Catalyst conducted its initial series of safety and efficacy evaluations in a number of animal and in-vitro laboratory tests. Key results include:
- In visual safety testing of treated rats exposed for 90 days to CPP-115, vigabatrin, and placebo, CPP-115 caused substantially less retinal damage than vigabatrin at well above the expected therapeutic doses.
- The oral pharmacokinetic behavior (PK) of CPP-115 in rats supports further development as an orally delivered pharmacotherapy.
- CPP-115 was found to not inhibit or induce metabolic enzymes and is not itself metabolized. As a result, drug-drug interactions or other metabolism-related side effects are unlikely. Additionally, non-metabolized drugs are advantageous for treating drug addicts; a population that often has impaired liver function.
- With the exception of its biochemical target, GABA-aminotransferase, CPP-115 did not show any clinically significant binding to 111 of the most prevalent receptors, proteins and transporters. Additionally, CPP-115 showed no binding to other GABA–related targets (GABA receptors and transporters). Therefore, CPP-115 is very specific and is not likely to induce drug-drug interactions or unintended side effects.
- CPP-115 did not show any interference with the hERG channel and is therefore not likely to induce heart arrhythmias.
- CPP-115 did not show any abnormalities in an in-vitro battery of genotoxicity tests and thus is not likely to be carcinogenic.
- CPP-115 did not show any inhibition of AST and ALT at doses far above the expected therapeutic dosage. This is in contrast to vigabatrin's known inhibition at therapeutic doses of these key liver transaminase enzymes.
- CPP-115, like vigabatrin, was found to significantly reduce seizures in accepted animal models of epilepsy, as evaluated by the National Institutes of Health's Anticonvulsant Screening Program (ASP), at lower doses than vigabatrin.
- CPP-115 was found to eliminate cocaine-related conditioned place preference and significantly reduced cocaine-induced dopamine surge, key tests needed to demonstrate a drug's effectiveness as a potential treatment for stimulant addiction. These effects were observed at doses more than 100 times lower than that needed by vigabatrin to achieve the same effect.
"These results demonstrate that CPP-115 has great promise as a pharmacotherapy for treating both stimulant addiction and epilepsy," said Dr. Steven Miller, Catalyst's Chief Scientific Officer. "This initial battery of tests addressed the most common safety concerns of new molecular entities, along with retinal toxicity. All of the results definitively demonstrated CPP-115's favorable safety profile, biochemical specificity, bioavailability, metabolic stability and potential efficacy. The pharmacological target of CPP-115 is the same as is associated with Sabril ® (vigabatrin), which is an approved, effective epilepsy drug. As a result, the development pathway going forward is well understood."
The Company will host a conference call today to discuss the CPP-115 study results.