Diet drug Qnexa awaits FDA OK amid safety concerns

Some things may indeed look better the second time around, but why would that be the case for a new diet drug that's poised to become the first such drug approved by the Food and Drug Administration in more than a decade?

The proposed prescription medication Qnexa (kyoo-nek-suh) from Vivus Inc. of Mountain View, Calif., helps dieters lose 10% of their weight when used in combination with diet and exercise.

Yet it was rejected on a 10-6 vote the first time it came before a government advisory panel, in 2010, because of safety concerns. But when the medication returned for another review in February, the advisory committee gave it near-unanimous approval (20-2). Because the FDA often follows the advisory panel's advice, Qnexa is likely to get FDA approval, probably by mid-April.

Supporters of Qnexa say that not only does it produce dramatic weight loss, but it helps reduce diabetes and lowers blood pressure and other cardiovascular risk factors.

Cast Your Vote

But critics are charging that too many safety questions remain. Research shows Qnexa caused an increased heart rate in some patients who took a high dose, and it increased the risk of cleft lip in the newborns of expectant mothers who took the drug.

So what led the FDA advisory committee to change its view of the drug between 2010 and 2012?

"We had more data to understand the benefits of the weight loss compared to the health risks in areas of greatest concern: the risk of birth defects and the effects the medicine had on cardiovascular disease," says Abraham Thomas, chairman of the second advisory committee and a member of the first committee. Thomas is head of endocrinology at Henry Ford Hospital in Detroit.

Diet drugs in the past and in the pipeline

Here�s a look at the current diet drugs and the history of some weight-loss medications.

On the market now:
Two prescription drugs used to treat obesity include phentermine, which suppresses appetite; and orlistat (Xenical), which keeps some dietary fat from being absorbed by the intestine. Orlistat is sold in a lower dose over-the-counter as Alli.

Pulled off the market:
In 1997, two diet drugs were pulled from the market � fenfluramine (part of the popular fen-phen combination) and dexfenfluramine (Redux) � because of concern over heart-valve problems.

In 2010, Abbott Laboratories removed sibutramine (Meridia) from the market because of concerns of an increased risk of heart attacks and strokes.

Didn�t get government approval:
In 2007, an FDA advisory panel rejected the experimental diet pill rimonabant (Acomplia) from Sanofi-Aventis, which decreased people�s drive to eat, after hearing testimony that it increased the risk of suicidal thoughts, even in patients without a history of depression.

FDA reviewing now:
In mid April, the FDA is expected to decide whether to approve Qnexa from Vivus. When used in combination with diet and exercise, patients lose about 10% of their weight on the proposed diet medication.

Seeking approval:
In May, an FDA advisory committee will discuss the safety and efficacy of the anti-obesity medication lorcaserin from Arena Pharmaceuticals. It was rejected by an early FDA advisory panel in 2010.

In 2011, the FDA asked for a clinical trial on the cardiovascular safety of Contrave from Orexigen. Contrave combines two drugs now on the market � bupropion, an antidepressant and smoking cessation medication, and naltrexone, currently used for alcohol and opioid addiction. The diet pill works to fight food cravings and improves the ability to control eating. Drug trial will start late in second quarter of 2012.

Source: USA TODAY research

Although heart rate went up slightly in some patients, blood pressure went down, he says. There are health benefits for patients losing 5% to 10% of their weight, which many people can't do by diet and exercise alone, he says.

The committee was reassured that the FDA working with Vivus would have appropriate package labeling and a risk-reduction strategy to prevent pregnant women, or those planning to become pregnant, from taking the medication, Thomas says.

The committee thought the benefits of Qnexa were "great enough" that the medication could go on the market, and then the company could do a larger clinical post-market trial to investigate whether there is more cardiovascular disease when people take the medication for several years, Thomas says.

But Sidney Wolfe, director of the health research group at Public Citizen, a consumer group, says that the risks outweigh the benefits. "We are strongly opposed to approving it. This idea that there is a magic bullet that will knock your hunger out, but not do other kinds of damage, is ridiculous."

He thinks the advisory committee approved the diet drug because members "felt there was a desperate need for a new diet drug even though many other ones had come and gone because of safety concerns."

About two-thirds of people in this country are overweight or obese. Obesity increases the risk of heart disease, type 2 diabetes, some types of cancer and many other health problems.

