The inventor and developer of the NARCAN® Nasal Spray talks about the opioid crisis, fentanyl, and what he hopes to hear discussed at this week’s virtual RX Drug and Heroin Summit.

Roger Crystal set out to impact healthcare at a ‘societal’ level. The doctor who developed the NARCAN® Nasal Spray says he is proud to see its impact on the opioid crisis in the United States: the opioid overdose reversal medicine has saved a large number of lives.

Now, as Opiant develops a potential new standard in opioid overdose reversal medicine designed to tackle synthetic opioids like fentanyl, the President and CEO of Opiant Pharmaceuticals says he could never of envisaged the opioid crisis would be dominated by such a dangerous compound.

“Fentanyl is really a different beast. It is far deadlier than either heroin or prescription opioids.”

Ahead of this year’s RX Drug and Heroin Summit, Dr. Crystal spoke with Opiant’s Communications Vice President Ben Atkins on April 7. What follows is an edited transcript of the conversation

Q: Why did you develop the NARCAN® Nasal Spray?
A: Roger Crystal: I developed the NARCAN® Nasal Spray because data in 2011 made quite apparent an emerging opioid crisis in the United States and that this was going to become a serious problem. We were already observing more opioid overdose deaths in the United States than there were road traffic accident deaths. And one of the main limitations was the fact that naloxone, a medication for reversing opioid overdose, was only approved by the FDA as an injection. In this form, the only people qualified to use it to save a life were well-trained paramedics or physicians. As a nasal spray, it can be put into the hands of anyone, enabling them to use it to save a life.

Q: How would you characterize the opioid situation today?
A: Roger Crystal: The opioid crisis today, and in particular for those individuals with an opioid use disorder, has become a fentanyl crisis. Fentanyl is really a different beast. It’s far deadlier than either heroin or prescription opioids. Fentanyl is a synthetic opioid that is at least 50 times stronger than heroin. It acts quicker and lasts longer than heroin. It’s also easier and cheaper to make than heroin. The real problem here is that many people don’t set out to take fentanyl. It is often hidden in fake prescription medicines and in illicit drugs including cocaine and heroin. The consequences are terrible. Fentanyl was involved in over 60% of the almost 50,000 opioid overdose deaths suffered in the United States in 2018 – a ten percent increase in deaths from synthetic opioids since the previous year.

Q. Are U.S. stakeholders paying enough attention to fentanyl?
A: Roger Crystal: Our concern about fentanyl is shared by experts in our field such as the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health. The U.S. Surgeon General has cited opioids as being a major threat to the continued health of the nation and has encouraged widespread use of naloxone to help save lives. In addition, carfentanil, another synthetic opioid, even stronger than heroin, was used in a chemical attack in Russia, in 2002, resulting in the deaths of over 100 people. BARDA, the U.S. government agency responsible for developing counter measures against biological and chemical attacks, therefore sees the potential risk of a fentanyl chemical attack here in the United States. I believe deaths can be avoided if we recognize the scope of the fentanyl problem, act early and comprehensively, and enable scientific and medical advancement in our understanding and treatment of opioid use disorders and overdose.

Q: What steps do you see in the United States making a difference against opioid deaths?
A: Roger Crystal: I find it unacceptable that we still have almost 50,000 opiate overdose deaths a year in this country. We are losing people, young people, people with families. One way we can effectively reduce the incidence of these opioid overdose deaths is to think about who’s at higher risk of an overdose. We’re seeing some action there already with co-prescribing. In this situation, for patients considered at higher risk of an opioid overdose, yet an opioid is deemed the most suitable analgesic for their pain, the safest practice would be to co-prescribe an opioid overdose reversal agent. Having help at hand and being proactive is, I think, one of the most effective measures. There are now nine states who have some form of mandatory co-prescribing laws and we expect more to follow this year.

Q: Do you see a particular state establishing a model for the rest of the country?
A: Roger Crystal: Of the nine states to have introduced mandatory co-prescribing, New Mexico probably takes the most responsible position. It’s interesting because it goes beyond current CDC guidelines. New Mexico’s new law says that anyone who is prescribed an opioid for five days or longer should be co-prescribed a reversal agent. It doesn’t factor in the patient’s prior medical conditions, their background use of opioids or anything of that nature. It simply says if you’re taking an opioid for five days or more, you receive a prescription for the antidote. Take me, as an example. I’m in good medical condition. I’ve not got a history of opioid abuse. However, let’s say I was to have knee surgery and require an opioid for the pain. There’s still a risk that I can overdose. So, from my perspective, New Mexico’s position has the greatest potential to save lives.

