16 April 2007

Ranolazine: Safety First

I'm sure you've heard of a company in Silicon Valley by the name CV Therapeutics. CVT has a product on the market by the name of Ranexa (generic name of ranolazine). This is a drug developed for people with angina. Just one hitch: it's associated with a prolonged QTc interval. This means the heart in a patient using the drug has some risk of developing an arrhythmias. Not a small problem in such a patient population. The concerns about this adverse event (nice understatement) have restrained the medical community in the United States from using this product--less than $25 million was sold last year in the U.S. The company is burning about $300 million per year, and it has about a year's worth of cash on hand, so unless the drug catches fire in the marketplace, it seems likely there will be some layoffs for the company. After a recent trial result missed its efficacy endpoint, Wall Street practically wrote the company off for the corporate dead. (Rumor has the trial costing nearly $100 million.) It's true that the same trial didn't confirm a safety problem, but such trials are never good for those purposes. If they were, then the safety problem is so onerous, the drug wouldn't stand a chance in the market.

One might think that the management of CVT would have done everything possible to position the drug to be accepted by the medical community. And one would wrong in that thinking. As a recent paper in Clinical Therapeutics (2006;28:1996-2007) noted, there hasn't been one cost-benefit analysis of the product published. It appear there is no registry of ranolazine users, either. Such registries are commonplace in the pharma industry today, and with a large registry of users followed for considerable periods of time, one can get enough statistical power to examine adverse events like QTc prolongation or arrhythmias. Certainly better than in a randomized trial! But CVT's management doesn't appear think such basic tools are part of risk management--and there's no clear reason. It also doesn't provide for much outside, independent evaluation of its risk management program to assess the effectiveness of the program. Let's hope the FDA is on the ball with this one, since it's the only one able to force any changes in the program.

Even more intriguing, the grapevine has the company just getting around to hiring a VP for drug safety. Kind of like closing the barn door after the horses are long gone. And yet the CEO has the time to serve on the Board of Directors of two other companies--Metabolex and Maxygen. Maybe he's pretty confident that the lack of sales of this product are a minor problem associated with 2006 and that the safety issues are now going to disappear?

Stay tuned--we're keeping track of this situation. Very curious indeed.

No comments: