More info on wt loss drug

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An FDA advisory committee has voted 13-7 that the modest weight-loss

benefits of an investigational combination of naltrexone and bupropion

(Contrave) outweigh the drug's blood pressure risk.

The bupropion naltrexone combo is the last in a trio of new weight-loss

drugs that went before FDA panels this year, striving to be the latest

treatment in the dwindling field of medications to fight obesity. The

previous two drugs, phentermine/topiramate (Qnexa) and lorcaserin

hydrochloride (Lorqess) were both rejected by the FDA after they fared

poorly at advisory committee meetings.

But Tuesday's advisory committee ended very differently than the previous

two.

Bupropion/naltrexone appeared to offer fewer side effects than the previous

two drugs, although it also doesn't appear to work as well at helping obese

patients lose weight.

The FDA will make an approval decision by Jan. 31. The agency does not have

to follow the advice of its advisory committees, but it often does.

Orexigen, the company that makes naltrexone/bupropion in partnership with

Takeda, is seeking approval for treatment of obesity and weight management

in patients with a body mass index of 30 or above, or 27 or above and with

one or more risk factors (e.g., diabetes, dyslipidemia, or hypertension).

Contrave combines an antidepressant and an anti-addiction drug, both of

which have been used individually for 20 years -- naltrexone for opioid

addiction and alcohol dependence and bupropion for depression and smoking

cessation. However, little is known about combining the drugs for weight

managment.

The Endocrine and Metabolic Drugs Advisory Committee reviewed results from

Orexigen's four placebo-controlled, one-year, phase III clinical trials,

which enrolled 3,200 obese patients with at least one comorbid condition,

including diabetes and depression.

In all four trials, patients on the naltrexone/bupropion combination lost

more weight than those in the placebo group (*P*<0.001), and more than 30%

lost at least 5% of their body weight, which is one standard by which the

FDA judges efficacy of weight-loss drugs.

In a pooled analysis, naltrexone/bupropion patients lost an average of 4.2%

more weight than the placebo group (ranging from 3.3% to 4.8%). That falls

short of the other FDA standard that after one year, the difference in mean

weight loss between the active and control groups should be at least 5%.

In one trial where patients taking naltrexone/bupropion were compared with

those undergoing a lifestyle modification program, the difference between

the groups was even smaller, suggesting that diet and exercise can achieve

similar results as naltrexone/bupropion.

" As far as efficacy goes, I think they made it by the hair of their chinny

chin chin, " said Coffin, the panel's patient representative.

In the FDA's assessment of the drug released last week, reviewers expressed

concerns over several side effects -- a potential increased risk for

dizziness, nausea, seizures, and high blood pressure among patients taking

naltrexone/bupropion.

However, the panel was mostly just concerned with one side effect: The

drug's effect on blood pressure.

In the trials, patients taking naltrexone/bupropion were more likely to have

an increase in blood pressure and heart rate than placebo patients, an

effect that was most pronounced during the first eight weeks of treatment.

However, patients taking naltrexone/bupropion who lost at least 5% of their

body weight achieved lower blood pressure and heart rate compared with those

who lost less weight. But the most impressive improvements in blood pressure

and weight loss were seen among patients taking placebo who achieved more

than a 5% weight loss, suggesting diet and exercise is the best option for

obese patients to lower their blood pressure.

Panelists were concerned that a drug that is supposed to reduce obesity --

and hopefully other comorbidities along with it -- actually raised blood

pressure instead.

" This is my biggest concern, " said Lamont Weide, MD, PhD, chief of diabetes

and endocrinology at Truman Medical Centers Diabetes Center in Kansas City,

Mo. " That we are blunting all the good effects that we should see with

weight loss. "

The FDA reviewers concluded there wasn't enough data on the cardiovascular

risks of the drug. The panel seemed to agree, but voted 11-8, with two

panelists abstaining, that the company could submit new data after approval

to show that the drug doesn't present major heart risks.

The panel's one neurologist, Rogawski, MD, PhD, said he thought the

panel downplayed the drug's seizure risk.

Two patients in the clinical trials experienced seizures after going on

naltrexone/bupropion; no participants in the placebo group had seizures.

About one in 1,000 patients who take the drug would be expected to have a

seizure, the panelists said.

" They occur only in one out of 1,000, but still, the consequences of having

a seizure could be catastrophic, " said Rogawski, who ended up voting in

favor of the drug.

There is currently just one anti-obesity drug on the market: Orlistat

(Xenical, Alli), after Abbott, the maker of another drug sibutramine

(Meridia) voluntarily agreed to remove it from the U.S. market in October

because of increased risk of stroke and MI.

Several physicians and other healthcare professionals contacted by *MedPage

Today/ABC News* were pleased with the panel's decision and said that doctors

badly need a new drug to help patients battle obesity.

" It is nice to have a medication that can help those who are watching their

diet and boosting activity lose the weight that thus far has been a slow

process, " said dietitian Connie Diekman, director of University Nutrition


at Washington University in St Louis. " This is one more option in the tool

chest to deal with the obesity issue. "

" Finally! " said F. Kushner, MD, professor of Medicine at Northwestern

University Feinberg School of Medicine. " I fully endorse the panel's vote.

The key will be to educate physicians on how to best prescribe the

medication -- identify patients who will benefit from the medication and to

accompany it with lifestyle and behavioral recommendations. "

L. Doering, a pharmacy professor at the University of Florida, said he

doesn't " doubt for a minute that this drug will be wildly successful, at

least at first, " adding, " Time will ultimately tell if it is a good drug or

not. In the meantime, I'm going to let somebody else be the first to take

it. "

LINK <http://www.medpagetoday.com/PrimaryCare/Obesity/23793>

--

Ortiz, MS, RD

*The FRUGAL Dietitian* <http://www.thefrugaldietitian.com>

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