July marked a pivotal moment in the quest to combat the devastating impact of substance use disorders (SUD). The FDA gave the green light to a groundbreaking first-in-human clinical trial for a monoclonal antibody developed by Cessation Therapeutics, designed to prevent fentanyl overdoses. Simultaneously, Harm Reduction Therapeutics, a nonprofit biopharma, received FDA approval for an over-the-counter nasal spray formulation of naloxone—an indispensable tool in reversing opioid overdoses since its initial FDA nod in 1971.
These breakthroughs represent just the tip of the iceberg in a multifaceted effort to tackle the pervasive issue of substance use disorder. Presently, the National Institutes of Health’s clinical trial database boasts a staggering 714 active studies dedicated to exploring treatments for SUD.
Cessation CEO Tracy Woody emphasizes the urgency of the matter, stating, “You can’t treat a dead person. We are striving to keep these individuals alive and guide them towards comprehensive treatments.”
SUD is a relentless disease that reshapes a person’s brain and behavior, compelling them toward the uncontrollable consumption of harmful substances like alcohol, opioids, and illicit drugs. Shockingly, more than 40 million Americans aged 12 or older grappled with SUD in 2019, as reported by the Substance Abuse and Mental Health Services Administration. CDC data reveal a grim reality—over 150 lives are claimed daily by overdoses linked to synthetic opioids alone.
In this exploration, BioSpace delves into the innovative drug development endeavors poised to chip away at these heart-wrenching statistics.
Enter CSX-1004, the formidable creation by Cessation Therapeutics—a therapeutic innovation that stands as a beacon of hope in the fight against fentanyl-related fatalities. This groundbreaking solution works its magic by neutralizing fentanyl molecules the moment they venture into the bloodstream, preventing this deadly opioid from wreaking havoc in the brain and triggering an overdose. The result? A decisive halt to respiratory depression, the grim reaper of opioid overdoses.
Andy Barrett, the Chief Scientific Officer of Cessation Therapeutics, sheds light on their groundbreaking work, stating, “We’ve conducted extensive studies in nonhuman primates in collaboration with Harvard to assess fentanyl-induced respiratory depression. With this remarkable antibody, we demonstrated that a single dose could shield against fentanyl’s respiratory effects for an impressive 30 days.”
But there’s more to this game-changing therapy than meets the eye. Tracy Woody, CEO of Cessation Therapeutics, underscores the potential for broader accessibility. Unlike certain treatments for substance use disorder, like buprenorphine, which fall under the strict control of the Drug Enforcement Agency, monoclonal antibodies sidestep these regulatory barriers, paving the way for greater accessibility and hope in clinics.
Lowering Costs to Increase Accessibility
Meet RiVive, the game-changing over-the-counter therapeutic from Harm Reduction Therapeutics. This remarkable innovation functions as an opioid receptor antagonist, working in much the same way as the standard naloxone nasal sprays, previously accessible only via prescription. RiVive steps in as a guardian against overdose, swiftly binding to opioid receptors, effectively countering the effects of opioids and putting a halt to the deadly specter of respiratory depression.
In the past, obtaining naloxone—the key to saving lives during opioid overdoses—was far from straightforward, often requiring a prescription and a visit to a medical professional. Moreover, the price of this critical drug surged in lockstep with the opioid epidemic, presenting yet another hurdle. For instance, the cost of a vial of injectable naloxone from Hospira skyrocketed by a staggering 129% from 2014 to 2016, as reported in The New England Journal of Medicine.
Consider this: a two-pack of Narcan, a well-known naloxone brand, can set uninsured patients back a hefty $145, according to Naloxone Exchange. RiVive, on the other hand, is gearing up to make a life-saving difference at a fraction of the cost, offering a box with two doses for a mere $36. And that’s not all; 10% of this modest price tag is dedicated to a noble cause—providing free doses for those who may struggle to afford it. In partnership with Remedy Alliance, Harm Reduction Therapeutics plans to donate a staggering 200,000 naloxone doses for widespread distribution.
Michael Hufford, the visionary co-founder and CEO of Harm Reduction Therapeutics, emphasizes their mission: “Harm Reduction Therapeutics exists to fix a problem that, in an ideal market, wouldn’t exist. In an ideal market, the price of an old, established drug like naloxone should fall over time. It didn’t, so we helped correct that.” RiVive isn’t just changing the game; it’s rewriting the rules in favor of accessible, life-saving solutions for all.
Blocking the Cravings that Drive Addiction
Shifting their focus to another formidable foe in the realm of addiction, Addex Therapeutics and Indivior are setting their sights on curbing the very desire to consume alcohol.
The statistics are sobering: in the United States alone, approximately 14 million individuals grapple with a diagnosis of alcohol use disorder, and at the heart of this struggle lies the relentless issue of cravings. As Mark Crossley, CEO of Indivior, explains, “If we could intervene to reduce cravings, we believe there’s a chance to make a significant impact on alcohol consumption.”
Alcohol’s influence wreaks havoc on the brain’s GABA transmission, particularly targeting the GABAB receptor, a key player in the development and perpetuation of addiction. Robert Lütjens, Head of Discovery-Biology at Addex, highlights the extensive study of receptor agonists in the context of substance use. He notes that “agonists tested in preclinical models have demonstrated that GABAB receptor activation can effectively mitigate addiction and addictive behaviors.”
However, existing agonists like Baclofen come with a host of side effects, including sedation, and often necessitate higher doses due to tolerance buildup. To overcome these challenges, Addex and Indivior have embarked on a strategic partnership to develop GABAB-positive allosteric modulators (PAMs) designed specifically for tackling alcohol use disorder.
PAMs bring a new dimension to the fight against addiction. Unlike agonists, they step in to enhance GABAB receptor activity only when triggered by the GABA neurotransmitter. Mark Crossley elaborates, “In essence, PAMs work when the patient needs them, and the beauty of a PAM lies in its ability not to constantly occupy the receptor, effectively mitigating many of the side effects.”
The collaboration between these two pioneering companies is rapidly advancing. They anticipate having a lead asset from their GABAB PAM development program ready for clinical trials as early as the fourth quarter of 2023. In the quest to liberate individuals from the chains of alcohol addiction, Addex Therapeutics and Indivior are poised to make a profound difference.