Obesity and birth control

The weight loss drug Qnexa

The Wall Street Journal - Business
July 13, 2010
By Jennifer Corbett Dooren Of DOW JONES NEWSWIRES

FDA Says Obesity Drug Works But With Side Effects

“WASHINGTON (Dow Jones)--The U.S. Food and Drug Administration said Tuesday that a proposed Vivus Inc. (VVUS) weight-loss drug resulted in "significant" weight loss, but the agency raised questions about the drug's long-term side effects.

The questions from the FDA aren't related to Qnexa's effectiveness, which has been proved in multiple clinical trials, but rather to the side effects of a drug that the agency is assuming may be taken indefinitely. Specifically, the panel pointed to increases in anxiety, sleep disturbances and depression, and debated usage by pregnant women.

Qnexa faces a review by the FDA's endocrinologic and metabolic drugs advisory committee Thursday. The panel of non-FDA medical experts will vote then on whether it thinks Qnexa should be approved by the larger FDA in a decision expected by late October.

Tuesday, the FDA posted its review of the product, which totaled 248 pages, on the agency's website.

Shares of Vivus rose 12.4% to $11.98 in early trading Tuesday. Wall Street analysts said the documents weren't particularly negative in their tone or content, but they warned that there remains a great deal of uncertainty about the panel's ultimate outcome.

A Vivus spokesman said the company looks forward to answering the FDA's questions at the panel, but he declined to comment further.

In its safety review of Qnexa, the FDA said it saw increases in heart rate among patients taking the drug but that the clinical significance of the finding is unknown.

The agency also said it saw increases in anxiety, sleep disturbances and depression among patients taking Qnexa compared to placebo but said the overall incidence of such side effects were low. The agency noted, however, that four to seven times as many patients taking the highest dose of Qnexa dropped out of the study because of anxiety-, sleep-, or depression-related side effects.

The FDA's review of Qnexa and the advisory committee meeting are being watched carefully by other companies with obesity drugs in development. Arena Pharmaceuticals Inc.'s (ARNA) lorcaserin will face an FDA panel in September, and Orexigen Therapeutics Inc.'s (OREX) Contrave is tentatively scheduled for a December panel review. The three drugs use different methods of damping appetite.

The other two stocks also rose Tuesday. Arena added 9.2% to $4.14, while Orexigen jumped 19% to $4.94.

The development of obesity compounds has been a tough area for companies since the fen-phen drug combination was taken off the U.S. market in 1997 after one of the medication's components was linked to heart-valve damage.

In 2007, an FDA panel unanimously rejected Sanofi Aventis SA's (SNY, SAN.FR) obesity drug Acomplia on concerns that the drug increased the number of psychiatric events, such as depression and suicidal thinking, among users. Sanofi later withdrew its application seeking FDA approval for the drug, and Pfizer Inc. (PFE) and Merck & Co. (MRK) scrapped plans in 2008 to continue developing similar drugs.

However, given that one-third of Americans are considered obese, companies successful at gaining FDA approval could tap a large market.

Qnexa is a controlled-release formulation that combines low doses of two older drugs: the stimulant phentermine, which cuts appetite, and topiramate, which increases the sense of feeling full. Topiramate is sold under the brand name Topamax by Johnson & Johnson (JNJ) to treat migraines and seizures.

Said the FDA: "Both drugs have reasonably well-established safety profiles because of their widespread use."

But because of the heart problems seen among patients taking fen-phen, the FDA looked at such side effects that might be attributed to phentermine and whether psychiatric side effects and birth defects potentially linked to topiramate would be seen among patients taken Qnexa. The agency noted that current evidence indicates the increased risk for heart-valve problems was attributable to fenfluramine and not to phentermine, one of Qnexa's components.

The FDA said heart palpitations were seen among 1.8% of Qnexa patients compared to 0.8% of patients taking a placebo. Patients taking Qnexa also experienced an increased heart rate. The agency said the clinical significance of the events "in terms of hard cardiovascular outcomes in the overweight and obese population is unknown."

The agency said it was concerned about a "large potential" for women to become pregnant while taking the drug as 34 pregnancies were seen in clinical trials despite instructions to use birth control and obtain a pregnancy test at each doctor visit. Of the 19 pregnancies carried to term, no birth defects were seen, although studies of topiramate in animals have shown it can cause birth defects.

Vivus is seeking a more relaxed birth-defects designation in its application, but FDA documents said the proposed labeling could be confusing to physicians and patients of child-bearing age. The FDA recommended that Qnexa be labeled as pregnancy category X, which means that the risk of using of the drug during pregnancy "clearly outweighs any possible benefit."

Two main clinical studies involving Qnexa were submitted to the FDA. The studies compared about 2,200 patients taking three doses of Qnexa to about 1,500 patients on a placebo, or fake drug, for 56 weeks.

The FDA said patients in the highest dose of Qnexa lost an average of 10.6% of their starting body weight, compared to an 8.6% loss for the middle-dose of Qnexa, 5.1% for the lowest dose and 1.7% for patients on placebo.”

Personal comment: My circle has no problem with obesity. Actually, with the calories we burn our problem is to keep our weight up healthily. I posted this article because we are seeing a lot of women coming into the clinic for help with weight reduction. And obesity and weight loss meds can decrease the effectiveness of hormonal birth control. In addition some weight-loss medications can cause birth defects. Weight loss can also decrease the effectiveness of cervical barrier methods of birth control because a woman’s reproductive anatomy changes with weight gain or loss. A diaphragm should be checked for correct size for every +/- 7 to 10 pounds of weight change and a cervical cap should be checked for every +/- 14 to 20 pounds of weight change. That’s why if a woman plans to lose a lot of weight our clinic recommends she use FC2 condoms until her weight stabilizes because they are safe, effective, aren’t weight sensitive and better tolerated by male partners.