Experts Foresee Major Role For Generic Crestor

— Finally there’s a challenger to the long reign of Lipitor

The FDA approval on Friday of the first generic version of Crestor (rosuvastatin calcium) marks the end of an era and the beginning of a major shift in cardiovascular medicine. Over time, as the price of the drug drops with generic competition, it seems likely that the dominant statin in the market for two decades, atorvastatin, will cede a significant portion of its share to rosuvastatin.

The approval also indicates a likely shift in the statin debate away from the economic and business issues and toward the more purely medical issues, though it is unlikely that criticism of statins will dissolve anytime soon.

After its approval in 1996 Lipitor (atorvastatin) became not only the overwhelmingly preferred statin but the best-selling drug in history, achieving more than $125 billion in sales in less than 15 years for its manufacturer, Pfizer. When Crestor was approved in 2003 it was widely perceived to be at least as potent, if not more potent, than atorvastatin, in its cholesterol-lowering efficacy. Although it never achieved Lipitor’s level of success, by any other measure Crestor was a blockbuster for AstraZeneca, reaching over $6 billion in sales in the past year in the US. But it always labored in the shadow of Lipitor, and after the 2011 patent expiration of atorvastatin the vast majority of statin prescriptions were written for atorvastatin.

The availability of generic rosuvastatin will not have an immediate dramatic impact on the statin market. Watson has a 67 day period of exclusivity, and it may take a year or more for generic competition to lower the price to the pennies-a-day level of atorvastatin and other statins.

I asked several cholesterol experts to speculate on how generic rosuvastatin will play out in the marketplace. They all agreed that there was an important role for the drug, but that it would not immediately supplant atorvastatin. They pointed to several advantages enjoyed by rosuvastatin, including the drug’s potency— it was often referred to as the “gorilla statin” in its early days— and the possibility that it may be less likely to lead to muscle problems. Here are their comments:

Donald Lloyd-Jones (Northwestern University):This is a very exciting development certainly. Milligram for milligram, rosuvastatin is the most potent statin that is on the market. It does not have the duration of safety track record that atorva does, so I am not sure it would supplant atorva for many patients, but it is good to have another option for generic potent (high-intensity) statins. Competition is good!

We will often try it in people who appear to have side effects on atorva, because atorva is lipophilic (fat soluble) whereas rosuva is hydrophilic (water soluble), and this simple switch can make a statin much more tolerable for some patients. It is also fair to say that rosuva has fewer potential drug-drug interactions than atorva, which may be an important consideration for some patients.

James Stein (University of Wisconsin): It’s a very exciting development that I welcome eagerly, since rosuvastatin is an important part of my treatment arsenal. Rosuvastatin is the most potent statin on the market for reduction of total cholesterol, LDL cholesterol, and triglycerides – and it raises HDL-C (for what that is worth). It is not cleared by CYP P450 3A4, is hydrophilic, and has a long half-life characteristics that make it a favorable choice for many patients at risk for statin-associated muscle problems. It will take market from generic atorvastatin, but atorvastatin is an excellent statin too. The decrease in atorvastatin prescribing due to rosuvastatin’s generic status will be gradual and will not come close to the decrease in simvastatin prescribing we saw when atorvastatin came on the market.

Michael Blaha (Johns Hopkins): Rosuvastatin going generic is a boon for patients. The price will fall within a year, giving us a second high potency generic statin to choose from. I wouldn’t say that rosuvastatin will be the preferred statin – there are still no good randomized trials comparing atorvastatin to rosuvastatin. I would say that a high potency generic statin should be the for choice however for nearly all patients.

Roger Blumenthal (Johns Hopkins): It will take more than a year most likely for the price of a generic rosuva to approach that of generic atorvastatin. Rosuva is broken down in the liver by a different cytochrome p450 pathway than atorvastatin is and may have fewer drug interactions with common medications than atorvastatin.

Steve Nissen (Cleveland Clinic): Rosuvastatin is certainly the most effective statin at lowering LDL-Cholesterol, but it’s only slightly more effective than high-dose atorvastatin. In our Saturn trial, 40 mg of rosuvastatin lowered LDL-C by 6% more than 80 mg of atorvastatin. The added lipid lowering efficacy at the highest dosage may be useful in selected patients, but most patients take only 10-20 mg of atorvastatin. Accordingly, physicians are unlikely to switch to generic rosuvastatin for most patients requiring submaximal treatment.

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