AstraZeneca’s GALAXY Studies And Plans For Crestor’s Ongoing Development

Company executives discuss on-going efforts to differentiate Crestor in the increasingly crowded cholesterol-lowering market.

As the world now knows, AstraZeneca has taken an important step forward in its effort to differentiate its cholesterol-lowering drug Crestor in an increasingly crowded market. The results of its study JUPITER were released last week in the New England Journal of Medicine and widely discussed at a major concurrent American Heart Association meeting. JUPITER, however, is only one part of the company's efforts to expand Crestor's label and indications (¹ (Also see "Will JUPITER Change Statin Use?" - Pink Sheet, 10 Nov, 2008.)). If the company can position Crestor more broadly than as just a lipid-management tool, it has a shot at maintaining strong growth beyond Pfizer's Lipitor patent expiration in 2011, analysts say. JUPITER is a positive development for this broad s strategy and an interesting take on how to distinguish a brand-name drug in a market filled with generics.

AstraZeneca's head of marketing James Blasetto, VP strategic development, and Lisa Nanfra, executive director commercial oper ations, recently spoke with "The Pink Sheet" DAILY abo ut the company's efforts to expand Crestor's utility in the clinic; subsequent interviews were also conducted with other company representatives. The company has an ongoing GALAXY clinical trials program, which includes JUPITER as one of 17 trials aimed at positioning Crestor as the statin with "the best effects on the atherogenic lipid profile and beneficial changes on inflammatory markers." Seven of the studies, including JUPITER, are completed, while 10 are ongoing; AstraZeneca says more are in the works. Three of the completed or near-completed studies measure outcomes, and therefore aim to confirm that Crestor is effective in reducing cardiovascular morbidity and mortality.

GALAXY results have already merited expansions in Crestor's market. Crestor U.S. sales increased 14 percent in the first nine months of 2008 to $1.2 billion, while the overall statin market has grown in the low single digits, at best.

"The Pink Sheet" DAILY: You had been expecting favorable results from JUPITER for some time, what are your marketing strategies for Crestor going forward?

Lisa Nanfra: Right now, our focus is on ensuring that we're using our current label to promote. It would be inappropriate for us to promote anything until we have an FDA approval for this data...

In November of last year we were approved with a new indication to slow the progression of atherosclerosis, so essentially our focus today is on our current label, or patients with hyperlipidemia, and really looking at how doctors define success in those patients and it is lowering LDL. Crestor, in previous studies, has been shown to be the most effective statin at lowering LDL and has a significant effect on raising HDL and slows the progression of atherosclerosis, so that's our focus.

[FDA approved Crestor to slow the progression of atherosclerosis in patients with elevated cholesterol based largely on METEOR. (Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin), one of the GALAXY trials. METEOR showed that people with early signs of the disease, elevated LDL cholesterol, and low cardiovascular risk, who took 40 mg daily of Crestor, had slower build up of arterial plaque than people on placebo (² (Also see "Crestor Atherosclerosis Indication Adds Point Of Difference, Brand Leader Says" - Pink Sheet, 9 Nov, 2007.). Unlike JUPITER, it was not an outcomes study. AstraZeneca then launched an advertising campaign for Crestor in January, highlighting this data during the height of Schering-Plough/ Merck's controversy over ENHANCE data for Vytorin (³ (Also see "AstraZeneca Revitalizes Crestor With Atherosclerosis Ad Campaign" - Pink Sheet, 31 Jan, 2008.)).}

TPSD: What happened to Crestor's market share when it received FDA approval for the atherosclerosis indication?

AstraZeneca: We are seeing increasing interest in the clinical profile of Crestor from physicians since receiving the atherosclerosis indication. As the only statin with proven efficacy to lower LDL-C, raise HDL-C, and slow the progression of atherosclerosis at any stage of the disease, Crestor share has grown since the beginning of the year. [Just prior to the JUPITER results, analysts estimated Crestor had a 9.3 percent share of the total statin market scripts volume. On a call following the study release, CEO David Brennan said Crestor sales grew 28 percent (in constant currency) last quarter and is the only statin growing this year.]

TPSD: What studies are under way now to evaluate Crestor, following JUPITER?

James Blasetto: We do have other studies ongoing in the GALAXY program right now. One, called AURORA [A study evaluating the Use of Rosuvastatin in patients requiring Ongoing Renal dialysis: an Assessment of Survival and Cardiovascular Events], is a placebo-controlled trial looking at, again, Crestor and whether or not it will have an impact on cardiovascular events in patients with [end-stage] renal failure [on chronic hemodialysis], and we also have an imaging study right now called the SATURN [Study of Coronary Atheroma by InTravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin] trial, which is also ongoing.

[AstraZeneca did not outline expected dates of completion for the ongoing studies. However, the firm is expected to submit two FDA filings next year: one based on the JUPITER results, and the other pending outcomes of AURORA. AURORA, like JUPITER, measures morbidity and mortality outcomes.

The full impact from Jupiter will not be known for years, though consensus forecasts for Crestor have risen consistently this year, driven by the atherosclerosis indication and helped by the decline in prescriptions for Vytorin, analysts say.]

TPSD: How will the JUPITER results, which show Crestor lowers C-reactive protein and LDL levels, factor into the drug's clinical use?

AstraZeneca: Atherosclerosis is a disease process that has an inflammatory component, which could be reflected through the finding of an elevated hsCRP, hsCRP is thus considered to be a marker that identifies patients at increased risk for atherosclerotic cardiovascular disease.

-Carlene Olsen ([email protected])