With the United States in the midst of a dramatic rise in opioid overdose deaths – a problem exacerbated by the widespread availability of fentanyl, a synthetic drug estimated to be 50 times stronger than heroin – law enforcement and public health officials are scrambling for solutions.
To address an epidemic, which is killing tens of thousands of people every year in states like Ohio, New Hampshire, and Massachusetts, officials are enacting measures like needle exchange programs, experimenting with rehabilitation over incarceration, and expanding community support networks. Each effort has seen varying degrees of success.
Against this backdrop, researchers at the Scripps Research Institute published results earlier this year about a new kind of therapy that could help curb deaths from fentanyl overdoses. Writing in the journal Angewandte Chemie, the scientists said they succeeded in building a vaccine that protects mice from overdoses of fentanyl by targeting the opioid with antibodies and partially blocking its effects. If proven to be effective and safe in humans, the vaccine could eliminate fentanyl’s pleasurable high by blunting the drug’s effects. That could help prevent addicts undergoing treatment from relapsing.
“The idea is that for people who are undergoing abstinence, hopefully the vaccine would mitigate the relapse potential,” said Kim Janda, a professor and chemist at Scripps who led the research, and who has studied addiction for decades. By targeting fentanyl and opioids that are structurally similar, like acetylfentanyl, Janda says his vaccine is trying “to stay one step up of the drug dealer.”
“We’re trying to come up with a vaccine not only for fentanyl,” he said, “but for the clandestine drugs that are being used as substitutes.”
The vaccine works by presenting mice with a template of the fentanyl target plus adjuvants, or molecules that boost the immune system. That combination elicits an antibody response that binds to fentanyl and other drugs in its class. By attaching themselves to a specific region of fentanyl and its popular derivatives, the antibodies can attenuate the drug’s effects. Janda has shown that his vaccine protects mice from overdoses of fentanyl by reducing the amount of active drug circulating in the mouse’s blood. When he gave the vaccinated mice fentanyl, they survived double to quadruple the dose that would normally kill them.
“I’ve never had any of our vaccines protect from lethal doses except my opioid vaccines,” he said.
In 2013, Janda and his colleagues created a heroin vaccine that works in much the same way as this fentanyl vaccine. Like the fentanyl therapy, it is still in its early stages. But Scripps recently teamed up with Virginia Commonwealth University to test the heroin vaccine’s efficacy and toxicity in primates. He’s hoping to find partners that will help bring the fentanyl vaccine to clinical trials, too. But raising those funds and forming those collaborations, he said, has been his biggest challenge.
“I haven’t been able to partner with any major company that wants to back a heroin vaccine,” Janda said. “All I hear is, ‘It doesn’t really fit our portfolio.’” Insurance companies are happy to pay for people trying to quit nicotine, he said. “They’re not paying for a heroin addict or a coke addict.”
The industry’s misgivings may also be due to the limited success that addiction vaccines have had in clinical trials so far. Though scientists have been working on vaccines for heroin, cocaine and smoking for years, translating the benefits seen in mouse models to humans is difficult. A few years ago, for example, a nicotine vaccine failed in phase III clinical trials when it couldn’t show a significant benefit compared with a placebo. That was the closest that an addiction vaccine has ever gotten to market.
Another hurdle, according to Janda: Despite the $1.1 billion the government has requested to address the opioid epidemic, none of that funding is flowing toward the work he and his team are doing.
“With all this money released to Congress for opioid abuse,” he said, “nothing is coming to basic research.”