By Patricia Anstett
Free Press Medical Writer
With the fate of a top-selling diabetes drug mired in controversy, Kalamazoo scientists are working to develop the next generation of medicines that improve diabetic care without serious side effects.
Metabolic Solutions Development is a start-up Michigan company with two drugs in its pipeline to improve blood glucose and insulin measurements without causing the weight gain, fluid retention and heart problems associated with Avandia.
The federal Food and Drug Administration is weighing a July 14 decision by an advisory panel to restrict sales of Avandia or require stronger warning labels on the drug.
Avandia, which is used by about 23 million Americans, is at the center of hundreds of lawsuits filed against GlaxoSmithKline, its manufacturer, by patients claiming unwanted side effects from the drug. The company is working closely with the FDA to monitor the drug and its side effects, according to a statement on its Web site.
The two drugs from Metabolic Solutions to treat type 2, or adult-onset, diabetes await several more years of tests and won't be ready to fill any immediate void if the FDA restricts Avandia's drug sales or patients concerned about side effects switch to other medicines.
But preliminary studies have found that both Metabolic Solutions medicines improve insulin sensitivity and lower cholesterol and blood glucose levels without causing weight gain or serious side effects, the company says.
"The discussion around Avandia has proven that the marketplace wants diabetes drugs that do more than simply lower blood glucose," said Jerry Colca, chief scientific officer of the company he cofounded in 2005.
Diabetes is a major drug company target and has been for years. An estimated 17.9 million Americans are diagnosed with diabetes and another 6.3 million are unaware they have the problem, and the numbers are growing with America's obesity epidemic.
Most drug companies went in a different direction finding cellular targets for their drugs, said Robert Beardsley, CEO at Metabolic Solutions. He compares the cell paths chosen by other pharmaceutical companies to the wrong turn that a float driven by fraternity brothers following a band took into an alley in the movie "Animal House."
"Just like 'Animal House,' they went down a blind alley," he said.
Metabolic Solutions' drugs target the powerhouse, or energy-producing, part of the cell, the mitochondria, whereas other drugs aim at the cell's nucleus, Colca said.
The difference is that Metabolic Solutions' drugs switch on a path that tells the cell to burn energy from food immediately, rather than storing it as fat for later use, he said. Beardsley said the difference is "like eating a hamburger and wanting the fat to go to your thighs rather than making fuel that helps you feel invigorated."
Colca and Rolf Kletzien began Metabolic Solutions after long careers in diabetes research with several Michigan drug companies, including Pfizer and the onetime giant Upjohn. They used retirement income to start the company, and a bedroom at Colca's Kalamazoo condominium served as an office for their first two years.
And that's where the Michigan tie comes in.
In a state that once housed several companies that eventually merged into the giant Pfizer pharmaceutical company, there were lots of talented scientists with experience making and distributing drugs, Beardsley said. "This is a story that only could happen in Michigan," Beardsley likes to say.
Instead of building a company that housed all the components of drug research, development and distribution, Metabolic Solutions chose to parcel out its work to more than a dozen Michigan contractors with expertise in the field, from lawyers specializing in intellectual property rights to companies with know-how in toxicology and drug development.
Help also came from a $2.5-million grant from the Michigan Economic Development Corp., which allowed the company to set up a laboratory and hire a director to run it, along with $1.6 million in two federal grants that aid small companies in development stages.
The company also raised $25 million, mostly from Michigan investors to date, to develop the company and help it conduct its early studies. It is working to raise another $20 million to $30 million to begin other clinical studies testing the drugs in humans.
The likelihood is strong that the company will team up with a larger drug development firm to conduct large human studies of the drugs, Beardsley said.
"Developing a diabetes drug is very expensive," involving possibly hundreds of millions of dollars eventually, Beardsley said. With drug development and research costs totaling as much as $300 million to $500 million for a new medicine, Beardsley said that the company will need a partner someday.
It also is hoping that some of the same drug targets its compounds select will pay off someday in treatments for other diseases.
"Many of the diseases of aging involve the loss of mitochondria," Colca said. "It's a mechanism we are touching that is very important" with some types of cancer, heart disease and neurological problems, he said.
Copyright 2010 Detroit Free Press reprinted with permission.
Date: July 25, 2010
Source: Detroit Free Press