What Really Drove Lipitor’s Success?

This month, Lipitor loses its patent exclusivity in the US.  This event has prompted a number of articles in the press and elsewhere.  An excellent piece was done earlier this week by Shannon Pettypiece on Bloomberg television.  She actually went to the former Warner-Lambert Parke-Davis (WL) labs in Ann Arbor, Michigan and interviewed Dr. David Canter, who led the clinical trials program for what proved to be the biggest selling drug of all time.

At the time Lipitor was launched, however, it wasn’t envisioned to be a $13 billion per year product.  In fact, as Dr. Canter pointed out, the former WL executives estimated that the initial annual sales projections would be about $600 – 800 million.  Given that Lipitor was being launched into a statin market already dominated by Merck (Mevacor and Zocor) and BMS (Pravacol), WL felt it needed a marketing partner who could help them compete.  Thus, they signed a co-marketing deal with Pfizer in 1997.

The Pfizer sales force has always been known to be among the best in the industry.  Furthermore, Lipitor was known to be able to lower LDL cholesterol more than the competitive agents, so the sales force had actual data to share with prescribing physicians to show that Lipitor was different from the other marketed statins.  But in the late 1990s, the significance of greater LDL lowering was unappreciated.  Many felt that an LDL cholesterol level under 120 mg/dL was good enough.  Furthermore, why would a physician who had been happily prescribing Zocor for years (and getting good results with patients) suddenly switch to the newest entry?

The answer lies in the studies that Pfizer carried out with Lipitor AFTER it had already been approved and on the market.  Pfizer invested over $800 million to show the importance of driving LDL cholesterol as low as possible.  One such study was “Treating to New Targets” (also known as TNT).  Conceptually, it was a simple study.  Ten thousand patients with stable coronary artery disease and a baseline level of 130 mg/dL of LDL (which was considered reasonable 15 years ago) were randomly assigned to get either 10 mg or 80 mg of Lipitor and followed for nearly 5 years.  At the end of the study, those on 10 mg of Lipitor had a median LDL level of 101 mg/dL and those on 80 mg had a median LDL cholesterol of 77 mg/dL.  More importantly, those on 80 mg of Lipitor had 22% fewer heart attacks and 25% fewer strokes.

This proved to be a landmark study.  For the first time, it was shown that lower LDL is better and that for people with a high risk of cardiac events, driving LDL levels down can be life-saving.  Suddenly, Lipitor’s potency advantage proved to have a major clinical benefit.  Pfizer also performed another major study known as CARDS (Collaborative Atorvastatin Diabetes Study) which for the first time showed that diabetics can reduce their risk of heart attacks and strokes by lowering their LDL levels with Lipitor.  Similarly, in the lipid lowering arm of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) lowering LDL cholesterol in patients with high blood pressure was shown to lower the risk of adverse cardiac events over hypertension therapy alone.

These studies and others helped to change medical practice.  The importance of lowering LDL cholesterol as much as possible in patients at risk of a heart attack or stroke was unquestionable.  In addition, these studies greatly expanded the patient population for those who would benefit from Lipitor therapy.  With these data in hand, it was easy for the Pfizer sales force to drive the Lipitor sales from $5 billion to almost $13 billion six years later.  But there is no doubt that the results from these studies proved to be crucial in recognizing the full potential of this important medicine.