A Fentanyl Vaccine Is on the Horizon — If Trump Restores Funding for Its Clinical Trials

Annually, over nine million people misuse opioids in the United States. Opioids are a factor in at least seven out of every ten overdose deaths.

To tackle the public health crisis, researchers are developing vaccines to immunize people against the opioid fentanyl, a potent synthetic opioid often hidden in counterfeit pills and mixed into drugs such as cocaine and heroin. Often taken unknowingly, fentanyl can be fatal because it suppresses breathing.

Scientists are exploring animal and human trials of vaccines and monoclonal antibodies — lab-made antibodies that mimic the natural immune system — to reduce overdose deaths. The plan is to train the immune system to produce antibodies that bind to fentanyl in the bloodstream. By preventing fentanyl from crossing into the brain, scientists hope to reduce its effects and lower the risk of overdose.

Let’s Dig Deep Together.

Subscribe to The Xylom’s free weekly newsletter to get more collaborative, in-depth coverage of global public health solutions.

The Xylom sat down with Marco Pravetoni, professor of psychiatry and behavioral sciences at the University of Washington and founder of Counter X Therapeutics, a biotechnology company developing antibody-based therapies for fentanyl overdose, and Jacques Bouchy, the company’s chief business officer. The conversation explored the future of therapeutics in treating fentanyl overdoses and opioid use disorder, as well as the difficulties in creating these treatments.

This conversation has been edited for length and clarity.

---

Zoe Beketova: Scientists have been working on substance use disorder treatments for decades. What’s been the main challenge in developing an effective treatment?

Marco Pravetoni: It’s been quite difficult to separate therapeutic targets from [addictive] behavior in the mu-opioid receptor. (The mu-opioid receptor is the main brain receptor that opioids bind to. It is responsible for both pain relief and many of the addictive effects of opioids). So, teasing those apart so that the drug doesn’t interfere at all with underlying, normal behavior and well-being is difficult.

ZB: What have you focused on in your work?

MP: My laboratory focuses on discovery, development, and late-stage preclinical work. Counter X Therapeutics is mostly focused on advancing some of our discoveries into clinical development. Right now, the product that is slightly closer to human trials is CTRX-101, a monoclonal antibody [designed] for reversal or prevention of overdoses involving fentanyl and fentanyl analogs.

Jacques Bouchy: I think it’s important to highlight how CTRX-101 works. It binds to fentanyl, blocks it from entering the brain and mu-opioid receptors, and then it blunts all the lethal effects. So, it doesn’t block any sort of biological target. If somebody’s on pain medication, they can still [receive other opioids]. It just keeps fentanyl from doing the really bad things to people. 

Jacques Bouchy. (Courtesy of CounterX Therapeutics)

ZB: So, this isn’t a cure for addiction, but a safety mechanism aimed at reducing the risk of fatal overdose?

JB: It’s a harm reduction strategy. If you’re familiar with HIV PrEP, think of it in that context (PrEP works by preventing the virus from establishing infection after exposure)

MP: We have preclinical data showing that CTRX-101 prevents respiratory depression, apnea, and bradycardia — the root causes of mortality associated with fentanyl. … We have also seen animals self-administer less fentanyl, [suggesting] it may also affect its rewarding and addictive properties. For example, the oxycodone vaccine trial (another opioid overdose prevention treatment) is still ongoing, and in vaccinated patients, you see decreased drug-liking scores, and people express that they are no longer interested in oxycodone.

ZB: How does that happen? 

MP: These antibodies act like a sponge that soaks up the drug, reducing … its entry into the brain. If you are vaccinated or have the monoclonal, and use fentanyl or another drug of choice, the effects are delayed. I always make the analogy that if you take a shot of bourbon … but over two hours [instead], it feels like Miller Lite. It’s less rewarding.

ZB: This could also protect people if they accidentally take drugs laced with fentanyl, I presume.

MP: Yes, that’s another aspect. Those who engage in drug use and are accidentally exposed to fentanyl would be prevented from dying. There are plenty of people who have been affected by fentanyl in a way that was difficult to predict. 

