A partnership involving a team at the University of Montana, funded by NIH, suggests that it is “nearing human trials” for vaccines designed to prevent fentanyl and heroin drug overdoses. Expecting to begin testing in humans in early 2024, the researchers will target first heroin, then fentanyl, before attempting a combined multivalent vaccine against both.
Drugs and overdose deaths
The NIH suggests that over 106,000 US deaths were attributed to drug overdose in 2021. This is an increase from 2019 and was reflected in a rise in deaths involving “synthetic opioids” such as fentanyl. 70,601 synthetic opioid overdose deaths were reported in 2021. Fentanyl is a “powerful” synthetic opioid that, although FDA-approved for severe pain management, is “increasingly found in the drug supply” as illegally made and distributed. It is “about 50 to 100 times more potent than morphine”.
The journey of vaccine development
Dr Jay Evans directs the UM Centre for Translational Medicine and is co-founder of Inimmune, the corporate partner focused on scaling up vaccine components for manufacture. He suggests that the vaccines began with Dr Marco Pravetoni, professor of psychiatry and behavioural science and the University of Washington, and director of the Centre for Medication Development for Substance Use Disorders. His team designs haptens and drug conjugate vaccines to elicit the production of antibodies against target opioids.
Dr Pravetoni has been tackling vaccines against opioids for “over a decade”.
“Our vaccines are designed to neutralise the target opioid, while sparing critical medications such as methadone, buprenorphine, naltrexone, and lanoxone, which are used in treatment of opioid addiction and reversal of overdose.”
Dr Evans and his team are bringing a patented adjuvant, INI-4001, to the mix. Having worked closely with other researchers, Dr Evans hopes to “optimise anti-opioid vaccines” to advance them to human clinical trials.
“Our adjuvants improve the vaccine response, providing a stronger and more durable immunity.”
With a $33.4 million contract to develop and advance two candidate anti-opioid vaccines through Phase I trials, and support from the NIH Helping to End Addiction Long-Term (HEAL) initiative, the team is prepared for further steps next year. So far mice, rats, and pigs have been tested in advance of human testing.
Trials to begin
Dr Evans believes that the heroin vaccine human trials will begin first and looks forward to finalising Investigational New Drug applications to the FDA later in the year. Phase I trials will be conducted with Dr Sandra Comer at Columbia University in New York City. Recruitment and enrolment could take over 6 months and will include a drug challenge to “evaluate both safety and efficacy”. Patients will then be followed for an evaluation of antibody persistence.
The Phase I trials involve a gradual dose escalation, with the lowest dose possible not being effective. Dr Evans emphasised that these trials will be “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.”
Moving through later trials will take a “long time”, says Dr Evans, but thanks to preclinical data and established safety profiles in animal models, the team is “very hopeful”.
With the potential to save and change thousands of lives in the US alone, these vaccines could be critical if successful in trial. For more on tackling pressing health issues with vaccine approaches don’t forget to subscribe to our newsletter here.