U of M leads groundbreaking clinical trial of opioid vaccine

Research underway at the University of Minnesota has the potential to change the way substance use disorder is treated. A clinical trial is testing an opioid vaccine, which targets oxycodone.

“Currently, there is no commercial vaccine for opioids,” said Dr. Marco Pravetoni, the principal investigator and associate professor of pharmacology at the University of Minnesota Medical School. “This is the first clinical trial ever of an opioid vaccine that is being conducted in human beings.”

He explained, as with other vaccines, it’s a shot that prompts the body’s immune system to produce antibodies. Those antibodies essentially block oxycodone molecules from reaching the brain.

“Just like a sponge would soak up all available opioids and would act pretty much like an antidote so the patient won’t feel the […] getting high from opioids or the toxicity side effects of opioids, such as respiratory depression, which is associated with overdose,” Pravetoni said.

The U.S. Food and Drug Administration approved the clinical trial in April 2020, after about a decade of development and manufacturing.

Due to delays caused by the pandemic, the first clinical trial patients were enrolled in October 2020.

“It’s pretty significant,” Pravetoni said. “Most of new medications, including vaccines, antibodies and other therapies, they don’t really make it out of discovery phase and even very few make it to essentially late-stage development and phase one clinical trials.”

There are about 20 people at the University of Minnesota lab working on the trial, plus another 100 people across the country.

“There are a lot of potential clinical advantages of vaccine approach,” said Dr. Sandra Comer, a professor of neurobiology and psychiatry at Columbia University. “I’ve been conducting research on developing medications for treating opioid use disorder for close to 30 years.”

She’s overseeing the team administering the vaccine to the seven people enrolled so far, monitoring their response to the vaccine. The clinical trial is expected to enroll 45 volunteers total.

Each participant must be between 18 to 59 years old, currently using opioids and not seeking treatment.

“There are multiple kinds of populations that we could potentially target,” Comer said. “The one that we’re most interested in right now is people with ongoing opiate use disorder.”

According to Comer, the vaccine can be used along with other existing treatments.

“Methadone, buprenorphine, naltrexone — these are all the three currently FDA-approved medications for treating opiate use disorder and they’re all quite effective,” she said. “The problem is that after about six months of treatment with all three of the medications, the relapse rates tend to be about 50 percent […] and what happens is if somebody stops taking these medications? They’re at risk of overdosing, right?”

The vaccine would act as a safety net.

“They could conceivably still be protected by the vaccine from overdosing, for example, and potentially allow us a window of time to re-engage treatment,” Comer said.

The need for additional substance use disorder treatments become even more apparent during the pandemic.

The Minnesota Department of Health reports 1,008 people died of a drug overdose statewide in 2020. Opioids were involved in 654 of those deaths.

From 2019 to 2020, there was a 59% increase in opioid-involved deaths in the state, according to MDH.

Data also shows there was an increase in opioid-related hospitalizations as well, with 1,164 additional non-fatal overdose-related emergency room visits in 2020 compared to 2019.

“The situation in the United States worsened a lot,” Pravetoni said. “We really need something that will actually protect the public.”

The timeline of the clinical trial will depend on the enrollment and data collected. If the vaccine is ultimately approved, the researchers hope to use it proactively too.

Comer explained that if a teenager suffers a sports-related injury and is prescribed a high dose of an opioid, they could be given the vaccine as well to prevent an addiction from forming.

They are also using the oxycodone vaccine framework to develop a similar antidote to fentanyl and heroin. The goal is to eventually develop a combination vaccine that protects against oxycodone, heroin and fentanyl.

“We could also consider administering this vaccine for first responders, for example, who might be a risk of exposure to something like fentanyl in the line of work that they do,” Comer said. “Or, it could potentially have applications for military personnel.”

Each would require its own clinical trial.

Pravetoni said the results of this first trial are promising.

“It’s very exciting,” he said. “People normally think of vaccines for infectious diseases and now vaccines have been developed for Alzheimer’s, Parkinson’s, cancer and all sorts of different types of disease. And now, we are adding substance use disorder to this portfolio and I think this will open up options that really improve public health.”