10_Omnitram_Grant

Syntrix Receives $1.8M Grant to Develop Omnitram for Acute and Chronic Pain

Congratulations to Syntrix scientists on their new grant for $1.8M from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH). The project title is “Overcoming Tramadol Resistance In CYP2D6 Poor Metabolizers.” Here is the public health relevance from the proposal: “Tramadol is a widely prescribed analgesic, but 10% of the U.S. population is resistant to Tramadol analgesic effects. This project aims to overcome Tramadol resistance for pain medication by developing a new therapeutic, and corresponding Phase I clinical trial.”

Abstract from the proposal: Tramadol is a widely prescribed analgesic, with over 25 million prescriptions and 565 million in retail sales in 2009, making it among the bestselling generic drugs. One of the advantages of tramadol over traditional opioids is its lower risk of opioid dependence, resulting in it having an unscheduled status in the U.S. and other countries. Although its mode of action is not completely understood, its analgesic activity is due to synergy between both the parent drug and the desmethyltramadol (M1) metabolite. The production of M1 and its opioid activity is critically dependent on the polymorphic isoenzyme of the debrisoquinetype, cytochrome P450 2D6 (CYP2D6). Approximately 10% of Caucasians have a genotype that results in reduced activity of CYP2D6. These individuals are poor metabolizers (PM) of tramadol, and their M1 serum concentration is significantly less than normal subjects. Several well controlled clinical trials have shown that the analgesic effect of tramadol is decreased or absent in PM subjects who have low CYP2D6 enzymatic activity. The impact of tramadol resistance in 10% of the U.S. population with low or absent CYP2D6 activity is significant, with upwards of a million patients receiving inadequate analgesia from tramadol therapy annually. Further, the need to switch nonresponders to traditional opioids increases their risk of opioid dependence. Within this need-analysis, there exists an opportunity to develop an improved tramadol that would be effective in all patients. Such a product would be expected to be quickly adopted by the market and displace existing tramadol sales. Based on extensive single-dose/steady-state human pilot data gathered in the SBIR Phase I segment, we identified a new proprietary M1/Tramadol tablet (SR105) that we hypothesize will overcome tramadol resistance in PMs by directly supplementing these patients with the M1 metabolite that they are incapable of generating on their own. By providing both the M1 metabolite and the parent drug, the entire spectrum of opioid and monoaminergic activity will be restored in subjects with the PM phenotype. This SBIR Phase II proposal aims to develop and finalize the required elements to open an IND with the FDA and to conduct a phase 1, two-segment, randomized cross-over clinical trial in 60 subjects that will begin to test our hypothesis.

Read about Omnitram in our pipeline.