Pubdate: Mon, 05 Mar 2001
Source: Forbes Magazine (US)
Copyright: 2001 Forbes Inc.
Contact:  28 West 23rd Street, 11th Floor, New York, NY 10010
Fax: (917) 606-7262
Website: http://www.forbes.com/forbes/current/
Author: Zina Moukheiber

DRUG WARRIOR

When immunologist Philippe Pouletty was a resident at a hospital emergency 
room in Paris in the early 1980s, he was struck by the fact that, although 
20% of patients admitted were drunks or drug addicts, doctors had no 
adequate treatment for them. Occasionally he would quiz drug industry 
executives on the problem: "Tell me which disease has 30 million chronic 
patients worldwide and costs 1% to 3% of the U.S. gross national product."

"No one guessed addiction," Pouletty says. He decided to do something about 
it. In 1994 Pouletty formed his third biotech startup and named it 
DrugAbuse Sciences, basing it in Paris and Los Altos, Calif. and devoting 
it solely to developing treatments for alcohol and drug addiction. 
Pouletty, 42, now has six drugs in the pipeline, two of them in late-stage 
human trials—one for drunks and heroin addicts, the other for cocaine 
abusers. DAS has no revenue yet, paying its 25 scientists from the $30 
million it has raised from ABNAmro, Edmond de Rothschild Asset Management 
and other investors.

But most drug companies continue to shun addiction. Except for pockets of 
research in academia, drug companies have devoted almost no funding to 
searching for cures for drug and alcohol addiction. Most of their efforts 
target the $15 billion market for patches, gums and pills to get smokers 
off nicotine, leaving the rough stuff overlooked. "It falls at the top of 
unmet medical needs," says Peter Suzdak, research chief at Guilford 
Pharmaceuticals, which specializes in drugs for brain disorders such as 
Alzheimer's and Parkinson's.

Drug and alcohol abuse costs the U.S. economy $300 billion in medical bills 
and lost productivity, according to federal government estimates. Some 14 
million Americans are hooked on drugs and booze, outnumbering 8 million 
cancer patients almost 2-to-1 and schizophrenia patients 7-to-1. Eli 
Lilly's schizophrenia drug, Zyprexa, pulled in $2 billion in sales last 
year, yet sales of anti-addiction drugs amount to a mere $170 million a 
year, chiefly from naltrexone, for heroin and alcohol, buprenorphine, for 
heroin, and acamprosate, for alcohol.

Yet the mechanics of addiction are more or less well understood. "We're 
further along in addiction than depression and schizophrenia," says David 
Self, a neuroscientist at the University of Texas Southwestern.

To Pouletty, the industry's apathy recalls its attitude toward depression 
drugs in the 1980s, when marketers believed the market would amount to no 
more than $200 million per year. Prozac's release in 1988 stunned the 
skeptics and ignited a frenzy for feel-better pills; that market now tops 
$10 billion in annual sales.

Treating addiction through medication, though, presents a tougher set of 
challenges. Getting junkies to cooperate with clinical trials can be 
tricky. The dropout rate ranges from 15% to 50%, compared with 3% to 4% for 
cancer and cardiovascular trials. Addiction carries a potent social stigma, 
too. Treating crackheads doesn't quite fit the wholesome image 
pharmaceutical companies want to project.

Most past efforts have been incidental and have been abandoned at the 
earliest sign of failure. In 1996 Guilford came up with a compound that 
successfully blocked cocaine from binding with the brain's dopamine 
transporters, but it didn't stop the cravings. The company ended up 
scrapping its research.

In the same year Abbott Laboratories had hopes that an experimental 
Parkinson's drug, ABT 431, could stabilize levels of dopamine in coke 
addicts. By raising depleted levels of dopamine, a feel-good molecule 
released in moments of pleasure, Abbott hoped to fend off the craving for 
cocaine. But the company struggled with formulations. When it scrapped its 
Parkinson's program, out went the cocaine experiments.

DuPont markets a treatment for alcohol and heroin, naltrexone, which blocks 
the brain receptors involved in producing the highs from those substances, 
but it has been a major disappointment. Patients forget to take their daily 
tablet, so doctors don't widely prescribe it. Total naltrexone sales are a 
mere $30 million, despite the fact that major insurers often cover it.

Pouletty, aiming to overcome those hurdles, is working with both naltrexone 
and Abbott's Parkinson's compound. To get around the problem of addicts 
failing to follow a drug regimen, DrugAbuse Sciences is developing a 
controlled-release version of naltrexone that requires only a monthly 
injection. Naltrel, as it is known, is in the last phase of human trials. 
So far one injection eliminated the highs experienced by a group of 15 
heroin users for six weeks. And the company hopes to improve the absorption 
(and impact) of Abbott's 431 compound by developing it as an inhaler.

DrugAbuse Sciences also is working on a cocaine vaccine, licensed from the 
Scripps Research Institute. Scripps scientists used lab rats to prove that 
the body's immune system can be prompted into destroying cocaine molecules 
before they cross from the blood into the brain. The vaccine is made from 
cocaine that has been chemically rendered inactive and attached to a bulky 
protein extracted from crabs. Pouletty's goal is to begin human trials by 
year-end. A similar vaccine from Cantab Pharmaceuticals in the U.K. is in 
midstage human testing.

Pouletty is pursuing some original research, as well. This year he will 
start enrolling 6,000 alcoholics in seven European countries in an 
ambitiousproject to sequence 150 genes in the brain. By comparing genes of 
alcoholics with those who are not, Pouletty hopes to pinpoint any genetic 
anomalies that may make suitable drug targets.

One blockbuster from Pouletty would likely set off a wave of anti-addiction 
drug development. But even he knows that all the medicine in the world 
can't offer a panacea for addicts. Ultimately they have to choose sobriety 
on their own.

(SIDEBAR)

Kicking The Habit

Only a handful of anti-addiction drugs are slated to come to market soon.

Drug      	Application        Owner                      	Status

Subutex     	Heroin           	Developed           	Waiting for FDA
		addiction          by Reckitt                	approval

Benckiser;			marketed by
				Schering-Plough.

Campral    	Alcohol         	Merck KGaA           	Filing for
		addiction                                    	FDA approval

Naltrel      	Alcohol           	DrugAbuse         	Late-stage clinical
		addiction           Sciences                   	trials

TA-CD    	Cocaine           	Cantab                    	Mid-stage
		addiction      	Pharmaceuticals          	clinical trials
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MAP posted-by: Keith Brilhart