As new weight-loss drugs hit market, no single one to fatten up category
NEW YORK —As many as eight pharmaceutical solutions to a condition that affects some one-third of Americans—a condition that plays a significant role in the development of diabetes, heart disease and arthritis—are expected to reach the market in the next few years.
The condition is obesity. And while no one pharmaceutical weight-loss solution is expected to reach blockbuster sales of more than $1 billion, collectively, the market may be as large as $3 billion by 2016, according to a Wolters Kluwer Pharma Solutions analysis of the drugs in development.
The highest revenue generator in Wolters Kluwer’s model is Arena Pharmaceutical’s lorcaserin, which is expected to reach peak worldwide sales of $850 million if approved.
The four drugs closest to filing a new-drug application are Arena’s lorcaserin, currently being tested in phase-3 trials; Orexigen’s Contrave, a fixed-dose combination of sustained-release naltrexone and bupropion in a single, trilayer tablet with an NDA planned for first half 2010; Vivus’ Qnexa, a combination of low-dose phentermine and topiramate, which currently is part of three phase-3 studies for obesity and a phase-2 study for diabetes; and Novo Nordisk’s liraglutide, a long-acting, stable analogue of the natural hormone glucagon-like peptide-1 (glp-1), which currently is in phase 3 for obesity, and under regulatory review in the United States, Europe and Japan for diabetes.
Of the prescription drugs that currently are available in the United States to treat obesity, only two—Abbott’s Meridia (sibutramine) and Roche’s Xenical (orlistat)—are approved for long-term use. And in June 2008, Roche partnered with GlaxoSmithKline on the launch of a nonprescription orlistat 60 mg under the brand name Alli.
While Meridia has the ability to control appetite, offering an average weight loss of4.3% over one year, it can lead to hypertension and increased heart rate. Xenical leads to weight reduction through the inhibition of fat absorption in the gastrointestinal tract. Despite leading to an average weight loss of 2.9% over one year, approximately 20% to 30% of patients taking the drug experienced embarrassing and unpleasant gastrointestinal side effects, including fecal incontinence and urgency.
Between efficacy of less than 5% weight loss and the fact that neither is reimbursed by third-party payers, neither obesity drug really has taken off in sales.
There actually are a total of three factors that will drive widespread adoption of antiobesity agents, Wolters Kluwer Pharma Solutions analyst Claudia Wiatr told Drug Store News—safety, efficacy and reimbursement. Cost and reimbursement perhaps are the most critical to the ultimate adoption of any antiobesity medication, especially as current antiobesity drugs generally are not reimbursed by third party payers in the United States, and many patients are unwilling to pay the more than $100 per month, Wiatr said.
Promising developmental obesity agents| DRUG NAME | DEVELOPER | PHASE | ESTIMATED U.S. APPROVAL | PROJECTED 2016 U.S. REVENUE* |
| lorcaserin | Arena Pharmaceuticals | 3 | March 2011 | $713 |
| Contrave (naltrexone/buproprion) | Orexigen Therapeutics | 3 | March 2011 | 546 |
| Qnexa (phentermine/topiramate) | Vivus | 3 | August 2011 | 437 |
| liraglutide | Novo Nordisk | 3 | March 2012 | 517 |
| empatic | Orexigen Therapeutics | 2 | March 2013 | 243 |
| tesofensine | NeuroSearch | 2 | March 2013 | 267 |
| pramlintide/metreleptin | Amylin | 2 | August 2013 | 291 |
| cetilistat | Takeda/Alizyme | 2 | March 2014 | 12 |
| TOTAL PROJECTED REVENUE | $3,026 | |||
The first hurdle that these new obesity drugs need to clear, though, is safety, Wiatr said. “The environment at the [Food and Drug Administration] is very risk-averse,” she said. And the agency likely is to be especially cautious with obesity drugs in light of the psychiatric side effects associated with the class of weight-loss drugs called cannabinoid-1 receptor blockers, such as Acomplia (rimonabant), an obesity remedy that has never been approved for use in the United States and was removed from the European Union market.
The greatest hurdle for any of these new weight-loss drugs, however, is reimbursement—the higher the out-of-pocket expenses are to the end-consumer, the less trial that is likely to ensue. “For a patient to pay $100 per month out-of-pocket for something that only gives 5% weight loss—a lot of patients don’t want to do that,” Wiatr said. At the same time, no drug is going to be reimbursed if it only offers 5% weight loss on average, which is the minimum amount of weight loss that has to occur in clinical trials to prove efficacy to the FDA. “In order for a drug to have commercial success, you need weight loss and efficacy on the order of at least 15%,” she said. “That gives you the greatest chance at optimal reimbursement.” However, only one drug—the pramlintide/metrelptin combination—approaches some 12.7% of weight-loss efficacy, Wiatr added, which is partly the reason no one obesity drug will become a blockbuster.
However, a second aspect of reimbursement is being able to obtain a label for an additional application that already is reimbursable, Wiatr said. For example, Qnexa and liraglutide also are being studied for diabetes, thereby increasing their chances for reimbursement as an obesity remedy.