Vaccine for FENTANYL and heroin to enter human trials in 2024: Shot would be given to high-risk drug users months in advance
Fatal claims the lives of tens of thousands of Americans each year in what experts have described as the “worst crisis the US has ever faced.”
But it could be a thing of the past thanks to a new vaccine that would be given to high-risk drug users months or possibly years before an overdose.
The vaccine — which will likely be administered through multiple injections — essentially teaches the immune system how to prevent opioids from cutting off the oxygen supply to the brain.
Researchers say they expect human trials to begin “early 2024.” The fentanyl vaccine would be different from the antidote Narcan, which is administered in case of overdose and has already been approved by the Food and Drug Association (FDA).
Molecular biologist Jay Evans of the University of Montana (above) expects his group’s vaccines against heroin and fentanyl to be tested in humans “early 2024.”
Both heroin and fentanyl bind to opioid receptors in brain regions that control pain and emotions. During an overdose, the brain is deprived of oxygen, killing neurons. An opioid vaccine would neutralize the chemical with antibodies while it is still in the bloodstream
In animal studies, inclusive one published in July in the Nature journal npj Vaccinesthe researchers were able to show that such anti-fentanyl vaccines could be improved by the addition of a second small molecule called an adjuvant.
But those tests will need to be safe and repeatable in humans before anyone can line up for their own injections.
The team, led by researchers at the University of Montana, has actually developed two new vaccines, with the second targeting heroin overdoses.
Both heroin and fentanyl attach to parts of the brain that control pain and emotions and dampen them. But during an overdose, these chemicals deprive the brain of oxygen, killing neurons.
The new vaccines, similar to competitive research on fentanyl vaccines elsewhere, are designed to neutralize opioid chemicals with antibodies while these compounds are still in the bloodstream.
“Once we establish safety and early efficacy in these initial clinical trials,” says molecular biologist Jay Evans of the University of Montana (UM), “we hope to advance a combined multivalent vaccine that targets both heroin and fentanyl.”
America is currently in the middle of a fentanyl epidemic, with about 150 Americans dying each day from the synthetic opioid according to the US Centers for Disease Control and Prevention (CDC).
The CDC estimates that among the 107,081 drug overdose deaths reported in the United States in 2022, over two-thirds, or over 72,000, can be attributed to synthetic opioids such as fentanyl.
Evans, who also co-founded the start-up Inimmune designed to market these drugs, has focused his U-M team on creating more adjuvants, substances they hope will further increase the effectiveness of the vaccines. will increase.
“Our adjuvants improve vaccine response and provide stronger and more durable immunity,” said Evans, whose official title is director of U-M’s Center for Translational Medicine.
Evans’ UM team patented the adjuvant INI-4001, which will be just one facet of the final vaccine cocktails.
Fentanyl has overrun a number of American communities and was responsible for 71,000 drug overdose deaths in 2021. Pictured: A homeless man in Seattle, Washington smokes fentanyl
“We have worked closely in recent years with researchers from Inimmune, the University of Minnesota, the University of Washington, Hennepin Healthcare Research Institute and Columbia University to design and optimize anti-opioid vaccines for advancement in human clinical trials,” said he. .
The vaccine itself works by stimulating T cells in the immune system to make antibodies that bind to fentanyl in the bloodstream.
These immune proteins capture the drug as soon as it enters the body and prevent it from spreading further and causing damage. It is then processed in the kidneys and flushed out of the body.
“Antibodies produced through active immunization with an anti-opioid vaccine sequester opioid in the blood and prevent it from crossing the blood-brain barrier,” said Evans’ research partner Dr. Marco Pravetoni at the University of Washington, where he directs the Center for Medication Development for Substance Use Disorders.
“The first vaccine will focus on heroin,” Evans said, “followed shortly by a fentanyl vaccine in phase I clinical trials.”
These Phase 1 human trials, he noted, will be conducted by the group’s collaborator, Dr. Sandra Comer of Columbia University in New York.
Finding the right subjects, patients currently on fentanyl or heroin, could take six months or more.
And the process will have to be slow to protect the health and safety of these human subjects.
Phase 1 trials will involve a very gradual escalation in vaccine dosing, according to Evans.
“We start with the lowest dose, one that may not be effective,” Evans said.
“Phase I clinical trials are focused on safety. When the first dose cohort is complete, a data safety committee 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.”
Evan added that Dr. Comer and others will also follow the trial patients to evaluate “how long the opioid antibodies will last.”
If these tests prove successful and safe, phase 2 human trials will rise to the challenge of figuring out details such as the number of doses needed for effective protection against overdoses and the appropriate time needed between doses.
Then would come Phase 3: a large cohort study with many participants, designed to help the FDA decide whether the vaccine’s life-saving benefits outweigh the potential risks of side effects.
But a similar vaccine, targeting the prescription opioid oxycodone, is already paving the way for the heroin and fentanyl vaccines.
Evans’ research partner Dr. Pravetoni of the University of Washington brought in the oxycodone vaccine Phase I trials with Dr. Comer in Columbia in 2021.
“Our vaccines are designed to neutralize the target opioid while sparing critical drugs such as methadone, buprenorphine, naltrexone and naloxone,” Evans noted, “which are used in the treatment of opioid dependence and overdose reversal.”
That needle is inserted through so-called “haptens” and “drug conjugate” vaccines, developed by Dr. Pravetoni, which can trigger the body’s immune system to produce antibodies against only target opioids.
While these breakthroughs have seen great success in animal testing and other lab-scale experiments, Evans cautioned that many regulatory steps need to be taken before these vaccines can start helping users who are currently at risk.
“It takes a long time – years – to get to a final approved product,” he said.
“Based on the efficacy data we see in our preclinical data and the established safety profile in animal models, we are hopeful that these vaccines will be successful. But there is still a lot of work to be done.’