AstraZeneca announced today that its lipid-lowering agent rosuvastatin (Crestor) was not superior to atorvastatin (Lipitor, Pfizer) in reducing the progression of atherosclerosis as assessed by IVUS.
The company announced the top-line results of SATURN (Study of Coronary Atheroma by InTravascular Ultrasound: Effect of Rosuvastatin Versus AtorvastatiN), which is scheduled to be presented at the American Heart Association meeting in November. The trial compared rosuvastatin 40 mg with atorvastatin 80 mg in 1300 high risk patients.
AstraZeneca said that there was no significant difference between the two groups in the primary endpoint of the study, which was the change from baseline in percent atheroma volume (PAV) as measured by IVUS, but that the absolute numbers favored rosuvastatin. It also reported that the secondary endpoint, the change from baseline in total atheroma volume (TAV), did achieve a statistically significant difference in favor of rosuvastatin.
Analysts and journalists have noted that SATURN was designed to reach completion around the time when Pfizer would be losing its patent on Lipitor and that Astrazeneca had hoped to use the results to persuade people to pay for rosuvastatin in the face of generic atorvastatin. This task will likely be more difficult in the aftermath of SATURN.
In the Wall Street Journal Sten Stovall wondered if SATURN represented a self-inflicted wound on the part of AstraZeneca. In Forbes, Matt Herper questioned the company’s efforts to diminish the impact of the news:
The result could be worse. AstraZeneca said in its release that there was a trend toward better performance on Crestor and that using a different way of calculating the amount of plaque in the artery the difference was significant. But clinical trials live and die by their primary endpoints, to prevent findings that are just due to chance. This study failed.
Many reports have mentioned the controversy over the ENHANCE trial several years ago, which was also an atherosclerosis regression trial that missed its endpoint. But rosuvastatin has substantial evidence of benefit in placebo-controlled trials, and no concerns have been raised about the management of SATURN. By contrast, the drug tested in the ENHANCE trial, ezetimibe (Vytorin), had never been shown to produce clinical benefits, and allegations of company tampering with the analysis of the ENHANCE trial provided fuel for the flames of controversy over the trial.
Here is the press release from AstraZeneca:
AstraZeneca announces top-line results from SATURN study
Friday, 2 September 2011
AstraZeneca today announced top-line results from SATURN (Study of Coronary Atheroma by InTravascular Ultrasound: Effect of Rosuvastatin Versus AtorvastatiN). SATURN was designed to measure the impact of CRESTOR (rosuvastatin) 40 mg and atorvastatin 80 mg on the progression of atherosclerosis in high risk patients.
The results for the primary efficacy measure, which was change from baseline in percent atheroma volume (PAV) in a ≥40 mm segment of the targeted coronary artery as assessed by intravascular ultrasound (IVUS), demonstrated a numerically greater reduction in favour of CRESTOR versus atorvastatin but did not reach statistical significance.
For the secondary IVUS measure, which was change from baseline in total atheroma volume (TAV) within the targeted coronary artery, CRESTOR demonstrated a statistically significant reduction compared with atorvastatin.
Tolerability and efficacy of CRESTOR seen in SATURN were in line with previous studies and approved product labelling.
Further data and analyses will be presented by the study’s academic investigators at the American Heart Association Scientific Sessions (AHA) on Tuesday, 15 November.
NOTES TO EDITORSAbout SATURN
SATURN is a 104-week, randomized, double-blind, parallel group, multi-center Phase IIIb study of approximately 1,300 patients, investigating the effects of treatment with rosuvastatin 40 mg and atorvastatin 80 mg on atherosclerotic disease burden as measured by IVUS in patients with coronary artery disease.About PAV and TAV
Percent atheroma volume (PAV) and total atheroma volume (TAV) can be estimated as part of an intravascular ultrasound examination of a coronary artery. PAV and TAV are two different derivatives of the same measurements taken with a tiny ultrasound probe that is inserted inside the coronary artery. In effect, they take the same ultrasound data, but look at the volume of plaques, or fatty deposits, in different ways to represent what is happening in the patient’s artery.About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: http://www.astrazeneca.com