CONCORD, Mass.--(BUSINESS WIRE)--Tremeau Pharmaceuticals today announced that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. Patent Application No. 17/240,446. Once issued, the patent will provide composition of matter patent protection for Tremeau’s novel deuterium-enriched etoricoxib compound, TRM-362 (d3-etoricoxib), through at least April 2041.
Etoricoxib is a highly selective cyclooxygenase-2 (COX-2) non-steroidal anti-inflammatory drug (NSAID) with a well-established benefit/risk profile. It has demonstrated efficacy and tolerability superior to opioids in select acute pain conditions1,2 with an onset of action in as early as 24 minutes, and has no effect on platelet aggregation.3 It is broadly available outside of the U.S.
In in vitro and animal studies, the pharmacokinetic profile of TRM-362 was highly differentiated from non-enriched etoricoxib, including achieving a 50% greater Cmax and a 50% higher exposure at an equivalent dose in a nonclinical cross-over study in dogs. These studies suggest that TRM-362 could provide similar or greater acute pain efficacy when compared to non-enriched etoricoxib, potentially at a lower dose.
Tremeau has gained formal feedback from FDA regarding the clinical and regulatory requirements to develop a COX-2 selective NSAID for acute pain conditions, and plans to rapidly advance TRM-362 as an opioid alternative for this indication. Tremeau believes that TRM-362 could serve as a powerful non-opioid pain product for patients in whom an increased risk of bleeding is a concern, such as those in the post-operative setting.
“Post-operative bleeding is a significant concern after surgery, and must be balanced with adequate pain management and DVT prophylaxis,” said Michael M. Alexiades, MD, Professor of Clinical Orthopaedic Surgery, Weill Cornell Medical College and Director, Department of Rehabilitation, Hospital for Special Surgery, New York City, NY. “The surgical community would welcome a more potent non-opioid pain medication that does not carry the bleeding risk of traditional NSAIDs.”
“Despite the significant and continuing unmet need for non-opioid pain medications, there has been little development of viable opioid alternatives. Based on etoricoxib’s well-known safety and efficacy profile and our preclinical studies to date, we believe that TRM-362 has the potential to be a best-in-class non-opioid treatment option for patients with acute pain,” said Bradford C. Sippy, Tremeau’s Chief Executive Officer. “A major design flaw of previous COX-2 selective NSAIDs and current opioid products is the easy, chronic access to doses intended only for acute use. We will work proactively with FDA to design a product for acute pain that ensures access only for short-term use.”
About TRM-362 (Deuterated Etoricoxib)
TRM-362 is an investigational non-opioid pain treatment containing deuterated etoricoxib. Marketed outside of the U.S. as ARCOXIA, etoricoxib was shown to be a highly potent cyclooxygenase-2 selective NSAID, with a well-established efficacy profile. Etoricoxib was shown to have no effect on bleeding time and has demonstrated a reduced risk of gastrointestinal bleeding versus a traditional NSAID in controlled trials.3
Deuterium is a naturally occurring, stable isotope of hydrogen, with an additional neutron in its nucleus. Selectively substituting hydrogen with deuterium, or deuteration, may alter a molecule’s metabolic profile while maintaining its core pharmacodynamic characteristics. Deuteration has been successfully leveraged in several approved and/or late-stage pharmaceutical products.
It has been demonstrated in multiple, often industry-independent studies that cardiovascular safety is a dose- and duration-dependent risk of all NSAIDs.4-9 NSAIDs, including etoricoxib, cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. NSAIDs, including etoricoxib, are contraindicated in the setting of coronary artery bypass graft. NSAIDs, including etoricoxib, cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding are at greater risk for serious gastrointestinal events.
About Tremeau Pharmaceuticals
Tremeau is a Massachusetts-based pharmaceutical company focused on providing non-opioid pain treatments for well-defined patient populations with significant unmet needs.
Tremeau’s unique approach to acute and chronic pain in select conditions is rooted in the mechanism of action, documented efficacy, and clinically differentiated profile of COX-2 selective NSAIDs.
Tremeau’s lead clinical stage product, TRM-201 (rofecoxib), is a COX-2 selective NSAID and a potent non-opioid analgesic with a well-established benefit-risk profile.
1 Chang D, et al. The Analgesic Efficacy of Etoricoxib Compared with Oxycodone/Acetaminophen in an Acute Postoperative Pain Model: A Randomized, Double-Blind Clinical Trial. Anesth Analg 2004;99:807–15
2 Malmstrom K, Kotey P, Coughlin H, Desjardins PJ. A randomized, double-blind, parallel-group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and acetaminophen with codeine using the dental impaction pain model. Clin J Pain. 2004;20(3):147-55.
3 Australian Prescribing Information. ARCOXIA. Updated May 8, 2020. http://www.e-lactancia.org/media/papers/Etoricoxib-DS-MSD2017.pdf
4 US Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders
5 Cannon CP, Curtis SP, FitzGerald GA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2006; 368: 1771–81.
6 Nissen SE, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med 2016; :2519-2529.
7 Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013; 382: 769–79.
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9 McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med 2011; 8: e1001098.