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Ingenuity vs. obesity

Companies testing drugs, devices aimed at helping patients control waistlines

By Carolyn Y. Johnson
Globe Staff / March 7, 2011

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The battle against the obesity epidemic has been punctuated by pharmaceutical failures, but that isn’t stopping local device and biotechnology companies from jumping into the fat-fighting fray.

With strategies that span the gamut — from superabsorbent particles that swell in the stomach to help people feel full to drugs that target fat production or energy balance — companies are working on strategies that could one day turn into treatments for obesity or type 2 diabetes.

The demand is growing. About two-thirds of adults in the US are obese or overweight, according to federal health data, and a growing number of people worldwide struggle with bulging waistlines that increase risk for type 2 diabetes or cardiovascular disease.

But in the past year alone, federal regulators have rejected a handful of drugs because of safety concerns. That has led local companies to try a number of different strategies.

Some are focused on physical devices that could avoid many of the side effects of drug interventions. Others are developing drugs that act on new biological targets, and at least one company is doing preclinical testing in obese primates, as a better model of how effective and safe a drug will be in people.

“We have fewer drugs than we’ve had at any time; not only have there been drugs or combinations that were not approved, but we also had one taken away over the past year,’’ said Dr. Lee Kaplan, director of the Massachusetts General Hospital Weight Center, and an adviser to several companies. “We’re really where we were around 1997, and even before that, in terms of our effective therapy.’’

The companies are in various stages of development, and it is unclear which therapies will make it to market.

One of the oddest ideas — a thin sleeve that lines the upper portion of the small intestine — is one of the furthest along. The EndoBarrier received approval in Europe late last year to treat type 2 diabetes and obesity.

Stuart Randle, chief executive of GI Dynamics, the Lexington company that makes the device, said the goal is to emulate the effects of bariatric surgery with a temporary, noninvasive intervention. The device is placed in the body through a tube inserted in the mouth.

Food passes through the EndoBarrier, coming into contact with the small intestine about two feet farther than it usually would, delaying digestion. Researchers believe it changes the hormone signals that influence hunger and the body’s energy use. In a yearlong study of 13 obese patients with type 2 diabetes, the device improved blood glucose levels and caused weight loss. In another study, 24 obese patients experienced more than 20 percent weight loss over a year. The main side effects, Randle said, were nausea and vomiting in the first few weeks.

The company expects to start a clinical trial in the United States next year.

A similarly offbeat obesity treatment is being developed by Gelesis, a Boston company that was looking for a safe, noninvasive way to emulate approaches that reduce stomach volume.

The company has begun testing Attiva: a capsule packed with superabsorbent particles made up of food components. When mixed with water, the capsule dissolves and particles expand into larger gelatinous particles that fill the stomach and slow down its emptying, as well as digestion.

In a human trial, Attiva was tested in 95 people for three days, and people reported feeling full for longer and less hungry at the next meal. Studies over a longer time period will be necessary to show whether the device causes weight loss.

Other companies are focused on drugs.

Rhythm Pharmaceuticals of Boston, for example, tested its experimental obesity and diabetes drug in an eight-week study of obese primates. The company reported the animals experienced 13 percent weight loss, without adverse side effects.

The company plans to start its first studies in humans this year.

Zafgen, a Cambridge company, is testing an injectable drug, ZGN-433, that inhibits an enzyme called MetAP2. The drug has a range of effects, including reducing the activity of genes in the liver that are involved in fat production and burning existing fat.

In results presented at a conference in January, the company reported results from a trial, including improvements in measurements of cardiovascular disease risk and about two pounds of weight loss a week over 26 days.

At an earlier stage is Energesis Pharmaceuticals, a Cambridge company that is working to activate or increase the amount of brown fat, a type of fat that burns energy.

It is impossible to know which, if any, of these companies will succeed, but Kaplan points out that intense efforts are needed to combat obesity. Right now, he said, the main tools are lifestyle interventions such as diet and exercise plans, or — at the other end of the spectrum — surgery.

“What we’ve got are the two extremes and nothing in between,’’ Kaplan said. “We have to take what we know about the mechanisms underlying obesity — we know a lot — and develop therapies based on knowledge.’’

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

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