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While opioids (e.g., oxycodone, fentanyl) are widely prescribed for acute pain relief, they are often abused due to their highly addictive nature. More than 60% of drug overdose deaths involve an opioid. With total mortality having quadrupled since 2005, more deaths are now attributable to opioids than to road accidents.
“Nearly 450,000 people died from overdoses involving any opioid … from 1999-2018.”
– Centers for Disease Control and Prevention
The misuse of prescription opioids costs the United States nearly $80 billion per year, including the costs of healthcare, lost productivity, addiction treatment, and criminal justice involvement.1
There is a widely recognized, urgent need for a safer, non-addictive pain-killer for peri-operative pain.
The over-prescription of opioids is being driven largely by the lack of alternative therapies that are both safe and effective. Of the 50 million US surgical patients requiring post-operative pain medication each year2, 80% are prescribed opioids3, with more than 6% becoming persistent opioid users after surgery.4 In targeting the $11 billion market for post-surgical pain relief5, ATB-352 represents a compelling therapy given its analgesic potency, gastrointestinal safety and lack of abuse potential.
Many surgeries require a multi-day hospital recovery period, during which intravenous agents are often prescribed to manage peri-operative pain. Upon discharge from hospital care, patients may continue to suffer from pain for several weeks. This transition can be challenging for both patients and physicians, who seek to prescribe an oral therapeutic that is effective but does not create addiction concerns. To address this, Antibe has adopted a two-stage product strategy to streamline pain management and to avoid changing medications during the recovery period:
(i) an aqueous formulation of ATB-352 for intravenous administration of ATB-352 while in hospital; and
(ii) a oral tablet formulation of ATB-352 for patient use following hospital discharge.
In preclinical studies, ATB-352 caused negligible intestinal damage compared to ketoprofen, despite comparable suppression of intestinal prostaglandin or whole blood thromboxane synthesis.6 The rats were treated orally twice-daily for 5 days with either 10 mg/kg ketoprofen, or an equimolar dose of ATB-352 (14.5 mg/kg). Pharmacokinetic and toxicology studies suggest that ATB-352, like ATB-346, is effective when administered once daily.7
When tested over a concentration range of 3 to 30 µg/mL in a CEREP in vitro assay, no agonist effect of ATB-352 was found against the µ(MOP) opioid receptor, indicating no addiction potential.7
In early 2020, the results of a series of studies were published demonstrating that ATB-352 induces significantly more potent and effective analgesia than ketoprofen in a well characterized animal model of surgical pain.8 Despite the increased pain reduction, ATB-352 was also much better tolerated in the GI tract; mice receiving ketoprofen exhibited a dose-dependent increase in the severity of bleeding ulcers in the stomach and intestine. In contrast, no GI damage was observed in mice treated with ATB-352, even at very high doses.8
A mechanism of action was also identified that explains the increased pain-killing effects. In addition to blocking the production of pain-promoting prostaglandins, ATB-352 further reduced pain by significantly elevating levels of naturally occurring endocannabinoids in comparison to the levels of endocannabinoids observed in mice treated with ketoprofen.8
1) Florence et al. The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013. Med Care. 2016;54(10):901-906.
(2) Transparency Market Research: “Post-Operative Pain Market: Overview”, 2016.
(3) Hill MV et al. Wide variation and excessive dosage of opioid prescriptions for common general surgical procedures. Ann Surg. 2017;265(4):709-714.
(4) Brummett CM et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6).
(5) Transparency Market Research: “Postoperative Pain Therapeutics Market – Global Industry Analysis, Size, Share, Growth, Trends,
and Forecast, 2019–2027″, 2018.
(6) Gemici et al. H2S-releasing drugs: anti-inflammatory, cytoprotective and chemopreventative potential. Nitric Oxide. 2015 Apr 30;46:25-31.
(7) Antibe pre-clinical data on ATB-352.
(8) Costa et al. Enhanced Analgesic Effects and GI Safety of A Novel Hydrogen Sulfide-Releasing Anti- Inflammatory Drug (ATB-352): A Role for Endogenous Cannabinoids. Antioxidant and Redox Signaling. 2020 Feb 16.
9) National Center on Health Statistics, CDC Wonder.