The Fix's Week in Science: February 27, 2012
- FDA Set to OK First Diet Drug in More Than a Decade[The New York Times]
For the first time in 13 years, we may get a new prescription diet pill. Qnexa got a thumbs-up from the FDA’s advisory panel, following a rejection two years ago. Why the reversal? Vivus, the biotech that developed the drug, produced new safety data—more patients, a longer study. But the approval weather at the FDA has also likely brightened dramatically with the government’s anti-obesity campaign and doctors' clamor for a chemical weapon against dangerous girth. “There is an urgent need for better pharmacologic options for individual patients,” says Dr. Elaine Morrato, an assistant professor at the University of Colorado, who voted no in 2010 and yes now. “I believe that Qnexa demonstrated a meaningful efficacy benefit and that there are consequences to nontreatment of obesity.”
Qnexa mixes two already-available drugs: phentermine, a non-amphetamine stimulant, and topiramate (Topamax), an anti-seizure drug that's being widely tested and even prescribed for addiction to alcohol, cocaine and other substances. Both have baggage. Memory loss and other cognitive side effects won Topamax street names like “Dopamax” and “Stupamax,” while phentermine’s record is also checkered—it was the “phen” in fen-phen, the diet pill yanked from the market in the late ‘90s after healthy young women started dying from heart attacks and respiratory failure. Although the fen, not the phen, was found guilty, it’s rare for drugs to come back from a guilt-by-association taint. In fact, it was that scandal that turned the FDA into a place where anti-obesity drugs go to die.
In 2010 the FDA viewed Qnexa's benefit—weight loss averaging 10.6 pounds, much of which was regained when people stopped popping the pill—as too small to make up for its incidence of heart problems and birth defects. Yet new data suggests that the health improvements linked with even modest fat shedding are more substantial and sustained than expected. But so was the incidence of increased heart rate—a risk signal for heart attack and stroke.
What’s to keep Qnexa from becoming another fen-phen? First, the FDA is likely to approve Qnexa this spring with serious restrictions. The drug is expected to be labeled for use only by people with a body mass index of 30-plus (“obesity”), or with weight-related problems like diabetes. Vivus has also committed to doing a large clinical safety trial and to limiting access by distributing the product only to mail-order pharmacies (no online sales). Yet restrictions have a way of turning into recommendations once a drug is out on the market, with drugmaker commitments often forgotten. With both phentermine and Topamax available as cheap generics, as many as 70% of all obesity specialists are already writing off-label scrips for the two drugs—to the dismay of Vivus, which will have to market the hell out of its new brand to persuade consumers to pay several bucks rather than several cents per dose.
- The Reality of Red Wine as a Medicine [Addiction]
Given the publicity about the potential health benefits of red wine, it’s fun to wonder whether fermented grape juice would ever be approved by the FDA as a medication. The outcome of this hypothetical rests, as all drug approvals do, on a risk/benefit analysis. On the one hand, there is alcoholism, suicide, automobile accidents, to name just a few risks; on the other, increased longevity, but only if you can drink as if you were dosing—a single glass, every day, for life. So says Canada’s Center for Addiction and Mental Health in a comprehensive analysis of 44 is-red wine-beneficial? studies published in the journal Addiction.
The researchers focused only on heart attacks (a total of 38,627 among 957,684 people) and found that those who downed a drink a day (no more, no less) lived the longest, with the fewest cardio-related problems. Yet given that only 5% of North Americans exhibit this drinking pattern (binge drinking is more common), adherence to this drug would plainly leave the FDA less than impressed.
- Animal Deworming Drug in Cocaine—and in its Users [MedPage Daily]
Care for some levamisole with that line of coke? Probably not—levamisole is an anesthetic used in animals for deworming, but banned in humans because of toxicity. Yet odds are slightly better than 50-50 that if you use cocaine, some of that creepy chemical is coursing through your blood. Last year, the DEA reported that 82% of the white powder that came their way contained the vet med—a favorite cutting agent among dealers because it's bright white, adds bulk and enhances coke’s euphoric effects.
Given such high prevalence, the results of a poster presentation at the Society of Critical Care Medicine meeting this week may pass for good news. Out of some 46 cocaine users, 24, or "just" 52%, had levamisole-positive blood tests; of those, there were three cases of tachydysrhythmias (abnormal heart rhythm) and three of vasculitis (blood-vessel inflammation), serious side effects of the anesthetic.
- A New Target in Anti-Relapse Research [Science Daily]
Dopamine is the dope when it comes to the brain’s pleasure pathways—every reward-seeking activity from food to sex to drugs involves a spike in the neurotransmitter. Stimulants like cocaine, crystal meth and nicotine enhance dopamine either directly, by triggering its release, or indirectly, by blocking the neuron receptors that take it up. A study published in Biological Psychiatry sheds light on how dopamine may cause ex-smokers to relapse. During nicotine withdrawal, the brain can no longer produce enough of the feel-good chemical, although the so-called tonic dopamine feel disproportionately more than the so-called phasic version. That finding provides a more exact dopamine target with which to develop drugs that elevate tonic dopamine and offer resistance to relapse. Such a drug may well support recovery from other addictions as well.
- Hepatitis C Treatment Advances [FierceBiotech]
The next generation of hepatitis C treatments is on the way—sort of—with an all-oral combination of four drugs that would free patients for the first time from having to shoot up with alpha-interferon and risk its nasty side effects. Vertex announced decent data this week for its Phase II combo (11 of 46 patients virus-free in 12 weeks), taking advantage of Gilead's bad news last week that six of the 10 patients on its own all-oral four-drug mix saw their virus come roaring back after a four-week "cure." All you ex-injection-drug users with the liver-killing infection—hang in there, a new (better, safer, easier) treatment should be out by 2015.
- Elaine Morrato
- Center for Addiction and Mental Health
- red wine
- Society of Critical Care Medicine
- tonic dopamine
- phasic dopamine
- hepatitis C
- Biological Psychiatry
- Walter Armstrong