Pharma's Fraught Quest for Addiction-Med Pay Dirt
The Fix examines the medical, moral and monetary decisions that Alkermes made to bring its drug Vivitrol to market—including a controversial trial in Russia. Are the critics right to cry foul?
In Part One of this investigation, The Fix evaluated Vivitrol's effectiveness.
Drugs are commercial products, and drug companies make a profit or die. In the late ‘90s, a Boston biotech called Alkermes picked naltrexone, an anti-craving addiction drug, as its first potential product. Alkermes’ specialty was making extended-release, longer-acting versions of existing drugs. Naltrexone was in dire need of this makeover: Alcoholics and opiate addicts were having a hell of a time taking the daily pill consistently, further compromising its modest effectiveness.
Using its space-age technology, Alkermes turned the one-a-day pill into a once-a-month injection. The resulting naltrexone shot comes packaged in tiny spheres made of polylactide-co-glycolide (PLG), a polymer often used in medicine. As the sphere decays, the naltrexone seeps into the blood at a steady rate, delivering a consistent dose for 30 days.
That’s pretty cool technology. But even cooler, for Alkermes, was the potential payoff. There are more than 20 million alcoholics and 1 million drug addicts in the US, according to estimates by the National Institutes of Health (NIH). Recovery rates are dire. Most addicts never access a treatment program, and those who do often relapse repeatedly. The costs in health and healthcare terms alone are staggering. At the time Alkermes overhauled naltrexone, the opiate painkiller market was exploding, with dark predictions of a corresponding spike in abuse, addiction, overdoses and deaths. (The reality has since exceeded those fears.)
And it was virgin forest: Naltrexone was one of only a handful of addiction medications, all mediocre.
As anticipated, Alkermes’ first drug—bearing the peppy new name Vivitrol—got FDA approval for use against alcohol dependence in 2006 and against opiate dependence in 2010. Its price tag is memorable: $1,100 for one shot. After spending hundreds of millions of dollars on the development of Vivitrol, the company wanted payback.
But Vivitrol is not selling very well. Last year, sales barely topped $40 million. A mere 1,100 US doctors in 400 facilities, according to Alkermes, currently prescribe the injectable. About half of all prescriptions are written by just 130 physicians.
"There aren't many doctors using it, and I don’t understand why not," says one of those 130 doctors, Robert Woolhandler, a Pittsburgh addiction specialist who has given some 3,000 Vivitrol shots. "Why aren't more rehab clinics using it? After all, when you take away the cravings, you can start tackling the disease."
One reason patients are staying away is, of course, that $1,100 price tag. Marc Fishman, MD, medical director at Maryland Treatment Centers and a professor of psychiatry Johns Hopkins University School of Medicine, agrees. “Right now there’s very poor penetration of insurance coverage, but that’s improving,” he says. “Most of my patients are middle-class or underserved, and if there’s no insurance coverage for Vivitrol, then it’s not an option.”
“It was no easier to keep the opioid addicts taking the Vivitrol injection agent over time than the oral naltrexone," addiction specialist Kyle Kampman said.
Large private insurers, such as Aetna and Blue Cross Blue Shield, offer partial coverage, and $500 a month seems to be the industry average. This leaves you with a $600 copay. Alkermes offers a Vivitrol Value Program that covers up to $500 a month for copays and deductibles for eligible patients, according to Jennifer Viera, Alkermes’ PR rep.
Some top doctors vouch for Vivitrol’s ability to promote better compliance. “My patients say that every time they hold [a naltrexone] tablet in their hand, they get a craving—they know if they don’t take it that day, they can get high,” says Herbert Kleber, MD, director of the division on substance abuse at Columbia University’s medical school. “You don’t totally remove that feeling with Vivitrol, but at least you’re pushing it down the road for a month.”
Yet the pocketbook issue dictates that many doctors prescribe generic naltrexone instead of Vivitrol. Alkermes could improve Vivitrol’s biggest selling point—better compliance than oral naltrexone—by doing a head-to-heard trial comparing the two drugs. Proof of superiority could tip the balance.
No comparison trial is in the works, however. Why? “This question might seem meaningful on its surface. However, clinically, the comparison does not realistically apply,” Alkermes said in an e-mail to The Fix. Their reasoning appears to lie in a technicality: Naltrexone was approved for blocking opiates' effects “but not actually for the treatment of opioid dependence.” Both drugs are, of course, prescribed for the treatment of a disease in people, not as a science experiment in brain receptors.
But Alkermes may have another reason to beg off a comparison. In 2008, at the request of the FDA, the company ran a safety trial that pitted Vivitrol against naltrexone. It’s safe to say that the results did not deliver the headlines that Alkermes had hoped for.
The study, which lasted 48 weeks, included 315 patients who were addicted to alcohol, 69 to opiates, and 52 to a mix; one group got a shot of Vivitrol every four weeks and the other got a daily naltrexone pill. At the end of the study, half of the patients in both groups had dropped out, although the naltrexone group stuck it out for 36 weeks—eight weeks longer than the Vivitrol-takers. In addition, 40% of the alcohol-dependent patients completed the study, compared to 30% of the people addicted to opiates or to both.
These results underwhelmed some leading addiction specialists with doubts about Vivitrol’s “better compliance” claim. “It was no easier to keep the opioid addicts taking the injection agent over time than the oral drug," Kyle Kampman, MD, medical director of the Charles O’Brien Center for Treatment of Addictions at the University of Pennsylvania, reported when the study was first presented 2008.
Another critic, Meera Vaswani, MD, of the All-India Institute of Medical Sciences in New Delhi, said, "I question whether there is a need for [Vivitrol], in the absence of a clear efficacy advantage." If anything, she viewed the injection aspect less as less of a selling point than, well, a sticking point: “Anything that's invasive is not appreciated." Before she would prescribe Vivitrol, Vaswani said, it would have to earn an "extra point.”
In an interview with The Fix, David Gastfriend, MD, vice-president for scientific communications at Alkermes, dismissed these criticisms, arguing that compliance could not be fairly judged in a test of safety. “In a safety study, you're trying to get as many adverse effects as possible," he says. "Therefore, it doesn't reflect the real world.”
In the study it conducted to win approval for Vivitrol for opioid dependence, Alkermes managed to raise the hackles of addiction activists. The company chose to locate the trial in Russia—a curious decision, since the US has no shortage of junkies and pill heads. But given the mounting research showing that naltrexone my be no better than methadone, Suboxone or placebo, Alkermes may have seen it as a wise move.
- Timothy Fong
- UCLA Addiction Clinic
- Robert Woolhandler
- Marc Fishman
- Maryland Treatment Centers
- Johns Hopkins University School of Medicine
- Blue Cross Blue Shield
- Jennifer Viera
- Vivitrol Value Program
- Herbert Kleber
- Kyle Kampman
- Charles O’Brien Center for Treatment of Addictions
- University of Pennsylvania
- Meera Vaswani
- All-India Institute of Medical Sciences
- American Journal of Managed Care
- James Garbutt
- Alcohol and Substance Abuse Program
- UNC-Chapel Hill
- Soros Foundation
- Daniel Wolfe
- The Lancet
- Andrew Tatarsky
- moderation management
- Richard Pops
- Boston Magazine.
- Walter Armstrong