The demise of Fen-phen dealt a body blow to hopes for an obesity pill that is actually effective. Unfortunately, the fen in Fen-phen, fenfluramine, caused grave pulmonary hypertension and heart valve problems. The phen part of the drug, though, was apparently just an innocent bystander. And now phen (phentermine) has resurfaced in a new pill that has posted some amazing results in Phase III clinical trials. Patients who were treated for 56 weeks with the new drug, Qnexa, lost an average of 14.7 percent of their weight, or 37 pounds.
Qnexa, produced by Vivus, is a low dose formulation of immediate release phentermine combined with controlled release topiramate, otherwise known as Topomax. Topiramate, which was approved in 1996 for treating epilepsy, and more recently as a migraine preventer, increases satiety, or the sense of being full. Phentermine reduces appetite, and the combination of the two is apparently pretty potent.
Topiramate apparently increases satiety by enhancing the activity of GABA (gamma-aminobutyrate), a calming neurotransmitter that inhibits food intake.
Phentermine (pheny-tertiary-butylamine) is a sympathomimetic amine, which means that it produces effects similar to those caused by stimulating the sympathetic nervous system. By provoking the hypothalamus to release norepinephrine, a neurotransmitter that signals fight-or-flight, it reduces appetite, which is associated with the rest-and-digest response of the parasympathetic system.
The combination of a satiety increaser and an appetite reducer could be potent because, according to the New York Times, food consumption is a balance between a food-seeking system, which says “eat,” and a satiety system, which says ”stop eating.” When either system is out of whack, weight control problems can result. The Chinese hamster, for example, which lives in the desert, completely lacks a satiety system. When it does manage to find some food, it keeps eating until the food is gone. Put that hamster in an environment with plenty of food, and you have one fat hamster.
Last month, Vivus announced the results of two year-long double-blind Phase III studies that evaluated the safety and effectiveness of Qnexa in more than 3,750 patients across 93 sites. The trials evaluated three doses of Qnexa: 15 milligrams of phentermine and 92 milligrams of topirimate; 7.5 milligrams of phentermine and 46 milligrams of topirimate, and 3.75 milligrams of phentermine and 23 milligrams of topirimate. The results demonstrated a favorable safety profile, improved glycemic control, and significant improvements in cardiovascular and metabolic risk factors. But the real kicker was the weight loss.
The average weight loss for patients who completed the first study was 37 pounds with full-dose Qnexa and 18 pounds with low-dose Qnexa, as compared to six pounds in the placebo group. Sixty percent of the full-dose patients who completed the study lost at least 10 percent of their baseline weight, and 43 percent lost at least 15 percent. The results of the second study were very similar.
There were no drug-related serious adverse events, and the most common side effects were tingling, dry mouth, altered taste and constipation.
An earlier Phase III clinical study showed that treatment with Qnexa not only lowered A1c’s in diabetic patients, but also arrested the progression to diabetes by preventing increases in A1c in obese patients who were not yet diagnosed with type 2.
Vivus plans to file a New Drug Application with the FDA by the end of 2009. A New Drug Application, or NDA, is the means by which drug sponsors formally propose that the FDA approve their new pharmaceutical for sale and marketing.
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