Catalyst focuses on drug to treat addicts

PHARMACEUTICALS

Catalyst Pharmaceuticals in Coral Gables is developing a drug
that could be a major help to addicts who want to quit.

BY JOHN DORSCHNER

Catalyst Pharmaceutical Partners in Coral Gables has a single drug, but it has huge potential: It suppresses dopamine levels in the brain, which could be a major factor in battling cocaine and methamphetamine addiction — and perhaps treat nicotine, alcohol, obesity and gambling problems as well.

Catalyst is a young Coral Gables drug company with a veteran industry chief executive who is betting everything on vigabatrin, an interesting drug with a long history and a problematic side effect.

"Everybody is really excited and pumped," says Chief Executive Patrick J. McEnany of the small team he has assembled.

Catalyst stock started trading publicly in November, generating $21 million its initial public offering. It is about to start clinical trials on 200 to 300 cocaine and meth addicts. Approval by federal regulators could be four years away, if it ever comes.

"Drug development is a risky business. There is no doubt about it," says McEnany.

But much of the toughest work has already been done, by a federal scientist who has been studying the drug for two decades at taxpayer expense. If the drug succeeds, Catalyst could get hundreds of millions in annual revenue, but the firm will have to pay the government no more than $500,000 a year.

What's more, the Food and Drug Administration has put vigabatrin on a fast track for regulatory approval because it provides an unmet medical need for a life-threatening illness.

Vigabatrin was developed in the 1970s by an American company for the treatment of epilepsy. Under the brand name Sabril, it is now sold by a Belgium firm in more than 60 countries, but not the United States.

The problem is that long-time usage of Sabril can lead to irreversible loss of peripheral vision in as many as one-third of the patients who use it.

"That's a very interesting issue," says Stephen Dewey, a senior researcher at the federal government's Brookhaven Laboratory on Long Island, N.Y. "The first report of a visual side effect didn't occur for over a decade," because patients themselves did not notice the problem. It was only when tests were run on them that the side effect became known.

Doctors in Europe and Canada who still prescribe the drug are instructed to have their patients undergo regular vision tests so that they can stop taking the medication before eye deterioration goes too far.

Still, Dewey was fascinated by the drug because it had a crucial relationship with the chemical neurotransmitter dopamine, which increases naturally and temporarily during pleasant experiences such as eating and sexual arousal. Many addictive drugs and other troubling behaviors are linked to dramatically increased dopamine — a euphoric high that the addicts crave.

Vigabatrin's value is that it builds up levels of gamma-aminobutyric acid, or GABA, which suppresses the brain's response to dramatic increases in dopamine.

Starting in the 1980s, Dewey has been looking extensively at vigabatrin in animals, in all sorts of permutations, and some basic tests in humans. "No other drug has been studied this extensively for drug abuse," the scientist says.

In every permutation, the drug seemed to work well. What's more, a regimen for addiction treatment involved a total of about 200 grams of vigabatrin — far below the 1,500 to 2,500-gram levels that were found to cause eye damage in epileptics.

The federal government took out patents for vigabatrin as a treatment for addiction and began looking for a company that would take it through the complex final clinical trials and get it to market.

Meanwhile, McEnany was looking for something to do. A Miami native, he had been chief executive of Royce Laboratories, a South Florida generic drug maker that was bought by Watson Pharmaceuticals in 1997. McEnany worked for Watson a year, but he was "bored to tears," and he left to set up Catalyst Management to look for new opportunities.

His partner in that venture was Hubert Huckel, a physician who had been in the pharmaceutical industry for decades.

In 2002, they approached Brookhaven. At the time, says McEnany, Big Pharma didn't have an interest in the field: It didn't seem like a billion-dollar home run — the next Lipitor or Viagra — because prescription drugs weren't considered a major source of attacking addiction. There were also questions about whether addicts had insurance to pay for the drug.

That's why Catalyst was able to negotiate such a good deal with the government, which wanted to get the drug to market because of the social-economic implications of reducing the number of addicts.

Since then, says McEnany, there have been a flurry of drugs appearing to attack similar behavioral problems. Vivitrol is under development to treat alcohol dependence. Acomplia, already on the market in Europe, blocks receptors that govern food intake and tobacco dependency.

"I think eyes are opening up," says McEnany. Government programs like Medicaid and private insurance are showing heightened interest in paying for the drugs.

Catalyst has had three, small, private placements of capital by "friends and family," for a total of about $5 million. In Mexico, they've done two studies of addicts who went to clinics for treatment. The tests showed promise, and the nine-week regimen revealed no vision side effects.

About 700,000 drug addicts are in therapy in the United States, says McEnany. "That is our market. Clearly, [the patient] has to be in therapy, and he has to want to quit.

Last year, Catalyst approached venture capitalists about a bigger round, but decided the VC crowd wanted too much say in the company's affairs, so they decided for an early IPO.

McEnany did a road show — "55 one-on-one presentations and a dozen lunches and dinners" — but the risky nature of a company trying to develop a single drug did not appeal to many, and the firm dropped its IPO price range from $11-$13 down to $6.

Still, the firm raised $21 million — enough to get them through their clinical trials. The original plan was to focus first on 200 to 300 cocaine addicts, but a few days ago, the firm decided it would be better to do two studies: One of 100 to 150 cocaine addicts and another of 100 to 150 methamphetamine addicts. Meth abuse has been a soaring problem, with governments begging for something that will help.

Lauren Williams, a University of Miami addiction psychiatrist, says vigabatrin shows promise. "Actually, there's a very similar drug also being investigated" — Topamax, already on the market in the United States for epilepsy, which is also known to lower dopamine levels.

Dewey, the lab scientist, says he's studied Topamax along with more than 30 other drugs for addiction-fighting potential. He says Topamax raises GABA levels by 15 to 20 percent, compared with vigabatrin's 1,000 percent, and has undesirable side effects, such as making the patient feel "cognitively impaired."