Opioid drugs can be life threatening. It is not uncommon to hear stories about folks being prescribed opioids for injuries, that eventually leads to their dependence on the drug(s). One such story from the Center for Disease Control and Prevention website talks about a man who lost his life at the age of 22 years due to opioid overdose. He was prescribed opioid drugs for a minor accident but his eventual addiction to the drugs led to his premature death.
Opioids such as morphine, fentanyl, tramadol - have been the primary sources of treatment for non-cancerous chronic and terminal pain. However, our bodies tend to build up tolerance for these drugs, resulting in dependence and finally, addiction. According to the World Health Organization (WHO), in 2021 20% of the global population using drugs took opioids. WHO records show that in 2019 about 480,000 deaths resulted from opioids out of which about 120,000 were from overdose.
The other type of drugs very commonly used for pain are the non-steroidal anti-inflammatory drugs (NSAID) such as ibuprofen, naproxen, etc. The respiratory, cardiovascular, gastrointestinal, and renal systems are affected by the NSAIDs — gastrointestinal bleeding being a common symptom of NSAID usage. The side effects of using these drugs are more prominent in individuals aged over 65 years.
Vertex Pharmaceuticals has come up with a non-opioid, small-molecule, analgesic, oral drug VX-548, which is highly selective for the voltage-gated sodium channel Nav1.8 expressed in the peripheral nervous system.
In a recent press release on the Phase 3 trial (the stage of clinical trial where a drug’s effectiveness and safety are tried against established standard treatments) of this drug, the company announced promising results for treating acute surgical pain resulting from abdominoplasty (a surgical procedure used to make the abdomen firmer and thinner, and mostly associated with soft tissue pain) or bunionectomy (a surgical procedure for correcting the positioning of toes, and mostly associated with bone pain). Both the trials were double-blinded, placebo-controlled, randomized and included more than 1000 patients — 1118 for abdominoplasty and 1073 for bunionectomy. These patients aged 18 to 80 years, with moderate to severe post-surgical pain were administered orally with VX-548 or a combination of hydrocodone bitartrate (opioid drug)/acetaminophen or placebo. For both conditions, VX-548 was significantly more effective and faster in treating the post-surgical pain than the placebo. However, effectiveness of VX-548 was similar to that of the opioid drug/acetaminophen combination.
Another group of 256 patients were tested for evaluating the drug’s safety. While no severe adverse effects (SAEs) were reported for the drug, most adverse effects (AEs) were found to be in the mild to moderate range.
Vertex Pharmaceuticals plans to file for the approval of VX-548 to the Food and Drug Administration (FDA) by the middle of 2024.
The voltage-gated sodium channel Nav1.8 present in the peripheral nervous system, is responsible for pain signaling to the brain. VX-548 can selectively inhibit Nav1.8, thus blocking those pain signals temporarily at their source.
The approval of such a drug that comes without the detrimental side-effects of opioids, could be momentous in the search for non-addictive pain medication.
References:
https://www.who.int/news-room/fact-sheets/detail/opioid-overdose
Jones, J.; Correll, D. J.; Lechner, S. M.; Jazic, I.; Miao, X.; Shaw, D.; Simard, C.; Osteen, J. D.; Hare, B.; Beaton, A.; Bertoch, T.; Buvanendran, A.; Habib, A. S.; Pizzi, L. J.; Pollak, R. A.; Weiner, S. G.; Bozic, C.; Negulescu, P.; White, P. F. Selective Inhibition of NaV1.8 with VX-548 for Acute Pain. New England Journal of Medicine 2023, 389 (5), 393–405. https://doi.org/10.1056/NEJMoa2209870.
Benyamin, R. Opioid Complications and Side Effects. Pain Phys 2008, 2s;11 (3;2s), S105–S120. https://doi.org/10.36076/ppj.2008/11/S105.
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Gupta, S.; Atcheson, R. Opioid and Chronic Non-Cancer Pain. J Anaesthesiol Clin Pharmacol 2013, 29 (1), 6–12. https://doi.org/10.4103/0970-9185.10578 Assessed and Endorsed by the MedReport Medical Review Board