Q: What can you tell us about OPNT003?
A: Roger Crystal: OPNT003 is an opioid overdose reversal agent in development by Opiant Pharmaceuticals. We believe 003 is well suited to address overdoses from fentanyl and other more powerful synthetic opioids. The main molecule in OPNT003, is nalmefene. We believe it has better ‘punching power’ than naloxone. First, is its inherent potency. It’s been shown to have a five times or greater affinity at the mu opioid receptor than naloxone, so it binds tighter. Second, is has a fast onset of action. A third feature is the potential for longer action based on its longer half-life. That’s important because naloxone has a shorter half-life than fentanyl, so in an overdose there is a risk that the fentanyl kicks in again, as the naloxone wears off. So, someone can fall back into an opioid overdose. We are developing OPNT003 as a nasal spray. So, similar to the NARCAN® Nasal Spray, so it also has the potential to be used by anyone very easily.

Q: What about tackling the Opioid Use Disorder itself. What can be done there?
A: Roger Crystal: As we think about how we address opioid addiction, as a nation, we must approach treating this as a chronic medical disease. It is a chronic brain disease, and this needs to be broadly recognized, and treated as such, in the same way diabetes, multiple sclerosis and rheumatoid arthritis are managed. In these chronic illnesses, there is a multidisciplinary coordinated approach that reduces disease severity and relapse prevention. Key to this is medication. And the same approach should be standard for OUD. There’s extensive data that show that if patients start on suitable medical treatment for OUD and remain on that medicine, then their outcomes are far better. And when I say outcomes, I refer to relapse prevention and establishing long term recovery. We really need to provide better access to and use of this medication.

Methadone and buprenorphine are both opioids and therefore considered substitution therapy, used to suppress a patient’s cravings and withdrawal yet without the same euphoric effects. The opioid antagonist naltrexone, given as a monthly depot injection, is another form of treating OUD. Instead of controlling withdrawal and cravings, it treats OUD by blocking the mu opioid receptors so that the opioid that one might try, and take, doesn’t cause any effect. Opioid antagonists are less commonly used than the substitution therapy, yet it’s a compelling way of treating OUD, especially if the patient prefers to be off opioids entirely.

Q: When and how does our opioid problem end here in the U.S.?
A: Roger Crystal: OUD is a chronic brain disease and because of this, I believe there will always be patients who will chronically misuse opioids. Now can we control that? Yes, I think we can in two ways. First, we can control it by reducing its incidence – reducing the number of patients who have a new diagnosis of OUD. But unfortunately, like any other chronic condition, once you have it, you really do have it for life. A bit like diabetes or multiple sclerosis, for example. So, second, we need better treatments that we can use to control the severity of disease. And that’s what we’re committed to: to go beyond just the overdose issue and seek to contribute towards the tools available to physicians to better treat this condition. Then, our opioid epidemic and this fentanyl crisis, can be better addressed in the future.

Q: What do you hope to hear from stakeholders at the RX Drug and Heroin Summit this week?
A: Roger Crystal: First, I would really like to see stakeholders recognize that OUD is a chronic brain disease that needs medical treatment. Second, understanding that we’re dealing with a chronic medical disease, we need to continuously invest in developing new medicines and bringing them to the front line. I am pleased to see the term Medication Assisted Treatment replaced with Medications for Addiction Treatment. I found the old terminology such a disappointing description for an intervention that has the most proven benefit, because it sounds almost like it’s a supplementary type of offering for a patient with OUD. The reason for this is simple: using the analogy of type 1 diabetes, can you imagine if we said to a patient ‘we’re going to give you some patient education, we’re going to make sure that your feet are well tended (because diabetic foot ulcers are a big issue); we are going to give you some time with the diabetes specialist nurse to give you dietary advice. Oh, and by the way, we’re going to give you some insulin as well.’ Of course, we don’t say that; and instead we recognize that insulin is the most critical part of their treatment. But that’s the analogy with our current approach to OUD. So, I think changing that around, so medicine leads in our treatment of OUD, is key. Third, I would like to see all stakeholders see this is now a fentanyl issue. It’s getting worse – much worse. But we can attack it now. Let’s not wait for the numbers to trickle through.