Drug overdose deaths rose by close to 30% in the United States in 2020, hitting the highest number ever recorded, according to a report the CDC issued in July 2021. The data indicates more than 93,000 people died from drug overdoses in 2020—a 29% increase from the 72,151 deaths projected for 2019.
While it’s still early in the process, scientists at Columbia University Vagelos College of Physicians and Surgeons have now taken a step toward turning those numbers around. A team at the university is leading a Phase 1a/1b clinical trial for an experimental vaccine for treatment of opioid use disorder. The vaccine is the first to be tested in the United States for such a purpose.
The development team, led by principal investigator Sandra Comer, says that while there is currently medication to treat opioid use disorder, it only has about a 50% success rate in terms of a patient relapsing within 6 months.
“A vaccine that lasts for several months, given in combination with any of these medications, could help many more people beat their addiction and potentially protect them from an overdose death,” said Comer, professor of neurobiology at Columbia University Vagelos College of Physicians and Surgeons.
The vaccine, developed by Marco Pravetoni of the University of Minnesota Medical School, is designed specifically to address abuse of oxycodone by generating antibodies to the commonly abused prescription opioid. For example, if a drug user takes oxycodone after vaccination, the antibodies latch onto the drug and prevent it from crossing the blood-brain barrier. Since the opioid does not reach the brain, the user does not get high. For this reason, the scientists believe the vaccine may also protect against fatal overdose due to respiratory depression.
In preclinical studies, animals that received the vaccine reduced self-administration of the drug and were protected from toxicity and signs of overdose, including the inability to breath.
The Phase 1a/1b clinical trial is being piloted in 24 opioid-using volunteers, before the possibility of expansion to 45 if the vaccine proves safe and shows potential efficacy. For the double-blind trial, one group of volunteers will receive a low dose of the vaccine, one group will receive a high dose and another will receive a placebo.
The primary endpoint of the trial is to determine if the vaccine is well-tolerated and safe, but the team will also examine if the vaccine produces sufficient antibodies to prevent the “high” when the volunteers are given oxycodone.
Blood samples will be taken from volunteers and shipped to researchers at the University of Minnesota, who will conduct pharmacokinetic and immunological testing in the hopes of identifying biomarkers that can predict vaccine efficacy.
Since the chemical structure of different opioids varies so widely—as forensic scientists and toxicologists are well aware—different vaccines are needed for each opioid. Currently, both teams at Columbia and the University of Minnesota are developing versions to work against heroin and fentanyl.
The CDC says deaths related to synthetic opioids played a large role in the overdose explosion seen in 2020. Multiple studies have pointed to elevated drug use and higher-risk usage, such as cutting or mixing drugs from an unreliable supply and using in isolation, as potential factors in the pandemic’s deadly surge.
According to the CDC, the 2020 explosion in overdose deaths was fueled, at least partially, by synthetic opioids like fentanyl. The public health agency estimates synthetic opioid-related deaths likely increased by around 54% last year. For context, in 2015, synthetic opioids were involved in 18 percent of all overdose deaths; in 2020, that appears to be the case in more than 60 percent of deaths.
Photo: Vial of experimental vaccine to prevent oxycodone overdose. Credit: Columbia University Irving Medical Center