In September, a police chief in Gloucester, MA, made news when he used social media to pressure companies that market prescription opidoids to consider their role in what has become a national crisis—opioid abuse and overdose-related deaths.
There were 24,500 opioid overdose-related deaths in 2013—attributable to both prescription opioids and heroin, according to the CDC. Because of efforts to curtail unnecessary opioid prescribing, the death rate from prescription opioid overdose has declined slightly in the last three years; however, heroin-related deaths quadrupled between 2002 and 2013.
The statistics are bleak. Even worse are the heartbreaking, personalized stories involving chronic pain, opioid addiction and unsuccessful efforts to save the people who end up dying after overdosing.
Last month, however, there was good news—news that has the potential to decrease the rate of opioid-related deaths.
An innovative delivery system changes everything
On November 18, the FDA approved Narcan (naloxone) nasal spray, which was developed by Lightlake Therapeutics and out-licensed to Adapt Pharma for commercialization. Naloxone, an opioid antagonist, is a medication that can stop or reverse the effects of opoid overdose.
Naloxone has been in use for 45 years, but until now has only been available as an injectable. Narcan nasal spray features a user-friendly, needle-free design, which makes it easier to use for saving lives. Undoubtedly, Narcan is on the holiday wish-list of every municipal police department, hospital emergency room, rehabilitation center and community-based clinic in the U.S.
The untapped potential of opioid antagonism
So why did it take so long to get an FDA-approved nasal spray version of naloxone? “Opioid antagonists have been around for several decades, but have been underutilized. Their full potential has not been developed, “Lightlake CEO, Roger Crystal, told Biopharma Dive.
When Crystal, a trained ENT surgeon, came to Lightlake in 2009, he was attracted to the focus on unmet medical needs in addiction, and the ability to use his nasal therapeutic experience to help develop a product with a “compelling safety profile.”
In 2013, Lightlake entered into a public-private partnership with the National Institute on Drug Abuse (NIDA) to develop nalaxone nasal spray. Clinical trials started that fall, and shortly thereafter Lightlake received fast track designation and priority review from the FDA.
“We made sure that we knew which questions to ask in order to get the advice we needed to move forward quickly. It’s important to understand the area you’re entering. We took a very clinical approach. We had opioid experience and advisors in place to optimize the nasal spray formulation,” said Crystal.
In December 2014, after late-stage clinical trials were completed, the company entered into a licensing agreement with Adapt Pharma in a deal worth up to $55 million, not including royalties, for Lightlake.
There was definitely a sense of urgency surrounding the development of this product. It took a total of three years to develop and gain approval for Narcan, something that was possible because of the close collaboration between Lightlake and NIDA, and the commercialization support provided by Adapt Pharma. The original PDUFA date, which was supposed to be January 2016, has now become the launch date for Narcan.
Competition across the pond
Innovation tends to come in waves, and when an idea gains traction, it often gives rise to more competition. Such was the case with the development of naloxone nasal spray. Less than a week after Narcan was approved, Invidior, a U.K.-based company, received a Complete Response Letter for its formulation of intranasal naloxone.
The main problem with Invidior’s formulation was one of clinical pharmacology. Specifically early-stage uptake of Invidior’s nasal spray was not equivalent to the reference product (0.4 mg naloxone by intramuscular injection).
Fortunately for Lightlake, one of the main areas of focus for the scientific team at NIDA was to design and conduct the clinical trials required to determine that Narcan delivered naloxone as quickly and effectively as the injectable. The collaboration between NIDA and Lightlake proved critical to the success of the submission.
Binge eating disorder
Although Narcan is a fait accompli, Lightlake is focusing on developing formulations of nalaxone for other addictive disorders, including binge eating disorder (BED) and cocaine addiction. Crystal explained, “The opioid system is key in addiction. Being able to block that system in a way that is safe, well-tolerated and effective is the key to addressing several disorders.”
In Lightlake’s phase 2, randomized, double-blind, placebo-controlled, six-month BED trial, 127 patients were randomized to either naloxone or placebo. Patients who used naloxone spent significantly less time binge-eating, compared with patients who received placebo (84 minutes vs. 125 minutes). Naloxone also led to significant decreases in BMI over the six-month period.
When Shire’s Vyvanse (lisdexamfetamine) was approved for the treatment of BED in February, it brought the issue of BED to the forefront as a scientific issue—not a moral issue. That’s an important part of addressing any addiction, according to Crystal.
“The big challenge that we are currently addressing is establishing a credible and biological explanation for why people have a disease. Shire has already done a lot of the heavy lifting for us in terms of BED awareness.”
One of the most interesting things about the way nalaxone works is that it is taken on an as-needed basis. It works on the spot, but also gradually reduces a person’s desire to binge-eat, according to Crystal. “We use a symptom-driven approach. The goal is to provide medication at that point in time when a person wants to binge. The nasal spray acts on the brain in minutes, but because of as-needed dosing, patients don’t have naloxone in their bodies when they don’t need it.”
Crystal is not sure how Lightlake will commercialize naloxone for BED. “We may launch it ourselves,” he said. “And we may also consider the role of our drug in combination with other therapies for BED.”
Many stakeholders, one goal
Just as necessity is the mother of invention, an urgent unmet medical need is the foundation for groundbreaking innovation. There continues to be a great need for more scientific approaches to addressing addiction.
“We are privileged that some of the world’s leading experts on addiction have given us feedback. These experts, along with patients, addiction-support groups, government agencies and other pharmaceutical companies are all part of this innovative process. That’s why it works,” said Crystal.