 I always make the analogy that if you take a shot of bourbon … but over two hours [instead], it feels like Miller Lite. It’s less rewarding.

JB: Up to 73 percent of counterfeit drugs have been adulterated with fentanyl. It’s pervasive in the drug supply. … Of the roughly 80 percent of the people who inject drugs and test positive for fentanyl, only about 20 percent are actually intending to take it. 

ZB: How novel is this approach of treating overdose with monoclonal antibodies or even vaccines?

MP: Vaccines and antibodies are novel in the sense that there has not been a commercial vaccine or antibody yet, but they’re not novel per se. In the 1970s, there was work on heroin vaccines in non-human primates, [including studies on] heroin self-administration. But this area of work has been moving forward in hiccups, depending upon federal government funding. In the late 1990s and early 2000s, there were clinical trials of cocaine and nicotine vaccines [that] reached Phase II and Phase III. But because there was evidence of efficacy only in the top responders, … these programs were halted.

ZB: Has it become harder to receive federal funding under the Trump administration?

MP: Yeah, the last two years have been particularly hard. For monoclonal antibodies, we are still fully supported by the NIH. But the vaccine pipeline has been hit hard. We have a fentanyl vaccine, and we lost funding for the Phase I clinical trial because of the current administration’s misalignment on vaccines. … Now we have a bunch of very expensive vials that are just sitting there, ready to go in somebody’s arm.

We have a fentanyl vaccine, and we lost funding for the Phase I clinical trial because of the current administration’s misalignment on vaccines. … Now we have a bunch of very expensive vials that are just sitting there, ready to go in somebody’s arm.

ZB: In the future, could these drugs be reformulated to treat other types of addiction?

MP: I’ve been making monoclonals against all sorts of drugs. It’s just a matter of what is closest to clinical trials. … If there’s a new drug on the streets, we can probably make a new antibody against it in a couple of weeks. Then the trick is raising enough money to actually accelerate development.

ZB: That makes sense. Would these treatments be safe if someone still needed to take opioids, for example, after surgery?

MP: That’s a very good question. The way we develop monoclonal antibodies and vaccines, we screen them for fentanyl and fentanyl-like compounds, but also for not binding off-target drugs. So, if you’re receiving a treatment against fentanyl, you can still take codeine, morphine, oxycodone for pain treatment and critical care. Monoclonal antibodies could be a game changer because they're safe, selective, and can also be combined. 

ZB: Could the availability of this lead people to take more fentanyl?

MP: We don’t believe so. … In any disease, you could [choose] not to take the drug and still engage in the behavior that led you there. But in animal studies, we don’t see that. We have animal studies where animals are self-administering fentanyl and when the monoclonal antibody is on board, they don’t try to overcome its effects. Somebody could potentially switch to other types of drugs [and] that’s quite difficult to control. That's also why we are … doing clinical trials to see whether this [holds true] in people.

JB: We think about … two or really three patient use cases. One is, someone ends up in the emergency department with an overdose. When they leave there, they are in a state of withdrawal and at a high risk … of a follow-up overdose. So that’s a place for CTRX-101 [as] it provides 30 days of protection from fentanyl. It can [prevent] a lethal overdose and keep them from returning to the emergency department. There’s a [clear] value proposition for patients and taxpayers. The other is patients in treatment and recovery programs, [who] are always at risk of relapse. CTRX-101 gives them protection from a fentanyl overdose. 

ZB: Is there something you wish people understood better about the fentanyl crisis?

MP: It is important to understand that the fentanyl crisis is everywhere. There is a false assumption that it is [confined to] the unhoused population. But in reality, … data shows that 84 percent of people with opioid use disorder have health insurance coverage, which means they probably have a job or a family. This could hit anybody. Think about other disorders like diabetes: no one will guilt anybody about their eating habits, or their genetics, or whatever led them there.

This is somebody’s daughter or son, their brother or sister. Everybody out there knows someone who has, in some way, been affected by the opioid crisis.

JB: Yeah, these patients sometimes just need an intervention to help push [them] back in the right direction. This is somebody’s daughter or son, their brother or sister. Everybody out there knows someone who has, in some way, been affected by the opioid crisis.

---