Most panel members voting for approval of Qnexa said safety concerns about the medication should be thoroughly studied as soon as possible after approval, but Wolfe says all of the potential risks should be investigated before Qnexa is "unleashed on a mass market of hundreds of thousands of people."

The drug 'produces weight loss'

Qnexa is made up of two other older medications: the appetite-suppressant phentermine and the anti-seizure medication topiramate, which is sold under the brand name Topamax. The latter is used to treat epilepsy and migraines. Some physicians already prescribe the two drugs together for weight loss in what is called an off-label use, which is the practice of prescribing medications for an unapproved indication.

Qnexa is designed for people who are obese, which is roughly 30 or more pounds over a healthy weight, or those who are overweight and have other weight-related health issues such as high blood pressure, type 2 diabetes or high cholesterol.

The company's research on Qnexa shows that people lose 10% to 11% of their starting weight in a year. "The efficacy of this drug is not the issue � it produces weight loss," says Tim Church, a researcher at the Pennington Biomedical Research Center in Baton Rouge and an adviser to Vivus.

The studies showed the high dose of the medication increased heart rate by 1.6 beats per minute, Church says, but it also lowered blood pressure, triglycerides (blood fats), C-reactive protein (another heart disease risk factor) and fasting blood sugar. "It dramatically reduces the risk of diabetes."

The two medications that make up Qnexa have been used by millions of people, Church says. "If these are dangerous, why aren't we hearing things about them?"

But Wolfe says that hunger is deeply embedded in the body, and "when you knock out hunger with a drug, you affect many other functions in the body."

He says the studies on Qnexa show that the drug increases heart rate and that five patients on the diet pill had non-fatal heart attacks during the research, while none of those on the placebo had heart attacks.

Wolfe points out that several previous diet drugs have been withdrawn from the market, including sibutramine (Meridia) because of evidence of an increased risk of heart attacks and strokes, fenfluramine and dexfenfluramine (Redux) because of concern over heart-valve problems, and ephedra because of heart attacks and strokes.

Pushing for more trials

Now there's a new wrinkle in the Qnexa story. Last week, the same FDA committee voted 17-6 to require that obesity drugs undergo clinical trials to ensure they don't increase cardiovascular problems, even if there's no suggestion of heart disease risk during the drug's development, Thomas says. Those trials might take place before or after the drug's approval. If the FDA follows the panel's advice, it will add to the cost of getting obesity drugs approved.

Will this latest advice to the FDA affect the agency's decision on Qnexa?

Thomas doesn't think so because Vivus already had an indication of possible heart risk with increased heart rate and is now planning a trial to investigate cardiovascular issues. But it will be up to the FDA to decide whether the trial needs to be conducted before or after Qnexa is approved, he says.

Wolfe says he doesn't know whether the committee's advice will affect the approval.

It depends on how serious the FDA is about following the panel's advice, which hasn't been implemented into guidelines yet, he says. On one hand, these standards were not in place when Vivus started its drug trials for Qnexa, Wolfe says. On the other hand, the FDA's job is to make sure that when a drug "comes out the door, the benefits exceed the risks," he says.

Vivus has declined to comment, saying it's in a "quiet period" before the FDA makes its decision on the drug.

A need for diet medications

Vivus has been having discussions with the FDA on doing a large-scale follow-up study on the pill's effect on cardiovascular risk factors.

Cardiologist Michael Lincoff, vice chairman of cardiovascular medicine at Cleveland Clinic, is helping Vivus design a post-marketing drug trial. He says a study of 11,000 people is designed to investigate cardiovascular outcomes. "We feel that a drug that reduces weight, blood pressure, triglycerides and the severity of diabetes will address the unmet needs in the treatment of cardiovascular disease."

He says the drug's effect on heart rate "was very mild" and that heart attacks among people taking Qnexa in the drug's earlier studies were a "tiny number and probably a result of chance."

The new study will take two to three years, he says. It'll be expensive, "and the reality of the marketplace is they will need an income stream to fund a trial like this."

Lincoff says there is a need for diet medications such as Qnexa. "We know that, on average, a person who follows a diet and exercise plan will lose 3% of their body weight, and there is no good medical therapy to help them lose more."

Qnexa suppresses appetite so people are more likely to reduce their calorie intake and lose 10% to 15% of their weight, Lincoff says. "For a 200-pound person, that's 20 to 30 pounds. That's no trivial thing."