Brave Neuro World - Pharmaceutical Executive


Brave Neuro World
Cosmetic neurology is a massive off-label market, but pharma has tended to look the other way. FDA may be about to change all that

Pharmaceutical Executive

FDA and the Road to Approval

That argument may also carry the day at FDA under its current leadership. Commissioner Margaret Hamburg and Deputy Commissioner Joshua Sharfstein are both physicians who have displayed a striking fidelity to science (rather than politics or other influences) when setting policy in their careers as public-health officials. Given the fact that a growing segment of the public is regularly mind-hacking with off-label and black market CEs, it would seem logical for them, at the very least to call for more science, including clinical studies to assess the risks and benefits in healthy consumers.

Not surprisingly, most researchers also back more science, even those like Minzenberg who question whether cosmetic neurology is viable. "We know how these drugs work at the cellular level, but there's still a lot we don't know," he says. "What is their effect on the entire circuitry of the brain? How does that translate into cognitive function? What are the unintended consequences?" Clinical trials could help identify potential trade-offs in a drug's effect or potential links between individual "patient" differences and variations in response.

FDA denied Pharm Exec's request to interview Russell Katz with an email that read: "We cannot comment at this time on what the regulatory pathway for CE drugs might be. Each new drug application is judged on its own merits." Yet Katz offered some clues in his Journal of Alzheimer's Disease comments regarding increased safety monitoring of off-label use. The drug industry, he said, can expect to be required to conduct additional Phase III trials for all cognitive enhancers, both those that are submitted for approval specifically for use in healthy or aging people and those that are simply likely to be prescribed off-label for such use. These studies will test the compound in a representative healthy (albeit sleep deprived, jet lagged, or aging) population, and a squeaky-clean safety profile will be expected. In short, the onus for more science will fall to pharma. Gone are the days when Cephalon could reap the profits of the 90 percent of Provigil prescribed off-label while mostly evading accountability for knowing the potential dangers posed to consumers.

Meanwhile, the American Academy of Neurology last year gave its stamp of approval to the off-label prescribing of cognitive enhancers to healthy people, arguing that society will come to endorse CE as akin to cosmetic surgery because its benefits will outweigh its risks. In February, Britain's former health minister and surgeon Lord Ara Darzi announced that he is launching such a clinical study at Imperial College London. "We know people are doing these drugs anyway, but we don't know about their long term safety," Barbara Sahakian, a neuroscientist involved in the project, told the London Times. "The government has a responsibility to think about what they should do about that. Maybe they should be letting pharmaceutical companies brand these medications via a safe route. Wouldn't that be better?"

On March 29, Cephalon announced that it had received a "complete response" letter from FDA—at best, postponing; at worst, denying approval of Nuvigil for jet lag. The agency reportedly found the "robustness" of some data wanting. The stimulant's benefits, although statistically significant, were admittedly slight. (For example, the Nuvigil group took an average of 9.7 minutes to fall asleep the first day after their transatlantic night flight, compared to the placebo group's 3.4 minutes.) FDA's cost/benefit analysis may have concluded that six extra minutes of sleeplessness may not be worth the increased risk of headaches, palpitations, anxiety, and other side effects.

Still, cosmetic neurology, however controversial, appears destined to come in from the cold. After all, a technologically wired global economy demands a chemically wired workforce. If not by Nuvigil, the road to regulatory approval will be paved by the first drug for the aging brain. Or FDA will carve out exceptions for a Provigil-type drug for soldiers, air-traffic controllers, surgeons, and other high-risk occupations, followed by a gradual expansion to the general population. Or China will pioneer approval.

Brain-Boosting Takeouts
For even as neuroethicists fret over issues like unequal access to enhancement's competitive edge and how that edge may have a coercive influence, the iron law of ever-increasing productivity must be obeyed. In the end, we may not much like this new world—it is certain to contain many more accountants and far fewer artists than the old one. But fear not, a pill may be coming to manage that low mood, too.


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