HEALTH -- February 22, 2012 at 2:11 PM EDT
New Weight Loss Pill Gets Second Look from FDA, Stirring Old Fears
Photo by J.B. Reed/Bloomberg via Getty Images
Update: 6:55 p.m. ET | An independent panel of medical experts voted 20-2 to recommend FDA approval of Qnexa. Agency officials will now deliberate and issue a final ruling later this year.
It was described as "a medication that works like no other medication" ... a drug that stood to be "the next blockbuster entry in the battle against excess weight." Eager to benefit, Americans popped pills and watched their waist lines. But most ended up disappointed.
The drug was Xenical. Now, 13 years later, it's the only FDA-approved weight loss medication on the market. On Wednesday, as an FDA advisory committee considers whether to expand that distinction to the drug Qnexa, some physicians are warning against the hype that accompanied Xenical's U.S. debut.
History has proven that quick fixes are rare in this field, they say. And too often, they're also dangerous.
According to Dr. Howard Eisenson, director of the Duke Diet and Fitness Center, much of the excitement over Xenical boiled away after its drawbacks became more apparent in the early 2000s.
"The benefits are nothing more than modest, and the tolerability has been low among patients," Eisenson said. "With Qnexa, I think it has some promise. But I'm not convinced I'm going to be able to use an adjective other than modest."
Just how modest? A two-year study of Qnexa involving 4,323 people showed an average weight loss of at least 10 percent of total body weight -- about three times the amount in the placebo group.
Not bad, right? Well ... not so fast. For some perspective, let's go back in time.
Before its official release in 1999, clinical studies of Xenical showed that a group of patients who took the pill in addition to maintaining a healthy exercise regimen and a low-fat diet lost 10 percent of their total body weight. Those on the placebo lost four percent.
Here's former NewsHour health correspondent Susan Dentzer's full report from 1999:
Still today, the potential benefits are significant enough to peak the curiosity of many of Eisenson's patients, he said. But their interest often ends when Xenical's potential side effects are revealed: bloating, flatulence, oily stools, and the need to run to the bathroom frequently.
"That doesn't happen to everyone, but it's enough to scare a lot of people off from even trying it," Eisenson said. It's also enough to have washed away any hope that Xenical would become a "blockbuster."
The storyline could be similar for Qnexa, which is a combination of two existing drugs -- the appetite suppressant phentermine and anti-seizure medication topiramate. Phentermine was once half of the infamous fen-phen weight loss drug that was pulled from the market due to suspicions that its other half, fenfluramine, was linked to high blood pressure and heart valve disease.
But to many, the FDA's primary concern with Qnexa is perhaps even more frightening than fen-phen's side effects: exposure to topiramate during pregnancy has been associated with a two- to five-fold increased prevalence of cleft palate in babies. In its new application to the FDA, drug manufacturer Vivus is seeking approval with labeling that would prevent women of child-bearing age from using it.
Eisenson and others who spend their time helping severely overweight patients say that Vivus has a valid point -- that these drugs also need to be viewed in perspective. Because for some patients, they say, the weight loss pills can work remarkably well.
"In the hands of the right physicians and the right patients, they can be safe. There are people who need them -- people who have tried everything else," said Joseph Nadglowski, president of the Obesity Action Coalition. "We would be open to the FDA limiting distribution to make sure they go into those right hands to start, but the agency needs to take that balance into consideration."
The debate has raged for decades -- beyond Qnexa and Xenical, even beyond the formation of the FDA. And unfortunately, its history is also one fraught with disaster, said Dr. Russell LaForte, a weight loss specialist at the University of Texas Medical Branch in Galveston, Texas.
For more context on the FDA's apprehensions, LaForte takes us through a number of those disasters, starting in the late 19th century.
Initial efforts focused on ways to increase metabolism. In the 1890s, with advances in organic chemistry, thyroid hormone could be extracted from animal thyroid glands and fashioned into a medication designed to treat thyroid insufficiency. It wasn't long before these medications were used for obesity. This use soon fell into disfavor, however. Overuse of thyroid hormone extract leads to hyperthyroidism, which, when advanced, can cause heart failure, extreme elevation of body temperature (hyperthermia) and death. Milder chronic use eventually leads to osteoporosis and increases fracture risk.
The next medication to gain traction was 2,4-dinitrophenol (DNP) in the 1930's, which directly increases metabolic rate by increasing the body's generation of heat. Chronic use for more than a few months leads to cataracts and damage to the nervous system. Overdoses led to a number of deaths, since it has an even greater ability to elevate body temperature than thyroid hormone. The fledgling FDA gained new power in 1938 and was able to put pressure on manufacturers of pharmaceutical products. By 1940, DNP was no longer being marketed due to these ill effects and pressure applied by the FDA. However, as war spread through Europe and engulfed the U.S., regulation of the pharmaceutical industry drew less government attention.
Chemistry took no such break. A variety of medications designed to treat other diseases slowly gained some acceptance through the 1940s and 1950s. These included heart medications such as digitalis and amphetamines. In spite of some ill effects and deaths, these agents and more like them appeared in the 1960s and were increasingly promoted for weight loss. Eventually, two or three pills were prescribed at a time for weight loss, with an extra sometimes added to mask the side effects. Since the medications were colorful, the term "rainbow pills" caught on.
By 1959, however, interest in reform was rising. Due to advertising and marketing practices, the pharmaceutical industry had drawn the special attention of Estes Kefauver, head of the Senate subcommittee on anti-trust and monopoly. Soon after they began the hearings, Thalidomide, a sleeping pill, was shown to cause a large number of birth defects, mostly in Europe and Canada. Kefauver took this example and pushed for an amendment to the Food, Drug, and Cosmetics Act, and by 1963, the FDA required all manufacturers to provide scientific evidence of safety and efficacy. "Rainbow pills" stopped being promoted as Senate investigations were held during the 1960s into deaths attributed to them, often of young, otherwise healthy people. It turned out that heart drugs and speed don't mix. The FDA restricted amphetamine prescriptions and "banned" its use as a weight loss aid in 1979."
In the mid 1990's, a new approach to obesity developed as the role of serotonin became better appreciated. A serotonin stimulating drug, fenfluramine, was combined with the stimulant-like medication phentermine. The combination resulted in greater weight loss than either alone. A form of fenfluramine, called dexfenfluramine, was isolated and had great weight loss success as well. Both fenfluramine and dexfenfluramine were FDA-approved and had supplied the scientific proof of efficacy and safety as required by law. For a few years, it appeared a powerful tool to fight obesity had arisen, and many millions of prescriptions were written. But heart valve and cardiopulmonary pressure problems occurred in some patients receiving these drugs. It was difficult, if not impossible, to scientifically prove the drugs were to blame. But the association of the findings with the use of the drugs proved to be too much. Both fenfluramine and dexfenfluramine were removed from the market in 1997. (Read a transcript of the NewsHour's report from 1997 here).
Soon after they were removed, another serotonin stimulating drug, sibutramine was approved. The sibutramine labeling warned against its use in patients with known heart disease and cautioned supervision of patients with high risk for heart disease. However, eventually the issue of whether sibutramine actually decreased cardiac events in patients older than 55 with heart disease or at very high risk of heart disease was studied. According to the FDA, there was a small increase in nonfatal heart attacks and nonfatal strokes in those heart patients receiving sibutramine. It was voluntarily withdrawn from the U.S market in 2010, though it is still found as an illegal ingredient in some over-the-counter weight loss products in the U.S.