Toronto, ON - When Merck's blockbuster cholesterol-lowering agent, Zocor (simvastatin), lost patent protection last month, the move was expected to have a large impact on the statin market, affecting sales of not just Zocor but also the other major branded statins. As expected, new data show that generic competitors to simvastatin grabbed a big share of new prescriptions for cholesterol-lowering drugs, putting pressure on the biggest-selling Lipitor (atorvastatin, Pfizer).

"Generic statins have become for any patient who needs a standard amount of lipid lowering the default choice," Dr Christopher Cannon (Brigham and Women's Hospital, Boston, MA) told heartwire. "For anyone with risk factors, such as an outpatient with high cholesterol, generic statins are usually the first choice. I've written tons of prescriptions so far."

Zocor lost patent protection June 23, 2006, and immediately sales of the generic versions of simvastatin were on the upswing. In the last week of June, 49% of new statin prescriptions in the US were for the generic drugs, according to market research data published in the Wall Street Journal [1]. Although Merck has drastically cut the price of simvastatin to remain competitive, sales of Zocor fell 14% in the first week it came off patent. Generic drug maker Teva Pharmaceuticals Industries captured 32% of new prescriptions in the US in the first week, while Dr Reddy's Laboratories, a company that has an agreement with Merck for making generic simvastatin, captured 14% of new prescriptions, the Journal reports.

"Having a relatively potent statin like simvastatin available as a generic is a step forward," Dr Steven Nissen (Cleveland Clinic, OH) told heartwire. "There is no question. It means that people can be treated at less expense."

The availability of a generic drug does carry some hazards, Nissen noted. Most insurers and pharmacy-benefit managers would obviously prefer to see patients taking generic simvastatin, but Nissen does not wish to see physicians strong-armed by payers to put everybody on a generic drug. If that happens, the higher-risk patients who need a more potent agent are going to be denied effective treatment, he said.

Generic statins have become for any patient who needs a standard amount of lipid lowering the default choice.

"The only statin with demonstrated efficacy in reducing events in acute coronary syndromes is the 80-mg dose of atorvastatin, which comes from the PROVE-IT trial," said Nissen. "Most of us really feel that this is where the evidence takes us and that is what we'll prescribe. Now, somebody who is a primary-prevention patient can probably be treated with generics, at least if their LDL-cholesterol level isn't very high. But it can't be one size fits all. It's wonderful to save costs, and I'm doing my best to do that, but I also want to make sure that my patients don't have their choices taken away. So we've got to balance the importance of saving costs with the need to be flexible in treating patients in the way they should be best treated."

Cannon told heartwire that the ideal candidate for a generic statin is one who needs a moderate amount of LDL-cholesterol reduction. This would typically be a patient with risk factors and LDL-cholesterol levels of approximately 130 mg/dL to 140 mg/dL. Simvastatin 40 mg is able to reduce to LDL levels by about 35% to 40%, he said, so the generic would be able to bring LDL-cholesterol levels to the treatment goal of less than 100 mg/dL.

"ACS patients, from the PROVE-IT study, and patients with established coronary disease, based on TNT and IDEAL, would still require aggressive lipid lowering with a more-intensive regimen, where the LDL reduction needed is at least 50%," said Cannon. "The caveats are that some patients might start with a very low LDL-cholesterol level, say 100 mg/dL, and 40% off that will bring them down to 60 mg/dL, which is their goal. So you might be able to reach even the new aggressive goals of less than 70 mg/dL with simvastatin 40 mg. It depends on the individual patient."

Nissen agreed. "Patients that need moderate LDL lowering as opposed to extreme reductions typically might be good candidates for the generic drug," he said. "There are plenty of those. For many patients it's 100 mg/dL as the target, and for some higher-risk patients it's 70 mg/dL. We need to determine what their target levels should be and where they're currently at. If the patient comes in at 150 mg/dL and their target is 70 mg/dL, you're not going to get there on a generic. So you have to be willing to use a more potent agent in that patient. I still think that the majority of patients can be treated successfully with generics, and that's good news."

We've got to balance the importance of saving costs with the need to be flexible in treating patients in the way they are best treated.

Dr Roger Blumenthal (Johns Hopkins University School of Medicine, Baltimore, MD) told heartwire that he has not yet seen the increased demand for generic simvastatin, mainly because the price of the drug has yet to come down. Within six months, he expects greater generic competition that should force the price of the drug even lower.

"I think the big impact remains people who can get to goal with a 40% reduction or less," said Blumenthal. "We'll probably say that if there are no contraindications then we'll go with simvastatin or pravastatin. Patients with an LDL target of 100 [mg/dL] but who still can't there with a 40% reduction or those patients who need to get their LDL-cholesterols down to 70 [mg/dL] will need something like Lipitor, Crestor, or Vytorin."

Despite the data from the major lipid-lowering trials, atorvastatin has also taken a hit since the emergence of generic simvastatin to the market. The week simvastatin came off patent, the share of new prescriptions written for atorvastatin declined to 40% from 42% the week before, the Journal reports. In addition, the combined number of prescriptions written by primary-care physicians for generic simvastatin and Zocor surpassed those written for atorvastatin in the first week in July. Sales for atorvastatin, according to pharmaceutical analyst Richard Evans, are expected to be considerably less in 2006 than previous years, the Journal reports.

Crestor (rosuvastatin, AstraZeneca), on the other hand, the newest statin available to doctors, is gaining market share. ImpactRx, a market research firm in New Jersey, reports that more cardiologists prescribed rosuvastatin for newly diagnosed patients or those being switched to a new drug than atorvastatin in June, a notable first for the drug. AstraZeneca reported a 31% increase in second-quarter profits this week, largely based on sales of rosuvastatin, which are up 47% in the quarter [2].

The addition of generic simvastatin has also changed the way many patients approach their doctors. Nissen, Cannon, and Blumenthal told heartwire that many patients they see are asking for the generic statin. All say that patient communication remains critical.

"I have had discussions with patients who are being treated with a high-dose of a more potent statin and who might want to switch to the generic," said Nissen. "Well, I don't want their LDL-cholesterol levels to go back up because I've switched them to a generic. I tell them that. If I believe, medically and scientifically, that the evidence supports keeping them on the brand-name agent then I will do that. Many people, however, can be switched to generics and that's fine, as long as it is done thoughtfully and with the idea that, primarily, lower is better. We don't want to throw the baby out with the bath water."

As many as 25% of patients hospitalized for some type of coronary or vascular disease don't go home on a statin. That's even in a quality-assurance program. This is mind-boggling.

Cannon told heartwire that despite the recent "lower-is-better" studies, as well as the emergence of generic simvastatin, the cholesterol story is not finished yet. The ongoing IMPROVE IT-TIMI 40 is testing whether lowering LDL levels even lower than those seen in PROVE IT will reduce cardiovascular events. This trial compares simvastatin with simvastatin/ezetimibe in approximately 10 000 patients after acute coronary syndrome.

"Hopefully, the emergence of generic statins will make statins more available to patients in need of them," said Cannon. "We're even seeing some of the current data, and we're still analyzing some of the "Get with the Guidelines" data, that as many as 25% of patients hospitalized for some type of coronary or vascular disease don't go home on a statin. That's even in a quality-assurance program. This is mind-boggling. With all that we know about the benefits of statins, patients with documented disease are still not getting them. So if this is going to be an inexpensive treatment, then hopefully this will help make it available to each and every patient."