Can an Implant Stop Heroin Addiction?
Four toothpick-sized implants that deliver a steady dose of buprenorphine into the upper arm may be the future of drug treatment—could they end America’s heroin problem too?
Buprenorphine, the active ingredient in the new implant, has been the drug of choice for combatting what has become an unprecedented opioid epidemic in the U.S. From 1999 to 2008, the rate of overdose deaths from painkillers and heroin quadrupled. Today, at least 2.1 million Americans are struggling with addiction to drugs like Oxycodone; more than 400,000 are dependent on heroin.
Probuphine is not so much a new drug as a new delivery method for buprenorphine, the old one. Nicknamed “bupe,” it’s an opioid derivative whose efficacy in clinical trials earned it the title “the wonder drug.” Buprenorphine works by binding to the same opioid receptors as drugs like heroin, without producing the high.
Sold under the name Subutex (or, when combined with the drug naloxone, Suboxone), it has given those dependent on opioids a fighting chance at recovery, allowing them to get off more dangerous opioids without the debilitating effects of withdrawal.
But despite its efficacy in clinical trials, the rates of success among users is low, in some cases less than 10 percent. The problem isn’t the medicine but the organization that taking it every day requires. For the average American, sticking to a medical regimen is tough (according to a 2011 study up to 75 percent don’t). For someone in the psychological grip of addiction, it’s near impossible.
Beyond failure to adhere to the prescription, pills open up the potential for a host of other problems. Among them, patients taking a few days off to get high, consuming higher doses than prescribed, and even selling it on the black market.
Probuphine, an implant that delivers six months of steady buprenorphine, may be the answer the drug treatment world has been looking for. Understanding the implant begins with understanding its active component, buprenorphine. Synthesized in 1969, the drug first gained approval for opioid dependence in 2002—the first drug to gain approval under the Drug Addiction Treatment Act.
When the drug was first released, many hoped it would usher in the end of a growing opioid epidemic. With more people addicted to opioids than ever before, and 46 people dying from overdoses each day, it’s safe to say the plan has yet to work.
Researchers at Harvard University analyzed why in the first large-scale study of opioid treatment at Harvard University in 2011. Their results reflected what doctors had been reporting. Close to 50 percent of patients were able to get off opioids during 12 weeks of suboxone treatment. But when they stopped it, relapse rates skyrocketed. In the end only 8.7 percent of the participants stayed in recovery.
Considering the implant’s potential to eliminate abuse and misuse, it would seem that the company who created it, Titan Pharmaceuticals, did it out of necessity. On the contrary, they’ve been pursuing it longer than Subutex or Suboxone have been on the market.
The drugmakers found a solution to problems that didn’t exist—but now do. Titan's President and CEO Sunil Bhonsle says the company had begun work on the drug before buprenorphine was approved in the U.S. The implant, a non-biodegradable drug delivery system, is called ProNeura.
“We licensed the patent from MIT back in 1996, but the product itself is something we thought of and started in 2000,” Bhonsle tells The Daily Beast. “At that time [buprenorphine] was just being talked about and early clinical studies had been done. It had success in France and Australia but not yet in the U.S.”
Bhonsle and his team initially worked on an implant to treat schizophrenia, something he still hopes to pursue. But eventually they turned to addiction because of how it aligned with the needs of those trying to get off drugs. “We felt addiction was an area where this could be very applicable because maintaining long-term treatment was necessary,” he says. “Compliance is a very strong factor and so that’s how the idea came about.”
Dr. Kate Beebe, chief development officer at Titan, expanded on the difficulty of a daily pill. “Buprenorphine is a really good drug, it’s very effective, but there are issues with the pill form,” she tells The Daily Beast. “When you give an addict a pill to take every day it’s difficult physiologically...you can forget to take it, etc.” When it comes to drug addicts, she says, the stakes are higher.
“It’s dangerous for someone with opioid dependence. The relapse rate is 60 to 80 percent for people who don’t have access to the medicine,” says Beebe. “Plus, people who take the oral form can control when they take it. They can have a party weekend and then take it Monday morning—that’s dangerous too.”
