After an all-day wait filled with media mishaps and investor speculation, the FDA this evening did, indeed, approve the Vivus prescription diet drug, which has been renamed Qsymia. The move marked the second time in two weeks that the agency endorsed a diet pill after 13 years in which no new fat fighters were approved, reflecting a desire by the FDA to balance a pressing need to combat obesity with concerns over side effects.
Indeed, the approval came with restrictions. Qsymia must not be used during pregnancy because the pill can harm a fetus. The contains phentermine, which is the surviving half of the fen-phen cocktail, and topiramate, the active ingredient in the Topamax seizure med, which generated concern over cardiovascular and teratogenic risks – specifically, cleft palates – and prompted the agency to reject the drug in 2010.
And since Qsymia can increase heart rate, the effect on patients at high risk for heart attack or stroke is not known. Consequently, usage in patients with unstable heart disease or stroke within the last six months is not recommended. Moreover, regular heart rate monitoring is recommended for all patients, especially when starting the drug or increasing the dose. There will also be a Risk Evaluation and Mitigation Strategy, or REMS, program for the pill.
“Obesity threatens the overall well being of patients and is a major public health concern,” Janet Woodcock, who heads the FDA Center for Drug Evaluation and Research, says in a statement. “Qsymia, used responsibly in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, provides another treatment option for chronic weight management in Americans who are obese or are overweight and have at least one weight-related co-morbid condition.”
The evening approval followed a rollercoaster ride of a day in which USA Today inadvertently broke an embargo and prematurely published a story declaring the FDA endorsement, even though the agency had not issued any statements (see this). The move embarrassed the drugmaker, which had still not issued an official statement nearly an hour after the approval was finally made. Meanwhile, nervous investors send Vivus stock down nearly 8 percent over anticipated disappointment.
The drug was evaluated in two randomized, placebo-controlled trials that included approximately 3,700 obese and overweight patients with and without significant weight-related conditions who were treated for one year. All patients received lifestyle modification: a reduced calorie diet and regular exercise, the FDA notes. And Qsymia was associated with a 10 percent drop in weight, which is more than Belviq, the recently approved Arena Pharmaceutical pill.
In clinical trials, Belviq demonstrated only modest benefits – patients lost about 3 percent of their body weight after one year when adjusted for placebo. In another measure, 47 percent lost at least 5 percent of their body weight after one year compared to 23 percent of patients who were on a placebo. Only this second measure met the FDA standard for approving weight-loss drugs.
Vivus has another advantage. The Arena pill is not expected to be available for several months, because Belviq must still be listed on the US Drug Enforcement Agency schedule for controlled substances, which can take up to six months. This suggests Qsymia has an opportunity to soak up the market, especially since the FDA allows patients to try different doses of the drug for up to 24 weeks before they are advised to discontinue treatment.
Arena, by the way, is also required to conduct six post-marketing studies, including a long-term cardiovascular outcomes trial to assess the effect of Belviq on the risk for major adverse cardiac events such as heart attack and stroke. The question, however, is whether these advantages are sufficient for Qsymia to dominate the market on a long-term basis. One analyst suggests this is possible.
“We believe that, given that neither compound provides all the answers to most obese patient needs (impressive weight loss, with a clean side effect/tolerability profile), the majority of obese patients wanting to try drug therapy will end up seeing both drugs, regardless of which one they take first. This assumption, together with the large potential market opportunity, makes us believe that there is room for at least two, if not more, sizeable drugs in the space,” writes Simos Simeonidis of Cowen in an investor note.
“However, we believe that Qsymia has a significant advantage over Belviq, given its considerably better efficacy. Qsymia’s safety will be an issue for some physicians (notably, the fear of birth defects among women who become pregnant), but Belviq’s carcinogenicity and valvulopathy signals, no matter how faint, may cast a bigger shadow over this compound and lead more prescribers and patients towards Qsymia, at least as their initial choice.”
A laggard among this new batch of diet pills is Contrave, which is being developed by Orexigen Therapeutics. The drug faces a prolonged regulatory hurdle and is scrambling to complete a large cardiovascular study that may yield FDA approval for its Contrave pill, but not until 2014 (read here).
Share and Enjoy
In a move that may herald a new era in fighting fat, an FDA advisory voted 18-to-4 to recommend the agency approve the Arena Pharmaceutical diet pill, which is known as Lorqess. This marks the second time in three months that an FDA panel has decided the benefits of reducing the growing American waist line outweigh the various risks that have delayed this latest round of fat-fighting drugs from finding their way to medicine cabinets.
In February, an FDA advisory committee voted overwhelmingly in favor of the Qnexa diet pill developed by Vivus. Of course, the recommendations are not a guarantee the FDA will issue approvals. But the back-to-back endorsements – and lopsided votes – suggest the safety concerns that plagued the drugmakers during earlier panel meetings have been sufficiently addressed and increase the odds the FDA will approve the pills.
Unlike the September 2010 advisory panel meeting, Arena was able to overcome concerns about a theoretical risk of an increase in cancer; valvulopathy, which is heart valve damage, and cardiovascular adverse events. Some committee members discussing the possbility of requiring echocardiograms before patients are prescribed Lorqess, given that an increased risk CV events could not be ruled out. Most likely, the FDA would require a post-approval outcomes study.
A related question is whether the FDA would require a REMS, or Risk Evaluation and Mitigation Strategy. A REMS was proposed for Vivus pill, but a key issue with that drug is the risk of birth defects, which does not plague the Arena pill. Nonetheless, the FDA has been consistently cautious in viewing diet pills because these drugs are likely to be widely and, perhaps, inappropriately used, suggesting REMS programs are likely to be employed.
Nonetheless, fighting fat is a key priority for public health agencies. The percentage of obese Americans, which is already a hefty 36 percent, is expected to swell to 42 percent by 2030. And by then, 11 percent could be severely obese, which is deemed to be about 100 or more pounds over a healthy weight, compared with 6 percent two years ago, according to a study released earlier this week in the American Journal of Preventive Medicine (read here).
However, one public health advocate says the FDA bent overbackwards toward this end. Diana Zuckerman, who is president of the National Research Center for Women Families, a nonpartisan, nonprofit think tank, says the FDA’s Center for Drug Evaluation Research “has been under pressure to approve more drugs to reduce obesity. The pressure is from the many groups focused on reducing obesity. Their mantra has been that the risks of obesity are much greater than the risks of these drugs.”
“The consumer and public health advocates, in contrast, point out that the benefits of these drugs are very limited. Study after study show that many patients stop taking the drugs after a few weeks or months, and even those they stay on for six months or more tend to stop taking the drugs as soon as the benefits plateau. Then, they gain the weight back again. In other words, the drugs have the same long-term impact as yo-yo dieting,” she writes in an e-mail.
Lorqess “did not meet the weight loss standards that FDA requires, and has risks of suicidal thoughts, neurological problems and possibly breast cancer. CDER knew their usual Advisory Committee was unlikely to recommend approval, so the agency added more clinicians,” she concludes. “The clinicians almost always want ‘more options’ and voted to recommend approval for this ineffective, possibly dangerous drug.”