Unmet Clinical Need
Tramadol is a popular pain medication prescribed over 40 million times each year in the United States for moderate to severe acute, chronic and neuropathic pain. Its use has increased significantly because tramadol is believed to be a safer and less addictive alternative to schedule II opioids such as oxycodone and tapentadol . Tragically, millions of patients do not obtain pain relief from tramadol because they are unable to metabolize the drug to its active form. In some patient populations, 1 in 3 patients will not obtain adequate pain relief from tramadol either because they are also taking one of many common antidepressants that compete for the enzyme that metabolizes tramadol to its active form, or because they have a genetic variant in the same enzyme . The need to switch non-responders to schedule II opioids increases the risk of developing addiction and adds costs and inconvenience. Still other patients metabolize tramadol too quickly, causing common intolerance (nausea) and rarely, life-threatening side effects that include respiratory depression. The recommends against using tramadol in children and nursing mothers in the event either is a fast-metabolizer. There is therefore a critical need for a new tramadol-like pain medication that is effective without requiring metabolism, but that enjoys the same safety and lower addictive potential as tramadol.
Omnitram is Developed
To meet this critical need, Syntrix developed Omnitram, a proprietary solution to tramadol failure that provides the body with the primary active metabolite of tramadol, O-desmethyltramadol, in a precise timed delivery without requiring metabolic activation. Pain relief using Omnitram results from a dual mechanism involving mu-opioid receptor activation and inhibition of the reuptake of norepinephrine (see below).
When Syntrix initially began its program to create a new and improved tramadol-like pain medication, it unexpectedly discovered that it was impossible to simply administer the active metabolite of tramadol directly; doing so resulted in rapid clearance of the molecule and wide variation in blood levels. Overcoming this setback required Syntrix go back to the drawing board. For over a year company scientists tirelessly dedicated themselves to finding a way to correctly deliver the active metabolite to resistant patients. After countless formulations and thousands of samples tested, Omnitram was finally born.
The technology replicates the temporal delivery of ideal liver metabolism, employing slow-release technology to control the rates of hydration, dissolution and erosion in the stomach to deliver the active metabolite in a precise temporal blood profile that matches the profile of tramadol conversion to O-desmethyltramadol by liver metabolism. Because Omnitram properly delivers the appropriate blood levels of the active tramadol metabolite without requiring metabolism, it provides pain relief in patients who would otherwise fail to obtain pain relief from tramadol because of impaired metabolism, as well as preventing dangerously high blood levels of the active metabolite in patients whose genetic make-up causes them to metabolize tramadol excessively fast.
Successful Double-Blind Randomized Phase 1B Trial: Safe and Effective with Analgesia as Good as Tramadol
A successful 43-subject phase Ib study of Omnitram met its primary endpoint, providing analgesia equivalent to tramadol (P<.01) as shown in the Figure (right) while also providing evidence that it matched the tramadol pharmacokinetic profile, was safe, and was able to rescue metabolic defects in both a poor metabolizer and an ultra-metabolizer.
The Omnitram Market
The global market for Omnitram is over $2 billion. Omnitram targets the existing world opioid and tramadol markets with a “better” tramadol at a time when the continued use of Schedule II opioids is growing ever more controversial for prescribers. Retail U.S. sales of just the generic forms of hydrocodone, oxycodone, fentanyl and tramadol total over $6.1 billion. Tramadol itself is widely prescribed, with over 40 million prescriptions in the U.S. alone. Globally, tramadol sales are well over $2.0 billion. Omnitram is expected to be efficacious in acute and chronic moderate to server pain. Omnitram’s dual mechanism of pain relief is also expected to be effective in treating neuropathic pain, a type of pain that is particularly difficult to treat with current therapies. Opioids are frequently ineffective and other treatments such as gabapentin (Neurontin™) are associated with significant side effects. No current single drug treatment is effective in more than half of patients, and therefore novel therapeutic approaches are urgently needed. Approximately 26 million patients are affected worldwide and the global market for neuropathic pain is projected to reach $18 billion by 2020.