By Kari Huus
Updated: 12:54 p.m. PT Nov 1, 2006
A drug cocktail that backers say is the first effective treatment for methamphetamine and cocaine addiction is dividing substance abuse experts into two hostile camps — those who say they have seen it work wonders and those who say it has been rushed to market without any scientific testing.
The strident debate over the "Prometa protocol," manufactured by the Hythiam Corp., is complicated by the checkered Wall Street career of the company's CEO, Terren Peizer, who previously championed an anti-AIDS drug that has yet to make it to market.
Hythiam, which is based in Los Angeles, launched Prometa in 2003 in private clinics, where meth and cocaine addicts, as well as alcohol abusers, pay $12,000 to $15,000 for a one-month outpatient treatment.
Now the company is aggressively pushing Prometa for the mass market, and asking governments and insurers to foot the bill. Already, four county and municipal programs have launched pilot programs and are offering powerful testimonials for the treatment.
The company has a huge receptive potential customer base in health and law enforcement officials in countless small communities that have been broadsided by the costly and seemingly intractable meth and "crack" cocaine epidemics. And it has big ambitions in this grim landscape.
“We believe strongly that one day Prometa will be a standard of care, and should be available to everyone,” Peizer said.
But critics note that the field of addiction treatment is littered with "miracle cures" that ultimately failed or, in a few cases, caused harm to test subjects. And they warn that Prometa has never been subjected to double-blind, placebo-controlled testing — the gold standard for determining whether therapies are safe and effective.
‘It preys on ... desperate patients’
“The marketing is way ahead of the science,” said Lori Karan, a physician-researcher at the Drug Dependence Research Laboratory at the University of California San Francisco. “It preys on the needs of desperate patients, sets unreasonable hopes and expectations and takes advantage of scarce economic resources.”
"What’s being touted here is what people have always wanted for addiction ... something dramatic that is going to fix their brain," agreed Peter Banys, director of substance abuse programs at the VA Medical Center in San Francisco. "I would never recommend that someone spend $15,000 on this with the current state of data (and) I think it’s improper to spend public money on this product at this time."
Prometa has made its way to consumers quickly because of an exception in FDA regulations that allows physicians to prescribe drugs “off-label” — that is, for purposes other than the one for which they were originally approved. For example, Botox, best known as a wrinkle eraser, originally was approved as a treatment for an eye muscle problem but is used off-label to treat migraine headaches.
However, Hythiam is exploring new territory by grouping three FDA-approved drugs for off-label purposes in Prometa. The company doesn't own or produce the three drugs — flumazanil, gabapentin and hydroxyzine — but claims ownership of the process by which they are delivered into a patient's system along with nutritional supplements. It licenses the protocol to individual doctors and clinics, grants franchise rights and administers the treatment at its Prometa centers.
The company, which is seeking a U.S. patent on its “proprietary dosing algorithm,” is secretive about the specific details of the treatment. But it broadly describes it as a process in which patients receive about one hour of intravenous infusion for three straight days, followed by about a month of oral medications and nutritional supplements. Near the end of the month the patient returns for two more IV infusions. The formulation varies, depending on whether it is being used to treat meth, cocaine or alcohol dependency.
Hythiam's doctors aren't sure how Prometa works, but they hypothesize that it repairs the damage to neurotransmitters in the gamma-aminobutyric acid (GABA) receptor complex — the part of the brain that inhibits or calms — caused by extended drug and alcohol abuse. The effect, they believe, is to halt cravings for the drug and allow addicts to think clearly enough to concentrate on changing their lifestyles.
“It resets the receptors and they stay reset,” Matthew Torrington, medical director of the flagship Prometa Center in Los Angeles, told a group of Washington state and local legislators at a recent presentation. By quelling the cravings, he said, "It intensifies the prowess of psychosocial treatment."
Try it now, prove it later
Hythiam is now conducting double-blind studies at UCLA and the University of South Carolina in an effort to establish the efficacy of Prometa and rule out the “placebo effect,” where patients who believe they are receiving a treatment for a medical condition show improvement even when they are given an inert substance.
But those results may not be final until 2008, and the company argues that the results of its field trials are so compelling that use of Prometa should not wait.
“Counties don’t care about double-blind placebo-controlled data," said Peizer. “What’s interesting about Prometa is that out in the field — in the counties, justice systems, private centers — the clinical relevance is being shown daily."
Already, according to Hythiam, more than 1,000 people have undergone treatment with Prometa, with providers reporting unheard of abstinence rates of between 60 percent and 80 percent. Thousands more will receive the treatment in the next year in private settings alone, it says.
The company also is making inroads in the government sector.
