Crestor, after setback in Lipitor trial, may take sales hit

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AstraZeneca's top-selling product, Crestor (rosuvastatin), is looking shaky after results from SATURN, a head-to-head study pitting the statin against Pfizer's soon-to-go-generic Lipitor (atorvastatin), were top-lined today, leaving the $5.7 billion drug bereft of superior efficacy boasting rights.

The SATURN trial was a gamble by AstraZeneca, which sought to give its flagship brand a sales boost while providing a buffer against cheaper copies of Lipitor, to become available once the latter goes off patent November 30. Instead, the results – which indicate that 40 mg Crestor did not outperform 80 mg Lipitor in one measure of atherosclerosis progression – could lead to a downgrade in the drug's formulary status and ding sales, analysts said.

In the study, researchers measured plaque build-up in the coronary artery of atherosclerosis patients by intravascular ultrasound. While findings “demonstrated a numerically greater reduction” of plaque in total volume by Crestor vs. Lipitor, the percentage of volume was not found to be statistically significant for the primary endpoint. Results for a secondary endpoint looked better. (Full data and analyses on SATURN will be presented at the American Heart Association Scientific Sessions on November 15, according to a company release.)

Based on the top-line SATURN results, Seamus Fernandez of Leerink Swann wrote in an investor note that he no no longer sees a reason for cardiologists to prescribe the lower 5- and 10-mg doses of Crestor, which account for roughly 60% of total Crestor prescribing.

Indeed, Crestor's $2.6 billion in US sales, as of 2010, could come under threat from insurers, although not for a few years. Long-term contracts the drugmaker has signed with managed care companies "could maintain the drug's formulary positioning until 2014," Fernandez added. (Its US patent is locked up until 2016.)

According to Sanford Bernstein analyst Tim Anderson, payers will use Crestor's failure to meet the primary endpoint in the trial to apply "negative pressure" in reimbursement decisions. While he called SATURN results "not horrible based on what little has been disclosed," in an investor note Anderson nevertheless shaved several hundred million dollars off of his Crestor earnings forecast, lowering 2015 peak revenue from $6.9 billion to $6.5 billion.

Crestor has been marketed based on results from AstraZeneca's 2007 METEOR study, which indicated a significantly slower rate of atherosclerosis progression vs. placebo. The results of METEOR spurred the pharma's aggressive “Us Against Athero” campaign, which gave Crestor an edge in positioning against Merck's rival cholesterol medication Vytorin.

More recently, JUPITER, another placebo-controlled trial, enabled AstraZeneca to open up Crestor marketing to patients without clinically evident heart disease.

But the results from SATURN, the first negative trial involving the drug, have inspired analyst comparisons to Merck/Schering-Plough's ENHANCE study, albeit to a lesser degree. That trial, which read out in 2008, pitted two lipid drugs against one another, Vytorin and simvastatin (Zocor).

Analysts expect the negative impact of SATURN on Crestor to be considerably less than ENHANCE was on Vytorin, whose US sales are down about 45% since the ENHANCE results broke in 2008, Anderson recalled. Several factors could temper the effect: the directional trend of the SATURN data, combined with AstraZeneca's long-term managed care contracts and the way it is communicating the data compared to Merck's handling of the ENHANCE results.

AZ has another factor in its favor: "Dr. Steve Nissen as friend not foe -- he is the the SATURN study PI vs. a study, company, and mechanism critic as with Vytorin," Fernandez pointed out.

Nevertheless, the results will have investors questioning the drugmaker's clinical trial strategy. Anderson wrote: “From a commercial perspective, neither [SATURN nor ENHANCE] should have ever been run in the first place because the downside seemed to outweigh the upside.”

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