As access and use of its NARCAN Nasal Spray for opioid overdose continue to grow, Opiant Pharmaceuticals’ (NASDAQ:OPNT) core focus remains on the development of nasal opioid antagonists for chronic addictions, such as alcohol use disorder (AUD) and bulimia nervosa (BN).
“Addiction is now recognized as a brain disease, yet only one-in-nine addicts is receiving appropriate treatment,” CEO, Dr. Roger Crystal, says in an interview with BioTuesdays. “Going forward, pharmacotherapy should represent a minimum standard-of-care for opioid use disorder (OUD).”
In addition to its own pipeline, Opiant is collaborating with Titan Pharmaceuticals (NASDAQ:TTNP) to explore development of a six-month implant to prevent opioid relapse and overdose in patients with OUD.
“We know that the longer OUD patients are on medical treatment, the far more likely they are to have better long-term outcomes in terms of recovery and reduction in relapse,” Dr. Crystal says. “An opioid antagonist implant of six months duration represents a significant advancement in treatment for this patient population.”
Opiant also has a heroin vaccine in preclinical development, but Dr. Crystal points out that while the product is compelling, “it’s not for tomorrow” and a six-month implant has the potential for a much faster development program.
Dr. Crystal explains that addiction is driven by the brain’s reward center releasing dopamine. Opioids flood the brain with dopamine, leading to misuse and abuse. Opioid antagonists, on the other hand, bind to opiate receptors that modulate and normalize dopamine release. As a result, the feelings of pleasure produced by these substances are blocked.
“The advantage of a nasal spray is that it opens the patient population to millions of individuals seeking a better medical treatment than what’s currently offered, so the markets are massive,” he adds.
For example, he points out that the use of injectable naloxone (the medication delivered in NARCAN Nasal Spray, the only FDA-approved nasal naloxone formulation) for opioid overdose is limited to trained personnel, while naloxone delivered as a nasal spray can be used by anyone and can even be co-prescribed alongside opioid painkiller prescriptions – an approach taken by states like Virginia and Vermont, which are now mandating prescribing of naloxone for patients considered at high-risk for opioid overdose.
Leading medical authorities, including the American Medical Association and Centers for Disease Control and Prevention, also recommend co-prescribing.
“If you’re a parent of a teen, who you find in your home unresponsive, using a nasal spray is more intuitive for a non-medically trained person, and therefore a far more attractive route of administration, especially when every second counts,” Dr. Crystal contends.
“Co-prescribing naloxone alongside opioids not only helps reduce the risk of overdose with that prescription, but also places a layperson-friendly naloxone in cabinets and homes across America, providing an on-site, in-home emergency response for overdose caused by any opioid, including heroin and fentanyl,” he adds.
“Not only is NARCAN Nasal Spray an easy-to-use use form of naloxone for opioid overdose, it is also needle-free and among the least expensive of available alternatives, such as injectable naloxone, auto injectors and improvised nasal kits,” according to Dr. Crystal.
“NARCAN appears to be the mainstream opioid overdose rescue product across the U.S.,” he adds, especially among first responder organizations such as the police, who are often the first at the scene of an opioid overdose.
Opiant’s NARCAN Nasal Spray is the only FDA-approved naloxone nasal spray for the reversal of opioid overdose. Opiant licensed NARCAN to Adapt Pharma in 2014 and the FDA approved NARCAN in 2015. NARCAN, which has seven FDA Orange Book-listed patents, is also cleared for sale in Canada.
Dr. Crystal points out that based on the licensing agreement with Adapt Pharma, if net sales of NARCAN Nasal Spray hit $75-million for all of 2017, Opiant again should receive royalty and milestone payments from Adapt Pharma in 2018.
In December 2016, Opiant signed a partial royalty monetization deal for NARCAN with SWK Holdings for up to $17.5-million, including a payment of $3.75-million in the third quarter of 2017, which was triggered by NARCAN’s net sales topping $25-million in the first half.
Dr. Crystal says nasal naltrexone (a short-acting opiate and alcohol blocking agent) has the potential to help the 2.2 million patients with AUD who are seeking treatment. Currently, the majority of this population does not take medication because of barriers such as requiring prior detoxification, fear of severe withdrawal symptoms, medication side effects and limited efficacy, he adds.
In its AUD program, Opiant has obtained Phase 1 data for OPNT002, nasal naltrexone. The company has an ongoing development underway for the product, including formulation and aiming to undertake further clinical trials in 2018.
Opiant is pursuing a 505(b)(2) regulatory pathway for OPNT002, which should speed FDA approval, compared to the development costs and timelines associated with the FDA’s review of a new chemical entity.
According to Dr. Crystal, there are nearly 16 million individuals in the U.S. that meet the criteria of AUD, of which 2.2 million are seeking treatment, but only 400,000 receiving pharmacotherapy. “AUD is a massive population with unmet medical needs.”
Dr. Crystal explains that drinking alcohol causes the release of endorphins, which are the body’s endogenous opioids, in the reward center of the brain. Naltrexone, an opioid antagonist, blocks the effects of these endorphins, reducing the downstream release of dopamine so that “patients reduce heavy drinking by blocking the endorphin reward.”
He adds that most existing pharmacotherapies for AUD typically require abstinence prior to beginning medication, so many patients are unwilling to go down this route. For those who choose to take existing medication, he says the drugs are poorly tolerated with limited efficacy so adherence is low.
“The advantage of our OPNT002 nasal spray is that we do not expect prior abstinence and therefore withdrawal, allowing patients to take the nasal spray whenever they have the urge to drink, potentially providing greater control over drinking,” he contends.
With Opiant’s nasal formulation, naltrexone also has the potential to promote fast absorption into the body, compared with the oral medication, Dr. Crystal points out.
The FDA now accepts harm reduction or a reduction in heavy drinking, not abstinence, as an acceptable outcome measure for AUD medications. “With AUD on the rise, this presents an attractive commercial opportunity,” he adds.
Dr. Crystal also points out that there are 2.5 million patients with BN in the U.S., of which 45% are receiving treatment with fluoxetine, but experiencing poor response rates to the medication.
Like alcohol, calorie-dense foods such as those consumed during a typical binge episode, also release endorphins. OPNT001 blocks the effects of these endorphins, so that consuming large quantities of calorie dense foods are no longer rewarding.
In its program for eating disorders, Opiant’s nasal opioid antagonist spray, OPNT001, is being tested in a Phase 2 placebo-controlled study with 80 patients suffering from BN. The primary endpoint for this study, which is being conducted in the UK, is a reduction in binge eating days and a data readout is slated for the second/third quarter of 2018.
In binge eating disorder (BED), a related condition, an earlier proof-of-concept study conducted in Helsinki, OPNT001 demonstrated a significant reduction from baseline bingeing after six months, compared with placebo.
Although eating disorders affect millions of people, Dr. Crystal says there is only one drug approved for each indication: fluoxetine for BN and Shire’s Vyvanse for BED.
“As with our other nasal spray programs, we have the potential of improved compliance with on-demand dosing for these conditions,” he adds.