The downfalls of an oral form of buprenorphine was one of the central themes of the FDA hearing on probuphine on Jan. 12 of this year. The main clinical study presented in the hearing was a single, double-blind, active-controlled trial in which half of the 176 patients were given a real probuphine implant. Among those with implant, 88 percent tested negative for the presence of illicit opioids (compared to 72 percent in the control).
At a public hearing follow the presentation, recovering drug addicts, treatment specialists, and medical experts argued in favor of the drug’s approval. Among them, two fathers who described their sons’ overdoses and one of the clinical trial’s participants, Scott Jernigan. A businessman turned painkiller addict, Jernigan described how trying the implant had changed his life.
“What the implant does is take away the reminder of how I screwed up every day, and the worry about missing my medication,” he told the committee. “I don’t have to go to the pharmacy to get the look, ‘Oh, you are one of those.’” Adding later: “I’m president of my own company again, I’m not a dirty junkie. But I need help. With the implant it will be one less hurdle for us as addicts to get over.”
Dr. Rick Rosenthal, co-principal investigator of the trial and the Medical Director of Addiction Psychiatry at
Mount Sinai Behavioral Health System, echoes the sentiment. “It takes adherence off the table. It allows them to concentrate on learning to live a life without these drugs,” he tells The Daily Beast. “Which is where recovery happens.” The advisory committee agreed with Rosenthal’s view, ruling 12-5 that the benefits of probuphine outweigh the non-fatal side effects.
Not everyone in the room supported the decision. Dr. Tracy Rupp, director of Public Health Policy Initiatives at the National Center for Health Research, spoke out against it at the hearing. Rupp was concerned about missing urine samples, which she says were counted as negative, and said the all-white study participants weren’t representative of the demographic. Plus, she worried, the drug could take weeks to reach stable levels—putting patients at risk of relapse. Others in the hearing voiced concerns that patients might tear it out of their arms.
More than two months later, her concerns around the safety of the drug remain.
“The probuphine implant was studied in only 87 patients for 6 months,” Rupp wrote to The Daily Beast. “This is not a large enough study to get a good understanding of the risks posed by this new form of treatment, nor is it of sufficient duration to understand the risks involved in placing a new implant every 6 months, in some cases for years.”
In the final conclusion of her testimony, Rupp told the advisory committee at the FDA that she was “disappointed to conclude” that the evidence wasn’t enough for her to endorse the drug. "While we all desperately want new treatments for opioid abuse, we have to be sure they are safe and effective,” she said.
Rosenthal expressed shock at her claims, calling them “simply untrue.” He says that while a total of 87 patients received probuphine in the last clinical trial, a cumulative total of 370 unique subjects have been treated with probuphine in clinical trials over the past nine years. There have been zero incidences of participants ripping the drug out from under the skin. And in regards to Rupp's statements about the delayed effect, Titan says the drug reaches peak levels that are very effective within the first day and then slowly subside to a stable level and remain that way for six months.
Beyond that, he notes that the drug’s active ingredient, buprenorphine, has been on the market for more than a decade. “The point is that there is a new vehicle to deliver an old medicine,” says Rosenthal. “It’s kind of a no-brainer, it makes sense.” Whether or not the implant has the power to end the heroin epidemic, Rosenthal isn’t yet convinced. Getting rid of the root problem, the availability of opioids, is key. Still, he’s excited by the new development and looks forward to seeing where it will go. “I’ll ride any horse that’s going in the right direction in terms of medication for addiction,” he says. “I think this is a strong one.”
CORRECTION: An earlier version of this article stated that Titan paid for the Phase 3 trial, it was actually Titan's commercialization partner, Braeburn Pharmaceuticals. Dr. Tracy Rupp also did not express concern about patients ripping the implants out of their arms, it was others at the hearing who did so. Her original comment that the implant takes awile to "kick in" has been clarified to state that it takes 3-4 weeks for the drug to reach stable levels—something that Titan denies.