When pop star Demi Lovato experienced an apparent opioid-related overdose last summer, reports stated that she was saved by a medication called NARCAN® Nasal Spray — the first FDA-approved nasal form of naloxone, an opioid antagonist.
The company that developed NARCAN® Nasal Spray is Opiant Pharmaceuticals, based in Santa Monica, CA. CEO Dr. Roger Crystal will be a headliner at the upcoming BIO CEO & Investor Conference, leading a fireside chat at noon on Tuesday, February 12.
Dr. Crystal’s Personal Story
Dr. Crystal began his career as an ear, nose and throat surgeon in the United Kingdom. From the outset, he was driven to make an impact in health care at a population level, as opposed to the individual doctor/patient relationship. He did his medical training at the University of Birmingham and soon after moved to London.
The London bomb attack in 2005 left a lasting impression on him. “We were one of the main hospitals treating all of the casualties,” he noted. “Even in times like that, the sickest patients in the hospital, apart from the casualties, were the patients who were heroin addicts who had gotten themselves into terrible complications requiring surgical interventions because of their underlying addiction. The harm that they would put themselves in... those patients were in the back of my mind when I thought about what I was looking to do.”
It was during that time Crystal determined he would go beyond his medical education and study at the London Business School. Armed with his MBA, he held roles in finance, management consulting and worked at GE Healthcare. But he never lost sight of his initial goal of serving the most challenged populations. Today, he leads a company addressing one of the most pressing issues of our time: addictions and drug overdose.
Opiant’s Overdose Treatment Pipeline
Crystal and his company, Opiant (previously called Lightlake Therapeutics), initially studied nasal naloxone for the treatment of Binge Eating Disorder, which is thought to block the reward patients get from the release of endorphins resulting from the over-consumption of food high in sugar, fat or salt. But given the number of opioid overdoses, the company refocused its efforts to develop a user-friendly nasal naloxone spray, which was approved in 2015.
“In 2011, there were more opioid-related deaths in the United States than there were traffic accidents,” Crystal recalled. “We thought, hold on, are we missing a trick here? Why aren't we taking naloxone back to its roots and developing an FDA-approved naloxone nasal spray to reverse opioid overdose?”
Naloxone works by restoring breathing. In addition to acting on the reward center in the brain, opioids also act on the brain’s breathing center. During an opioid overdose, the body’s automatic drive to breath gets eliminated. Naloxone binds to the opioid receptor and blocks the effects of the opioid to reverse the overdose.
The drug has saved countless lives. However, the flood of fentanyl into the market presents new challenges. Naloxone lasts for about an hour and a half, whereas the effects of fentanyl might last as long as seven hours. If a person has overdosed on fentanyl, they may be revived with naloxone only to slip back into an overdose when it wears off. Recognizing this urgent need, Opiant is now working on a new nasal spray using a molecule called nalmefene.
“Nalmefene is another opioid antagonist and similar to naloxone,” Crystal says. “However, it binds tighter to the opioid receptor compared to naloxone and has a longer half-life. Naloxone’s half-life is about an hour and a half, which is similar to heroin. So before we had this fentanyl issue, naloxone was well-matched to the half-life of heroin. But fentanyl has a half-life of seven to eight hours, so there’s a potential issue where patients can fall back into an overdose once the naloxone’s worn off. This seems to be what happened with Prince who was initially resuscitated when he overdosed on what turned out to be fentanyl, but essentially died because the fentanyl kind of kicked in again.”
Nalmefene Draws Attention from HHS
In 2017, 55 percent of overdose deaths contained fentanyl. With the onslaught of fentanyl into the illicit drug market, there is concern among national security experts that its abundance could make weaponization a real possibility.
Last year, 50 kilograms of fentanyl were seized in Nebraska — enough to kill 26 million people. There is precedent for weaponization of the substance. The gas used by Russia to suppress the Moscow theater hostage crisis in 2002 was made with a fentanyl derivative and is said to have killed between 117 and 130 people.
That is why the Biomedical Advanced Research and Development Authority — the U.S. Department of Health and Human Services agency charged with protecting the nation from chemical and biological threats — is partnering with Opiant to support the development of its nasal nalmefene. The company is targeting filing for FDA approval in 2020.
Other Products in the Pipeline
Resuscitating someone from an opioid overdose is only half the battle, Crystal notes. Addressing the underlying addiction is equally important or more overdoses could potentially follow. Opiant is working on developing products to do just that.
“Treating the overdose is, of course imperative, but as a company, we want to treat the underlying addiction as well,” Crystal says. “Our pipeline includes a heroin vaccine, as well as a naltrexone nasal spray to treat alcohol use disorder.”
Crystal will discuss innovative breakthroughs in the fight to curb the opioid epidemic at the BIO CEO & Investor Conference in New York. To hear him and other industry leaders on the cusp of medical breakthroughs, register to attend here.
For a comprehensive look at efforts to fight the opioid crisis, see BIO’s Advocate toolkit.