Merck, Schering-Plough: More Nails in Vytorin’s Coffin

“Lowering cholesterol doesn’t mean you prevent heart attack, stroke, and death. People don’t die of cholesterol, they die of these events. We have to know whether drugs actually reduce the things we really care about, which is heart attack, stroke, and other complications of heart disease.” - Dr. Steven Nissen, Chief of Cardiology at The Cleveland Clinic to CNBC’s Mike Huckman

On Monday, shares of Merck (MRK) dropped $6.56 to $37.95, and Schering-Plough (SGP) fell $5.06 to $14.41, after a panel of cardiologists at the American College of Cardiology conference said the companies jointly marketed cholesterol drug Vytorin should only be prescribed as "a last resort."

Vytorin is a combination of Schering’s Zetia and Merck’s Zocor. (Zocor is available in generic form as simvastatin.) The two companies tout that Vytorin lowers cholesterol and triglycerides, while de-emphasizing that plaque increased in many patients taking Vytorin in the companies Enhance study. Joint venture sales for Vytorin were $5.2 billion in 2007.

Lehman (LEH) estimates scripts are down 20% between the January 14, 2008 release of the Enhance study information and Sunday’s cardiology conference.

And the hurdles to keep Vytorin financially profitable are growing. Monday, Senator Grassley, the ranking Republican of the Senate Finance Committee, released a letter citing email messages between Dr. Kastelein, a cardiologist the companies hired to be the lead investigator of the Vytorin Enhance trial. The emails show that Dr. Kastelein felt the delay in the companies presenting the study’s results were “to hide something.”

As Senator Grassley points out in his letter, the federal government has spent “hundreds of millions of dollars” for Vytorin which costs $100+ per month vs. a generic statin. (Let alone the healthcare cost if plaque-filled arteries from taking Vytorin create cardiac events!) Or, as Harlan Krumholz, the Yale cardiologist and cardiology conference panel leader told Bloomberg:

It could also be that Zetia is just an expensive placebo and its principal harm is it drains precious resources from our healthcare system.

The House Energy & Commerce Committee and the New York Attorney General are also investigating the companies’ questionable practices regarding Vytorin.

Deepak Khanna, general manager for Vytorin told The Wall Street Journal that:

"Our sales force and medical-affairs group have been well prepared about what this study is and how to talk about it." The companies plan to aggressively take their case to managed-care plans and pharmacy-benefit managers who make decisions affecting the use of prescription drugs.

Merck and Schering are also discussing when to restart Vytorin advertising.

Schering derives almost 60% of its profits from Vytorin and Zetia. This was a key driver in the S&P placing Schering’s long term ratings on credit watch Monday. Their other big sellers are Nasonex (nasal allergies) and Remicade (for inflammatory disorders affecting the immune system, such as rheumatoid and psoriatic arthritis, Chron’s disease and ulcerative colitis). Schering doesn’t plan on doing an acquisition as the company is still paying for its $16 billion purchase of Organon Biosciences. Schering’s only positive is that it will be awhile before many of its major products face patent expiration.

S&P left Merck’s rating unchanged due to its more diverse pipeline. However, numbers can be deceiving. Monday, Merck suspended further patient enrollment in its 900 participant study of Cordaptive, a cholesterol drug awaiting FDA approval. Merck is using the same method to measure patient response that it used in the Vytorin Enhance trial.

Despite the ad revenues, there have been media stories criticizing cholesterol as a big pharma marketing phenomenon. BusinessWeek put Cholesterol on the Cover, and a February 12 Wall Street Journal story looked at the growing medical evidence that your brain needs cholesterol.

Medical trends tend to operate in extremes. As the evidence continues to grow that lowering cholesterol not only fails to prevent cardiac events, but also may be contributing to the rise in memory disorders, “what’s your number?” will refer to your IQ instead of cholesterol.

Disclosure: none

Comments

[technicolor1935]

Objectively, you have to ask yourself, why all the Cardiologist hoopla about Vytorin not reducing corroded artery plaque in pre selected genetically compromised patients when such was never an espoused claim of the Rx, nor that or any competitor? Furthermore, Vytorin's goal of reducing LDL-C was met, and better than that of any competitor, but such is being totally ignored as having no physiological or medical event importance whatsoever. True, Merck & Schering may have wanted to obtain plaque reduction as a yardstick indicator objective, but such was, at worst, misplaced hubris, not misdirection or fraud.

In the 23rd of March 2006 issue of NEJM, Dr J.Cohen and colleagues of the Texas Southwestern Medical Center, Dallas, published their findings on individuals with the PSCK9 genetic variant. The PSCK9 genetic variants seem to confer lower LDL-cholesterol levels.

Their study is part of the longitudinal "Atherosclerosis Risk in Communities" or ARIC study. They studied 12,887 subjects (black and white) with the PSCK9 genetic variant. There were 2.6% blacks and 3.2% of whites who had a mutation of the PSCK9 gene. The 2.6% of blacks had 28% lower baseline LDL-C when compared to those blacks without the mutation. As for the whites, 3.2% of them had the gene mutation and their LDL-Cholesterol levels were 15% lower.

However, after 15 years, this 28% lower LDL-C in the blacks, translated to a 89% CAD reduction. In the whites, the 15% LDL-C reduction translated to a 47% reduction. Long term (15 yrs) LDL-c lowering may have greater benefit than short term (5 yrs). Perhaps someone taking a moderate LDL-C lowering agent, when taken over 10-15 years, may have the same, if not better CAD reduction when compared to high dose superstatins with their risk of side-effects, and, as a result, significant CAD reduction due to lower LDL-C levels. Hence, the efficacy of Vytorin.

[Tony D.]

I agree with the above comments. Both my wife and I take Vytorin with excellent results. Merck is being unfairly attacked in the media. Why are so many people intent on dragging down this great company whose pioneering efforts have brought so many life-saving medicines and vaccines to market? Let's get all of the facts. God forbid that this latest "episode" will only serve to encourage more lawsuits. Merck has always been a leader in its field and needs more support in order to pursue its attempts to defeat such scourges as heart disease, cancer, and other life-threatening diseases. Generic companies are always quick to pounce upon the opportunity to profit from the research efforts of companies like Merck while investing zero in research of their own.

[Bob C.]

I agree whole-heartedly with the above 2 comments. What needs to be done is that Dr. Steve Nissen needs to be investigated. Everybody takes his comments as the "holy grail" of medicine. Let's examine the connections he has and what money is given him from sources within the healthcare industry. Maybe he doesn't have high regard for certain pharma companies? Whatever the case, Grassley needs to do a complete review of Nissen. If we want to fully understand Nissen's reactions, we need to understand his motives.