June 17, 2008
Glaxo's Delay on Restless Legs Drug
GlaxoSmithKline is complaining that the Food and Drug Administration delayed in approving its once-a-day version of its Parkinson's disease drug, Requip (ropinirole). The drug, which mimics dopamine in the brain, has primarily been promoted as a treatment for restless legs, a disease invented by the company's marketing department.
According to this morning's Wall Street Journal, company executives told an investors conference that the FDA failed to give the drug priority status, which resulted in the drug coming to market after its patent on the thrice-daily version expired. The FDA is giving short shrift to drugs that are not innovative, the story suggested.
Let's explore this one a bit further. A once-a-day version of a drug that substitutes for a thrice-daily version isn't hard to make (it usually involves a minor modification of the original molecule that makes it harder to metabolize without detracting from its effectiveness). And, while it won't win anyone the Nobel Prize, a longer-lasting version does offer some benefit to patients in terms of convenience and increased compliance (patients are more likely to remember to take their pill every morning than every morning, noon and night).
So do companies rush to bring this level of "breakthrough" to market? No they don't. Whether it is for a phony disease like restless legs or a significant use like Parkinson's, they keep the long-lasting version in the wings until the patent expires on the original drug. In fact, they try to time their passage through the FDA so that it arrives in the marketplace just a few months before the old patent expires. This marketing-driven strategy seeks to wean physicians (and their patients) off the soon-to-expire patented drug by getting them to prescribe the newer version (using increased compliance as the selling point).
How long does it take to get regulatory approval for the newer version (including the necessarily clinical trials)? Hard to say, but obviously a lot shorter than the 10 to 12 years that it takes to get the original molecule approved. Five years is not an unreasonable estimate (only 12 to 18 months of which is after the completed application and data are submitted to the FDA for non-priority drugs).
A quick check with the Orange Book (the FDA's listings of medicines and their approval and patent expiration dates) shows that the original Requip was approved in 1997. Its key patents expired last year and in May of this year.
Glaxo knew the minute the drug came on the market that it could develop a version that only needed to be taken once a day. But did it rush into the lab to develop this innovation? Or did it slow its development program so that it could be marketed in time to replace the old drug when the patents expired? The evidence clearly suggests the latter.
So who is really to blame for the "delay" in getting Requip XL (the name given to once-a-day ropinirole) to market? Is it the FDA, or a corporate strategy that would sacrifice patient convenience and compliance in the name of bolstering the bottom line?
Posted by gooznews at June 17, 2008 08:13 AMWhile the prevalence of RLS can be debated -- and the enthusiasm with which both Requip and Mirapex have been marketed for the syndrome is undeniable -- the proposition that RLS was "invented by [GlaxoSmithKline's] marketing department" won't survive 30 seconds of fact-checking.
The syndrome was first described by the English physician and anatomist Thomas Willis in 1672. In the 19th century, both Theodor Wittmaack (1861) and G.M. Beard (1869) published descriptions; and in 1945, Karl Axel Ekbom published a report of 34 cases (Acta Medica Scandinavica, Stockholm, Supplement, 1945; 158: 1-123.) containing the canonical clinical features now incorporated in the 2003 NIH Consensus Panel criteria (Sleep Med 4 (2): 101–19).
Not even the all-too-easily-trivializable name of the condition can be hung on the pharma industry's door. Although neurologists and sleep specialists for many years referred to the condition as Wittmaack-Ekbom syndrome, it was Ekbom himself who first used the term "restless legs," and as eponymous disease names fell out of favor in medicine, the RLS nomenclature was adopted by sleep specialists who now treat the majority of cases.
A reasonably good summary of current knowledge about the disease can be found at http://en.wikipedia.org/wiki/Restless_leg_syndrome.
It is worth noting, by the way, that much of the impetus for research into the application of dopaminergic agents such as ropinirole and pramipexole (which were originally developed to treat Parkinson's Disease) came not from the companies themselves (The overall market is no more than 8 million Americans.) but from patients and sleep specialists, who typically describe the condition as "tormenting."
The industry as a whole is vulnerable to the critique you raise regarding "lifecycle management" through debatably meaningful modifications of molecules long on-market with far fewer clinical benefits to patients than commercial benefits to the companies. But that critique is only weakened, in my opinion, by commingling it with charges (in this case, unfounded) of "disease mongering."
Posted by: Bruce Grant at June 24, 2008 02:28 PMI agree with Bruce -- surprise! The main issue here is the drug industry's "life cycle" management strategy vs. timely development of new and better versions of drugs, even if the drug has been promoted for something many believe is a made up medical condition. Well, maybe not made up, but overhyped as something many more people may suffer from than is justified by the data.
Posted by: John Mack at June 25, 2008 03:09 AM