Fulton County, Ga., which has a cocaine epidemic and an emerging meth problem, announced in October that it was launching a Prometa pilot program for its parole and probation programs in an effort to curb high recidivism rates.
That comes on the heels of a pilot programs in Pierce County, Wash., and Gary, Ind., where local officials said they saw such dramatic results in meth and cocaine addicts that they are seeking to make Prometa a standard offering. Idaho and Maricopa County, Ariz., also are considering testing the Prometa regimen.
The company is pressing its case on two fronts. Hythiam’s senior officers are talking to investors in U.S. financial centers while doctors employed by the company shop Prometa at anti-drug conferences in meth-blighted areas.
“We are in constant dialogue with providers to government and state agencies and third-party payers and we expect to land initial licensing relationships that will contribute to our 2007 revenues,” Peizer said in the company’s second quarter conference call in August. “Keep in mind, each 400 treatments at the government rate of $2,500 will result in $1 million in revenue. At these levels, even initial volumes can accrue quite rapidly.”
A message from beyond the grave
The company also triggered a controversy early this year with an ad campaign that appeared to be directed at the public at large. Billboards and television and radio ads referred to "Saturday Night Live" comic Chris Farley, who died of an overdose of cocaine and morphine in 1997, and highlighted the Prometa label under the slogan, “The problem is physical, the solution is medical.”
Media reports at the time focused mainly on whether or not it was in poor taste to use Farley's image for a posthumous endorsement.
In addiction treatment circles, it was the direct appeal to consumers that raised eyebrows, since FDA rules do not allow off-label drug uses to be advertised.
Peizer dismisses the criticism from both quarters.
“The Chris Farley campaign was not about advertising, it was about creating awareness," he said. "We only did it to create awareness of the disease.”
Responding to a query from MSNBC.com, a press officer said the FDA was not prepared to comment on whether the ads violated its regulations "without the agency looking further into this."
The spark that led to the creation of Prometa came from a Spanish addiction researcher, Juan Jose Legarda, who in 2003 sold his drug-based approach to Peizer's new company, Hythiam. Peizer quickly gained access to investment capital by gaining listing on the Nasdaq stock exchange through a reverse-merger with a shell company.
The financial maneuver was nothing new for Peizer, who first became known in the investment world as a junk-bond salesman working for Michael Milken in the 1980s. Peizer was compelled to testify in the sentencing phase of Milken's securities fraud trial, and was granted immunity from prosecution.
Also in the early 1990s, he invested in a company called Urethane Technologies, which made extravagant claims about a no-flat tire it was developing for the vast bicycle market in China. Peizer prospered — reportedly earning some $6 million when he sold his shares in 1993 — but the company never delivered and wobbled into bankruptcy in 1997.
A more-celebrated deal came in 2000, when he bought 10 percent of tiny Seattle-based Tera Computer and then orchestrated that company's purchase of Cray Research, the business unit of the bankrupt supercomputer giant. Afterward, the Seattle company changed its name to Cray Inc., and has has parlayed its famous name and computing strengths into profit.
Peizer served briefly as chairman of the board, but left the company in December 2000 when he couldn't get a timely security clearance required because of the firm's classified government work. He remains a large stockholder.
One executive involved in a deal with Peizer described him as an eloquent vagabond.
“He’s smooth and a bit of a showman. He can talk to different folks at different levels,” said the executive, who spoke on condition of anonymity. “He’ll peddle a story, and then he’ll move on.”
AIDS drug flops
Peizer's first foray into healthcare came in the late 1990s, when he invested in Hollis-Eden Pharmaceuticals and got the biotech startup listed on the Nasdaq through a reverse merger. The company's shares soared on hopes for its AIDS-fighting compound Immunitin, despite scant clinical research.
''This is a once in a lifetime opportunity for me. We have something special,'' he told the New York Times in February 1998, referring to Immunitin.
Peizer abruptly left the company in 1999, and Immunitin is still in the research phase.
Peizer sounded a similar note in describing his excitement over the Prometa protocol, telling MSNBC.com that bringing it to market would be the most important thing he had done in his career, even if the company never becomes profitable.
Peizer owns 35 percent of Hythiam, now capitalized at $340 million. Shares are up more than 60 percent in the last three months.
Using drugs to fight drug dependence
Most addiction specialists agree that medical intervention can help treat drug dependence, and several drugs have won FDA approval for treating addiction, though none for stimulants like methamphetamine and cocaine.
B uprenorphine (sold as Suboxone or Subutex) was approved to alleviate withdrawal symptoms in heroin recovery, and it is used for sustaining abstinence. And Naltrexone (brand-name Vivitrol), is approved for use in relapse prevention for heroin and alcohol addictions.
