This is a recurring column on clinical research in the early stages of development, what is referred to as phase 1. These are treatments that are being used for the first time in a small number of human patients to determine safety, dosing and general pharmacological activity.
Amid the opioid crisis, an epidemic that kills more than 130 Americans every day, researchers are seeking a vaccine that could render a patient immune to the addictive properties of the potent painkillers.
The National Institutes of Health solicited proposals for the clinical development of vaccines that could prevent the passage of opioids into the brain in a March 2019 broad agency announcement.
According to Roosevelt University assistant professor of medicinal chemistry Margaret Olson, an opioid vaccine would provide another tool in "the arsenal we have to fight against the opioid crisis." Opioid drugs include the illegal drug heroin as well as prescription medicines like oxycodone and morphine.
Vaccines for addiction are developed first by characterizing the chemical structure of the drug, and then linking a chemical piece within the structure called the hapten to an immunogenic carrier protein, which stimulates immune response. When injected into the body, the immune system recognizes the drug as foreign, and the body makes antibodies that will find the drug and prevent it from reaching the brain.
"These types of vaccines would really help individuals not fall down the same addiction spiral again," Olson said.
The vaccines would likely require boosters or revaccinations over the course of weeks or months, Olson added.
Olson — who has previously worked with the "pioneer" of vaccines for drugs of abuse, The Scripps Research Institute's Kim Janda — said opioid vaccine trials differ only slightly from those held for more typical vaccines against infectious agents, like flu and tetanus.
"You would very much want a patient who has this interest in quitting and breaking their addiction; you want to work together," Olson said. Individuals could potentially take a large dose of drugs and overcome the vaccine if they still wanted to achieve the high associated with opioids.
Cessation Therapeutics is developing an opioid vaccine licensed from Scripps' Janda. The company's research and development director Paul Bremer confirmed the fairly typical makeup for the therapy's trial.
Though vaccines targeting addictive drugs date back to the 1970s, the failure of cocaine vaccines in clinical trials may have scared researchers off for a time, Olson said.
Cocaine vaccines were furthest in development, and some, like Columbia University's Ronald Crystal, are still plugging away in the space. But the opioid crisis has spurred laboratories in another direction, Olson said.
"That has pushed many of the players in the cocaine vaccine field toward opioids just because it's a bigger problem to answer," Olson said.
The NIH has granted the Walter Reed Army Institute of Research resources to push its experimental heroin vaccine through phase 1/2a clinical trials, as well as to begin developing a fentanyl vaccine, the WRAIR said in an October 2018 release.
The vaccine, also licensed to Narcan-maker Opiant Pharmaceuticals Inc., could potentially be used with other approved opioid use disorder medications, such as Indivior PLC's Suboxone, or buprenorphine, Opiant said.
The heroin vaccine will first undergo safety testing, and phase 1 trial testing efficacy is slated for fall 2020.
The New York State Psychiatric Institute's Research Foundation for Mental Hygiene also received grants from the NIH in August 2019 for its bivalent opioid vaccine, which would target both oxycodone and heroin.
The researchers will study the oxycodone and heroin vaccines separately in phase 1a/1b studies for safety and preliminary efficacy, before developing the bivalent vaccine candidate. The studies will recruit individuals diagnosed with opioid use disorder, the project abstract said.
Academics take charge
Not lost on researchers such as Olson and Janda is the absence of large pharmaceutical companies — particularly those who market opioid drugs — investing in opioid vaccines. The researchers noted the absence in a December 2017 article published in EMBO Reports.
The vaccine would need to generate a certain amount of revenue to make the investment worth it, Olson told S&P Global Market Intelligence.
"It's very cold, I don't like it at all, but these companies work based off of a cost-benefit analysis," Olson explained. "Substance use disorder affects [individuals'] operating ability in normal society — whether they can hold a job for long periods of time, whether they have financial means … It's a unique situation that we don't commonly see in the drug development field."