Orexigen obesity drug shows added benefits: studies

Orexigen obesity drug shows added benefits: studies
By Bill Berkrot

NEW YORK (Reuters) - Nearly half of patients who completed 56 weeks of treatment with Orexigen Therapeutics Inc's experimental obesity treatment, Contrave, lost at least 10 percent of their weight in a late-stage study and the drug also appeared to help cholesterol and blood sugar levels.

The drug demonstrated an even greater improvement in non- weight loss measures in patients considered to be at high risk of heart disease, according to data released on Saturday.

Orexigen released top-line data in July from a trio of Phase III trials showing Contrave met its primary goal of at least 5 percent weight loss compared with a placebo.

That data included all patients who began the studies, even those who discontinued the medicine at any point. The data presented Saturday included only those who completed 56 weeks of treatment, which the company called "a more clinically relevant number."

Orexigen also released data that looked at several secondary measures, such as impact on waist circumference, blood lipids and a marker for inflammation, as well as blood sugar levels in a separate trial of obese diabetics.

"We're very encouraged that all those things are going in the right direction," Dennis Kim, Orexigen's head of medical affairs who presented the new data at the Obesity Society scientific meeting in Washington, said in an interview.

Contrave is a pill that combines the antidepressant Wellbutrin, known generically as bupropion, with a sustained- release version of naltrexone, an opioid blocker used to treat alcoholism and other addictions.

New obesity treatments are needed for what has become a public health epidemic as obesity is a leading cause of diabetes, heart disease and many other serious medical problems, and the condition is rising at alarming rates.

The top-line data in July showed 48 percent of obese patients lost at least 5 percent of their body weight in one trial and 56.3 percent in a second study, compared with 16.4 percent and 17.1 percent on placebo.

Those differences are considered robust enough for likely FDA approval and the company said it was on track to apply for U.S. approval in the first half of next year.

But when looking only at patients who completed the 56-week study, the Contrave numbers jump to 61.8 percent and 75.8 percent compared with 23.1 percent and 21.7 percent on placebo.

In addition, 48.2 percent of Contrave patients lost at least 10 percent body weight and 23 percent dropped an impressive 15 percent of their weight in one of the studies.

In the other Phase III trial, 34.5 percent lost at least 10 percent on Contrave and 17.2 percent achieved 15 percent weight loss -- all significantly better than the placebo group, which topped out at 3.4 percent losing 15 percent of body weight and 10.7 percent who dropped 10 percent.

"These numbers demonstrate some really compelling efficacy results that I think patients and prescribers will be impressed by," Kim said.

The data also demonstrated impressive impacts on blood lipids and other measures in those patients in the study considered to be at high cardiovascular risk.

In that population, triglycerides went down 66.3 milligrams/deciliter and 51.2 mg/dl on Contrave.

"Those drops in triglycerides actually is in the ballpark of what you would expect to see from a lipid lowering drug that's on the market today," Kim said, referring to Abbott Laboratories' blockbuster triglyceride lowerer TriCor.

Levels of good HDL cholesterol rose 5 mg/dl and 6.2 mg/dl among Contrave at risk patients -- similar to what one would expect from niacin, which is approved to raise HDL.

High risk Contrave patients also had significant drops waist circumference and c-reactive protein -- an indicator of arterial inflammation associated with heart disease -- and small drops in bad LDL cholesterol, according to the data.

Blood sugar levels from the study of diabetics was also more impressive than originally thought when looking at just patients who began the trial with A1c levels of greater than 8 percent. American Diabetes Association guidelines call for an A1c level of 7 percent or less.

Among those patients, Contrave led to a highly statistically significant mean A1c reduction of 1.1 percent.

"That is very impressive and outdoes a lot of diabetes drugs that are approved today," Kim said. "And you get big weight loss on top of it."
(Reporting by Bill Berkrot; editing by Andre Grenon)