Researchers are expected to begin human clinical trials in early 2024 to test the safety and efficacy of vaccines to prevent heroin and fentanyl overdoses. While there is still a way to go, if approved, the vaccines could revolutionize the treatment of opioid addiction and reduce the number of deaths resulting from overdose.
Opioids – especially synthetic opioids – are the main driver of drug-related overdose deaths. The availability of drugs like heroin and fentanyl continues to feed the problem of opioid dependence and places users at risk of death. They’re also difficult drugs to quit.
Drug use and associated overdoses not only burden the loved ones of the person who died, but they also inflict an economic burden. In 2017, the costs for opioid use disorder and fatal opioid overdose in the US were estimated to be US$1.02 trillion.
While the streets are unlikely to ever be clear of drugs like heroin and fentanyl – and, even if they were, they’d probably be replaced by other, equally damaging drugs – researchers at the University of Montana (UM) are close to trialing the next best thing in tackling the opioid epidemic: vaccines to prevent fentanyl and heroin overdose and aid in treating opioid dependence.
The development of the vaccines began with Marco Pravetoni, a professor of psychiatry and behavioral sciences at the University of Washington, who, along with his research team, has been working on vaccines against opioids for more than 10 years.
“Our vaccines are designed to neutralize the target opioid while sparing critical medications such as methadone, buprenorphine, naltrexone and naloxone, which are used in the treatment of opioid addiction and reversal of overdose,” said Pravetoni.
Pravetoni’s team is responsible for developing haptens, small molecules that, when combined with a larger carrier such as a protein, elicit the production of antibodies against target opioids.
In working on these novel anti-opioid vaccines, Pravetoni collaborated with UM researchers who provided the adjuvant, an ingredient that boosts vaccine effectiveness by enhancing the body’s immune response. In this case, a patented adjuvant called INI-4001.
“Our adjuvants improve the vaccine response, providing a stronger and more durable immunity,” said Jay Evans, who directs the UM Center for Translational Medicine and is the co-founder of Inimmune, the corporate partner charged with scaling up vaccine components for manufacture.
The US National Institutes of Health (NIH) provided full funding to UM to develop and advance two opioid vaccines through phase 1 clinical trials as part of their Helping to End Addiction Long-term (HEAL) initiative.
“The human clinical trials will include a drug challenge to evaluate both safety and efficacy of the vaccines in early clinical development,” Evans said. “We will also follow the patients to evaluate how long the antibodies against opioids will last.”
To support the move to human trials, the vaccines have been tested in trials on animal models. The results of the fentanyl vaccine preclinical trial were recently published in the journal NPJ Vaccines, while te results of the heroin vaccine trial are forthcoming.
The researchers expect to finalize their Investigational New Drug applications to the US Food and Drug Administration (FDA) later this year.
“We anticipate testing our vaccines in humans in early 2024,” Evans said. “The first vaccine will target heroin, followed shortly thereafter with a fentanyl vaccine in phase 1 clinical trials. Once we establish safety and efficacy in these first clinical trials, we hope to advance a combined multivalent vaccine targeting both heroin and fentanyl.”
The phase 1 trials will be conducted at Columbia University in New York City and will involve a gradual escalation in dose.
“We start with the lowest dose – a dose that may not be effective,” said Evans. “Phase 1 clinical trials are focused on safety. When the first dose cohort is complete, a data safety monitoring board reviews the data and approves testing at the next dose level if the vaccine is safe. The process takes time until you reach dose levels that are both safe and effective.”
Phase 2 trials will follow to determine things like the number of doses needed to be effective and the amount of time required between doses. Then Phase 3, the important efficacy study involving many participants that the FDA uses to determine whether to approve a drug, based on whether its benefits outweigh its potential risks.
“It takes a long time – years – to get a final approved product,” Evans said. “Based on the efficacy data we see in our preclinical data and the established safety profile in animal models, we are very hopeful that these vaccines will be successful. But there is still a lot of work to be done.”
Source: University of Montana