Backed by millions of dollars in federal funding, researchers envision vaccines and monoclonal antibody treatments as a complement to opioid treatments and overdose drugs, but promising treatments will not be available until It could take years.
The federal government recently awarded an additional $14.8 million to research into a monoclonal antibody that targets fentanyl, the nation’s deadliest street drug, by binding to molecules before entering the brain and stopping people from breathing. . Cessation Therapeutics, a North Carolina biotech company, promotes its monoclonal antibodies as a means to both prevent overdoses and treat overdoses and opioid addiction.
“It makes it spongy. It’s like Pac-Man,” said Andrew C. Barrett, the United States’ chief scientific officer. Cessation Therapeutics recently began Japan’s first government-approved human clinical trial. Injection of a monoclonal antibody targeting fentanyl.
Monoclonal antibodies (proteins that are brewed from cells in giant vats under controlled conditions) have been used for decades to treat cancer and autoimmune diseases, even though the drugs are expensive. has brought about change. Before the advent of coronavirus vaccines, antibody drugs had proven effective against pandemic pathogens, drawing attention to their potential to treat other infectious diseases.
Clinical trials are also underway for monoclonal antibody treatments for methamphetamine, a stimulant that is increasingly used in combination with fentanyl.
At the same time, clinical trials of vaccines approved by the Food and Drug Administration continue. Oxycodone, the prescription painkiller that has sparked this country’s opioid crisis. Researchers also heroin and fentanyl.
This effort reflects the urgency of the drug crisis, but that urgency faces harsh realities. Similar research has been stymied for decades. Research costs a lot of money, but that doesn’t take into account the cost for companies to bring antibodies or vaccines to market. It also takes time, as the illicit drug landscape is rapidly evolving, with new synthetic substances emerging faster than researchers can study them. And skeptics argue that if they could afford the high cost of antibody treatments, drug users would not consent or would simply switch to other substances.
“People have to say they want to get a shot, and they have to choose to keep going for every shot and every IV,” said Keith Humphries, a professor of psychiatry at Stanford University and a former White House drug policy adviser. says. “Vaccines do not reduce cravings or withdrawal symptoms or provide an incentive for someone to return for more treatment.”
The drug buprenorphine exists to reduce cravings for opioids and is a monthly injection of a non-opioid that binds to receptors in the brain, said Ryan Marino, an addiction expert and assistant professor at Case Western Reserve University School of Medicine. One person noted that Vivitrol blocks euphoria. Produced by opioids.
Marino argued that resources should be spent on expanding access to existing drugs and the overdose-reversing drug naloxone, rather than vaccines. “Putting money and resources into moonshots like that has failed time and time again. It’s a little disappointing to me,” he said.
long history of research
For decades, scientists have been searching for How to use antibodies to block the harmful effects of street drugs. In the 1970s, researchers developed a vaccine to block the effects of heroin in rhesus monkeys trained to self-administer the drug. research, published A 1974 paper in Nature was promising, but it also showed that high doses of heroin could inhibit antibodies.
Research declined with the introduction of methadone, an opioid drug that treats heroin craving. In subsequent decades, researchers with a deeper understanding of the science of addiction focused on public health threats such as cocaine and nicotine.
Vaccines given by injection will placate the immune system and cause it to produce antibodies to fight off invaders. But the targets will not be viruses, but addictive drug molecules. These molecules are usually too small to trigger the production of antibodies.To solve To solve this problem, researchers add molecules that resemble larger proteins, essentially tricking the immune system into producing antibodies.
For many years, vaccines have not produced enough antibodies. And when it comes to vaccines against nicotine, the antibodies don’t bind tightly enough to the molecule and remain in the body for a long time, says Kim, a chemist at Scripps Research who has worked on vaccines and monoclonal antibodies for decades. Janda said.
“I think there’s probably been 30 to 40 different nicotine vaccines tried so far, and they’ve all failed,” Janda said.
A highly touted potential vaccine is NicVAX. it didn’t work In 2011, the developer revealed that it was superior to a placebo in a clinical trial of 1,000 smokers.
Efforts to develop a vaccine against cocaine have also stalled. In one case, trial results published in 2014 showed that only about 63% of a group of 150 people who received the vaccine developed sufficient levels of antibodies, the researchers said. said Thomas R. Kosten, professor of psychiatry and immunology at Baylor College of Medicine, who conducted the study.
“That alone was not enough for FDA approval,” Kosten said. “They wanted something like 80 or 90 percent.”
Kosten is working on a fentanyl vaccine and hopes it will be ready for clinical trials soon.
Researchers said they believed vaccine production would be small. Antibodies are needed to attack fentanyl.
Although this drug is very powerful, it is usually taken in small doses. Marco PravetoniHe is the director of the Center for Drug Use Disorder and Overdose Drug Development at the University of Washington, where he is working on developing vaccines for fentanyl and heroin.Vaccines may be particularly helpful Pravetni said it’s for drug users who are concerned that their drugs, such as cocaine, are tainted with fentanyl.
