Antibody to fight fentanyl overdose

The US president, Joe Biden, recently called his country’s fentanyl crisis an “American tragedy” and it is not hard to see why. The powerful drug contributed to 75,000 deaths in the United States last year…and there are concerns that the synthetic opioid could also soon wash up on European shores. In a bid to stop people from dying from fentanyl abuse, a company called Cessation Therapeutics has been developing novel antibody therapies designed to block the potent effects of the drug. The company’s chief scientific officer, Dr Andy Barrett, explains the dangers associated with fentanyl...

Andy - It's a highly potent opioid, and it's being made in clandestine labs, typically in Mexico, where the purity and potency of the fentanyl is not always known. So people who use the drug don't always know exactly how much they're using. And because even small changes in the dose of fentanyl can lead to toxicity and death, this creates a very dangerous environment for chronic drug use.

James - Currently, the best way to save someone who is overdosing on fentanyl is by administering Naloxone, commonly known by its trade name 'Narcan'. These canisters have been a real lifesaver, haven't they?

Andy - They absolutely have. Narcan is an indispensable medication that is widely available here in the United States and in other countries. Even with the widespread availability of Narcan, we continue to see an all time high of fentanyl related overdose deaths. One of the reasons is because it is very difficult to get to people fast enough to reverse fentanyl's effects. Fentanyl can produce life-threatening respiratory depression, or very slow breathing in a matter of two to three minutes, and it can be very difficult to get to people in time. Many drug users use drugs alone in their homes, and they're found the next morning. So we clearly need other strategies, preventative strategies, to prevent these overdoses from happening in the first place.

James - How have you worked to try and overcome the limitations of Narcan?

Andy - We're taking a novel approach. It's a paradigm shift in the management of overdoses. We're trying to prophylactically prevent these fentanyl related overdoses in high risk individuals who are already using opioids. So we're trying to administer a treatment, a monoclonal antibody that binds up fentanyl and prevents these overdoses from happening.

James - Let's dig in a little bit deeper into exactly how your new therapy works.

Andy - We have a monoclonal antibody that is targeted to fentanyl, and so if fentanyl is administered, it binds it up in the bloodstream, very avidly and prevents it from getting to the brain. Fentanyl getting to the brain is where it produces its problems. Fentanyl binds to the brainstem that's responsible for breathing and basically shuts that area down. The antibody again, prevents fentanyl, binds it up in the bloodstream, kind of pac-mans it up, and prevents those high concentrations in fentanyl from ever getting to the brain.

James - And the obvious advantage of your treatment as you've described it, is that it can be used in advance. How long does it offer protection from a fentanyl overdose for?

Andy - So we've shown in primate models that a single administration of the antibody can block potentially lethal doses of fentanyl for approximately a month, 28 days.

James - How much does it cost compared to Narcan?

Andy - We still have a lot of drug development to do. We haven't put a cost on it. Narcan is over the counter now, and so it is relatively cheap. However, we do think this can be priced in a manner that's commensurate with other once monthly products that are available for opioid use disorder. There are certain products that can contain a drug called buprenorphine that ameliorates withdrawal and craving symptoms, and we think it could be priced on par with those types of drugs.

James - Obviously, as vital as these treatments are towards saving lives of those with opioid dependency, there's still the need of course to grapple with the root causes of the current crisis, and they'll need to be addressed alongside this strategy.

Andy - So about five or six years ago, most of the fentanyl was coming from China, a lot of it via mail. There has been clamping down on raw materials there. What is happening is those raw materials are being shipped to Mexico where fentanyl is being manufactured in clandestine labs and then shipped to the United States via overland trafficking or sometimes in the mail. Some of those precursors are used in other chemicals that are important, so it's difficult to totally outlaw them with respect to variations in synthetic opioids over time and what could be next. Fentanyl is extremely easy to manufacture and it's extremely cheap. And drug users seem to really like its effects. It costs about 10% as much as heroin to produce. You don't need poppy fields, you don't need farmers as you would with heroin. You can make it in a tiny clandestine lab enough to make millions of dollars in a single batch. There have been reports of other synthetic opioids, but fentanyl still counts for the vast majority of the illicit drug supply. About 60% of all opioids that are seized contain fentanyl or structurally related fentanyl analogs for which our molecule would also work against.