pfizer's franchise Lipitor treatment. Rather, Pfizer is marketing Caduet to the 30 million consumers who have a combination of high cholesterol and high blood pressure. "There is some overlap there," acknowledged Holmes, but it's a different take on two markets: hypertensives and lipid lowering.

The FDA approved Vytorin last month, a combination of Merck's Zocor and Schering-Plough's Zetia. Vytorin is projected to reach as high as $8 billion in sales. Merck and Schering-Plough hope to have the new drug launched by Labor Day.

As opposed to Caduet, Vytorin is expected to go head-to-head against other statins, especially those statins dispensed at higher doses, with its clinical trials showing that the two drugs taken together can lower LDL cholesterol in the range of 46 percent to 61 percent. "Vytorin will successfully compete as a first-line agent with all statins for all patients requiring cholesterol-lowering therapy," Adam Schechter, vice president for marketing and general manager of the Merck/Schering-Plough joint venture, told analysts in a conference call early last month.

The combination medicine targets the body's two sources of cholesterol through dual inhibition of both cholesterol production in the liver and absorption in the intestine. Vytorin pills will wholesale for $2.34 across all doses. "This is very competitive with existing first-line agents in the marketplace," Schechter said.

With Vytorin coming right out of the gates and increased competition from AstraZeneca's sophomore statin Crestor, Pfizer's Lipitor franchise may be facing its greatest challenge in keeping its footing as king of the pharmaceutical hill. And next year's prescription battle may be even more of a challenge.

Last month, the United Kingdom went live with a behind-the-counter version of Merck's statin Zocor, called Zocor Heart-Pro, retailing for as much as $27 for a 28-day pack. The United States may not be too far behind with its own OTC statin. Johnson & Johnson/Merck resubmitted its application to switch Mevacor Rx-to-OTC.

Odds are that statins will receive approval for OTC sale in the United States, especially because the health care economics will shift some of the initial burden for statin costs into the self-care arena. Add to that a satisfactory safety profile and a significant reduction in heart disease for future generations, and it won't take a mathematician to see that a statin switch makes fiscal sense.

Nonetheless, the switch process will not be an easy one. Statin switches were already denied by the FDA in 2000, and statin suppliers still may find the FDA a tough sell on the wisdom of taking a patient at risk of heart disease out of the doctor's office.

Because high LDL levels are not something that can be readily diagnosed by the layman--there are no symptoms--the statin is being marketed overseas against high-cholesterol risk factors.

On the sales side, there is some concern that an OTC statin will significantly cannibalize prescription statins. And that concern is certainly justified, especially when taking into consideration the last two blockbuster drugs to switch over-the-counter. Most managed care companies pushed allergy medicines Allegra and Zyrtec off of their preferred formularies when Claritin switched--in many cases making the co-pays for the prescription antihistamines more expensive than the cost of OTC Claritin. And although the cost of Claritin was certainly more expensive than other allergy remedies on the shelf, for those cash-paying customers, Claritin represented a deep discount against Allegra and Zyrtec.

"The goal is to maximize the best value in any of these therapeutic classes," said Robert Seidman, chief pharmacy officer for WellPoint Health Networks. For instance, when Claritin switched, it switched with the entire spectrum of prescription-only indications. Accordingly, Wellpoint removed all prescription antihistamines off their formulary. "Drugs such as Prilosec OTC are a little bit different because the OTC indications for the 20 mg dose are limited to frequent heartburn. There are some health plans that are adding Prilosec OTC to formulary and then requiring a treatment failure or contraindication of Prilosec OTC before a prescription PPI is covered," Seidman said.

"We're seeing the wonders of the free market, where [companies] are being very creative and coming up with solutions that are designed to protect affordability."

The fear then is that if a statin switches, third party payers would push the remaining single-ingredient statins into non-preferred formulary status and reprice the co-payments to incentivize an OTC statin trial purchase.

But while the low-dose versions of all statins might be pushed off formulary, higher-dose statins will not--consumers whose physicians have advised them to lower their LDL levels aggressively will have the same access to high-dose statins after any switch.

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