But these drugs went through decades of rigorous testing and tens of millions of dollars before being cleared by FDA and marketed to the public, notes Richard Rawson, professor of psychiatry at UCLA and an outspoken critic of Prometa.
“(Hythiam is) trying to have it both ways,” he said. “They’re trying to say (Prometa) shouldn’t require testing because we’re using these (FDA approved) medicines off label. ... But they can’t say they’ve tested it … to demonstrate that it is a safe of effective procedure.”
His arguments don't sway converts to Prometa, who say the pilot results, although not scientific, cannot be ignored because they are so striking and because counseling has had such poor results among meth users.
Among them is Terree Schmidt-Whelan, director of the Pierce County Alliance, a non-profit treatment center in Tacoma, Wash. Pierce County has one of the highest rates of methamphetamine addiction in the country and all the crime, domestic violence, child neglect and other tragedy associated with meth use.
After being approached by Hythiam, her agency started a pilot program in March with 40 addicts she describes as "the worst of the worst," mostly hard-core meth users.
The results? "Phenomenal," she said.
"I've been in this field for 30 years, and to see people change their lives in a week, and so dramatically, it’s just wonderful," she says.
Pierce County offered the experimental treatment through its family and felony drug courts, which allow those who successfully complete a drug or alcohol treatment program to have their penalties reduced or regain custody of children placed in foster homes.
Schmidt-Whelan says many of the subjects who took part in the trial had failed repeatedly in drug court — missing therapy sessions, or showing positive urinalysis — until they received the Prometa protocol.
The week after their initial infusions, she said she saw a stunning change in their demeanors.
"They would arrive at the door looking completely different than the week before. It was like they had looked in the mirror for the first time in years," she said. "They had shaved, done their hair, stood taller."
She said 37 of the original 40 subjects are now quickly progressing through the drug court program. Of more than 700 urinalysis tests on the group, only 12 have come back positive.
"All (subjects) report an increased ability to focus on the treatment rather than focusing on getting high," said Schmidt-Whelan. "That is huge. It allows people to go out and find jobs, focus on what the therapist has to say, and to focus on the issues that led them to drugs in the first place."
One of those finding a new way to live is 26-year old Suzanne Younker, a three-year meth user who had a $100-to-$200-a-day habit before the Prometa program. Now, after more than six months without drugs, she has a job and is working to gain custody of her son, year-old Kingston.
“You’d have thought that would be motivation enough,” she said, recalling how Kingston was taken from her at birth in the hospital after they both tested positive for meth.
Loss of child strengthened drug's hold
Instead, she sank deeper into the drug’s thrall, getting high every day for about three months until she was arrested, holed up in a hotel room with her two pit bulls.
It wasn't until after Prometa that she could think about something other than her next fix: “I had a maternal instinct that I should have had before,” she said.
Another convert is Harold Urschel, a psychiatrist at Research Across America, a Dallas-based company that runs studies on new therapies.
Urschel gave Prometa to 50 chronic methamphetamine addicts — again, with no control for placebo effect — in a 12-week trial that ended in April. He reports that overall meth usage plummeted for the duration of the study. Thirty-one of the subjects completed the 12-week program.
"I was amazed," he said. “That’s nothing like what I see in clinical practice. We’re talking about getting chronic meth users who had tried to stop numerous times, and the longest they could be sober was 2-3 days, many just one.”
He plans to recommend it to all his patients.
“The scientists who are naysayers have a right to their opinion. But if you’re in the trenches out there … it’s a no-brainer.”
Despite such accolades, the National Institute on Drug Abuse does not agree with Hythiam's marketing-first approach.
"If we had a vote in this, and we don’t, we would say they shouldn’t be doing this," said Frank Vocci, the head of pharmacology at the NIDA, a branch of the National Institutes of Health."We want evidence-based procedures and medicine to be practiced."
He also cites a litany of cures, from copper bracelets to brain surgeries, that have proved in controlled testing to have no more than placebo effect.
One recent cautionary tale in the addiction field is anesthesia-assisted "ultra rapid detox" for heroin addicts. This method, billed as a fast, painless way to get through withdrawal from heroin and other opiates, became popular in the late 1990s.
One version of this process was developed by Juan Jose LeGarda, the Spanish researcher whose theories led to Prometa.
But in August 2005, a study published in the issue of the Journal of the American Medical Association found that the treatment can be life-threatening, is not pain-free and has no advantage over other methods in keeping people drug free in the long run.
That reversal comes as no surprise to NIDA's Vocci.
“In the absence of well-controlled studies … people may swear that they feel better,” he said. “(But) that doesn’t mean there is anything about the procedure that works.”