“This vaccine could be almost perfect for occasional users,” said Pravetni, who is also working on clinical trials of an oxycodone vaccine with researchers at Columbia University.
Professor Pravetoni is also researching fentanyl monoclonal antibodies, which some scientists believe have greater potential than vaccines.
Supporter discuss it Monoclonal antibodies (administered by IV infusion or shot) can be designed to work overwhelmingly and quickly, but it takes weeks and several shots for a vaccine to generate enough antibodies to fight the drug. You may need it.
“Monoclonal antibodies are a safer option in many ways,” said Nora Volkow, director of the National Institute on Drug Abuse, which is funding both studies.
Not everyone is so into it. Skeptics point out that monoclonal antibodies will only last a few weeks. Even if they are less effective, the vaccines will last longer and cost less. Stanford University’s Humphreys said antibody treatments can be too expensive to synthesize, inject and monitor.
“In the case of stimulants and cocaine, for which we don’t have a cure, the cost may be justified. But there are many cheaper and more effective alternatives, and patients, private insurance companies… Who in Medicaid is going to pay for the opioids?” Humphries said.
And the following questions remain: Whether users at highest risk of overdose desire frequent treatment. Fentanyl users may switch to another opioid with a different chemical composition.Cocaine users may move to another stimulant such as crystal meth. Or use more cocaine.
“If someone decided to take cocaine, they would be able to overcome the antibodies. But they would need to use even more cocaine to do that. So what really works is the ability to quit.” Only those who are willing.” Andrew B. Normanresearchers at the University of Cincinnati are developing a monoclonal antibody that targets cocaine.
The quest to treat stimulant use
More clinical trials are underway for a monoclonal antibody treatment for a stimulant that causes overdoses and is not similar to opioids. trigger. Chronic overdose of stimulants can cause symptoms such as agitation, paranoia, increased body temperature, chest pain, increased heart rate, and heart failure.
InterveXion Therapeutics, a Little Rock biotechnology company, has received approximately $60 million in federal funding and completed two Phase 2 trials. in one studyThe researchers gave dozens of participants a small amount of stimulant along with an antibody and measured how it changed the concentration of the stimulant.
W. Brooks Gentry, the company’s chief medical officer, said researchers found that meth levels in the bloodstream were actually elevated, which is because antibodies move meth molecules away from the brain and heart. It is said to be a signal indicating that the person is pulling out. The molecules then leave the bloodstream and are eventually metabolized through the liver and kidneys, he said.
Other trials of monoclonal stimulant treatment are being conducted in conjunction with cognitive behavioral therapy.
Gentry cautioned that the antibodies are designed to significantly reduce the effects of stimulants and do not reduce cravings.
“We are trying to increase the number of trials. [patients] We need to stop using it,” Gentry said. “They don’t get the positive reinforcement effects. They feel like they never had anything.”
The company estimates it will take at least another five years and additional research to obtain regulatory approval. Gentry said it’s too early to predict how much the infusions will cost. It may be approved in the future, but for now it could cost between $1,500 and $2,000.
Cessation Therapeutics is touting its monoclonal antibodies as a way to prevent overdoses of fentanyl and related substances. Up to 50 times more potent than heroin, fentanyl is the leading cause of death for Americans ages 18 to 49, according to a Washington Post analysis. An estimated 5.6 million people ages 12 and older have suffered from opioid use disorder within the past year, according to a 2021 federal study. data.
Opioids attach to receptors in the brain and slow or stop breathing, which can be fatal. Barrett, the company’s chief scientific officer, said the monoclonal antibody binds to fentanyl molecules before they can slip through the tightly locked layers of cells that prevent the substance from entering the brain.
The antibodies would also ablate the molecules that reach the brain, reversing the overdose, he said. Experts say the treatment is not practical for emergency use. Naloxone is often formulated into nasal sprays that are currently available over the counter and are commonly used by emergency personnel, family members, and even passersby to quickly revive the user.
Instead, researchers envision antibodies as an additional layer of protection that could prevent future overdoses and act as an adjunct to therapeutic drugs, Barrett said.
The federal funding announced Oct. 18 will go toward research into monoclonal antibodies that can be administered by injection, and was previously awarded to research into an infusion that the FDA approved for initial clinical trials in July. Added to $7.1 million.scientist Researchers at the Integrative Neurochemistry Laboratory at McLean Hospital, a psychiatric hospital in Boston, plan to test the antibodies in animals.
So far, six subjects who do not have addiction problems have received the antibodies. Barrett said the data has not yet been published, but there have been no side effects. The Phase 2 trial will involve administering the antibody to healthy participants followed by medical-grade fentanyl. The “pivotal” study will involve patients who already suffer from: Opioid use. Barrett said if the trial is successful, the company could ask the FDA for accelerated approval by early 2026.