Contrave: Where Does New Obesity Drug Fit in Armamentarium?

Marlene Busko

October 27, 2014

US physicians treating overweight and obese patients now have four drugs with different mechanisms of action that they can choose to prescribe, to complement diet and exercise.

The latest therapeutic addition is bupropion/naltrexone (Contrave), which was developed by Orexigen Therapeutics and is now marketed by Takeda Pharmaceuticals.

Pharmacies began supplying the drug last week , on October 20, 2014, following its September 10 approval by the US Food and Drug Administration (FDA).

Medscape Medical News asked two physicians in the field how they view the newly expanded market.

"This is a really good time for obesity medicine, in the sense that we now have multiple choices and multiple tools that we can use to help patients lose weight," said Dr Ken Fujioka, director of the Nutrition and Metabolic Research Center, Scripps Clinic, in San Diego, California.

Individuals with 10 to 20 pounds to lose may successfully shed them by diet and exercise alone, and at the other end of the weight spectrum, morbidly obese individuals may be candidates for bariatric surgery.

"But for the average patient, and unfortunately the average American is 20 to 50 pounds overweight or obese," other treatments are needed, he said.

Dr Lee Kaplan, director of the Obesity, Metabolism, and Nutrition Institute, Massachusetts General Hospital, Boston, and chair of the clinical committee of the Obesity Society, agrees that having additional weight-loss tools is important, since "some patients will do better with one drug vs a different drug."

And, as always, clinicians need to balance the potential risk of a particular drug against the potential benefit for an individual patient.

Dr Kaplan calls for greater efforts to develop more obesity-treatment therapies, pointing out that there are about 120 different antihypertensive drugs in 10 different categories, compared with four drugs in four categories for obesity.

But at least the United States is faring better in this regard than Europe. The European Association for the Study of Obesity (EASO) has called attention to the dire lack of obesity drugs in the European Union.

The European Medicines Agency has steadfastly refused to approve any of the newer medications for obesity, citing safety concerns. The only agent available to doctors there is orlistat, an older agent.

Indeed, the EU agency is not the only body concerned about the safety of these agents.

There is considerable debate in the United States too, as has been evidenced by correspondence in JAMA Internal Medicine this year, as reported by Medscape Medical News. And the healthcare informatics company AdverseEvents has just released a comparative safety review of US-approved obesity drug treatments in response to the recent Contrave approval.

Difficult Decision — Which Drug to Use First?

However, many US doctors, backed by the Obesity Society, have argued that obesity drugs are desperately needed to help tackle the epidemic sweeping the nation.

The weight-loss drugs approved in the United States are indicated for use in conjunction with diet and exercise for adults over age 18 with a body mass index (BMI) of 30 higher or those with a BMI of more than 27 and at least one weight-related comorbidity such as hypertension, type 2 diabetes, or dyslipidemia.

Prescription orlistat (Xenical, Genentech) was approved by the FDA in 1999; over-the-counter orlistat (Alli, GlaxoSmithKline) was approved in 2007; and the prescription drugs lorcaserin (Belviq, Eisai) and phentermine/topiramate (Qsymia, Vivus) were approved in 2012.

This was followed by last month's approval of Contrave.

Also awaiting approval for obesity is the injectable GLP-1 agonist already marketed for type 2 diabetes, liraglutide (to be called Saxenda, Novo Nordisk); an FDA advisory panel voted 14 to 1 in favor of approval on September 14.

Choosing the right weight-loss therapy for the right patient is therefore becoming more complex. "It will be a difficult decision — which drug will you use first?" Dr Fujioka said.

And although there are no head-to-head comparisons of the available agents, each drug has unique features that may make one more suitable for some patients but not for others, he notes.

For example, Qsymia was studied in morbidly obese patients with multiple comorbidities and is specifically contraindicated in pregnant women due to increased risk for birth defects in the offspring.

Therefore, "my patient group with Qsymia tends to be older and heavier with more medical problems," he explained.

Meanwhile, Belviq has been studied in overweight white women who didn't have much comorbidity, and it acts to promote satiety. Therefore, "this would be a medication that would be beneficial for somebody who has problems with…eating smaller portions," he observed.

Dr Fujioka said he prescribes Xenical to less than 3% of his patients, but it can be useful for those who are "addicted" to high-fat fast food, who then quickly learn to avoid this food, he pointed out.

Where Does Contrave Fit?

The prescribing information for the newly available Contrave states that the safety of combining it with other weight-loss products and its effect on cardiovascular outcomes are unknown.

It also carries boxed warnings stating that the drug has not been tested in a pediatric population and may cause suicidal thoughts and behaviors in children and adolescents (for which it is not approved) and in young adults age 18 to 24.

The FDA therefore granted the Contrave approval with the proviso that the company conduct postmarketing studies of drug-drug interactions, cardiovascular effects, and safety/efficacy in children.

However, most obese patients who come for weight-loss treatment are in their mid-40s, and studies suggest this drug could be helpful in the subset of patients with food cravings, Dr Fujioka noted.

Takeda will initially provide patients who are prescribed Contrave (and do not have any Medicare, Medicaid, or other government insurance coverage) free access to the "Scale Down" support program, in which they receive a special scale that is wirelessly connected to the Internet, weigh themselves daily, and get personalized text messages about healthy habits.

Dr Fujioka has served as a consultant for Orexigen Therapeutics, Allergan, Novo Nordisk, Enteromedics, Zafgen, NPS Pharmaceuticals, Arena Pharmaceuticals, and Jenny Craig. He has served as a speaker for Abbott Laboratories and Merck and has received research grants from Orexigen Therapeutics, Novo Nordisk, Enteromedics, Amylin Pharmaceuticals, NPS Pharmaceuticals, Arena Pharmaceuticals, Jenny Craig, and Weight Watchers. Dr Kaplan serves as a scientific consultant to Takeda, Vivus, Eisai, Novo Nordisk, GI Dynamics, and Johnson & Johnson.

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