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news.Synosia Therapeutics, a company that develops and intends to commercialise products for unmet medical needs in neurology and psychiatry, has presented data from a Phase 2a clinical study of adenosine 2a (A2a) receptor antagonist (SYN-115) in Parkinson’s disease.
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The data demonstrates that SYN-115 improves measures of motor and non-motor function in patients either alone or in combination with levodopa. The results clearly illustrate the value of perfusion magnetic resonance imaging (MRI) as a tool to rapidly evaluate the pharmacodynamic effects of new drugs in the brain.
SYN-115 is a potent and selective inhibitor of the A2a receptor. Synosia is developing the compound for the treatment of Parkinson’s disease and obtained rights to SYN-115 from Roche in 2007 for development in selected indications of the central nervous system.
Synosia Therapeutics said that the Phase 2a trial was a randomised, double-blind, placebo-controlled, cross-over study in patients with mild-to-moderate Parkinson’s disease. Patients were randomised to one week each of SYN-115, washout, and then matching placebo, or the reverse.
The effects of 60mg BID (N= 14) and 20mg BID (N=13) of SYN-115 in the absence of levodopa and in the presence of a low dose of levodopa were evaluated using a number of techniques, including functional magnetic resonance imaging (fMRI), clinical ratings such as the Unified Parkinson’s Disease Rating Scale (UPDRS), tapping speed, and cognitive tests.
The data presented demonstrate that, after correction for whole-brain CBF effects and for multiple comparisons, SYN-115 produced dose-responsive decreases in cerebral blood flow in regions of the brain known to be relevant to Parkinson’s. These decreases are entirely consistent with the expected mechanism of action of SYN-115.
In the 60mg cohort, tapping speed was improved (faster) by SYN-115 as compared to placebo, both before and during a sub-therapeutic IV infusion of levodopa.
Total UPDRS motor score was 20% lower (improved) with SYN-115 as compared to placebo when administered with levodopa. Considering UPDRS items individually, 10 of 13 items were better on SYN-115 than on placebo; improvement in two UPDRS measures of bradykinesia (finger taps and rapidly alternating movements of the hands) achieved statistical significance.
Additionally, the performance on the go/no-go task, a cognitive test considered to depend on dopaminergic function, was also improved by SYN-115 as compared to placebo. SYN-115 was well tolerated at both the 60 and 20 mg BID doses.
Kevin Black, principal investigator for the Phase 2a study, said: “These data provide clear evidence that SYN-115 penetrates the brain and produces changes in the activity of regions known to be sensitive to drugs used to treat Parkinson’s. These changes accompany improvements in selected measures of motor and non-motor functions in these patients.
“Additionally, through the successful utilisation of perfusion MRI to assess the impact of SYN-115 in specific regions of the brain, this study clearly demonstrates the utility of this technique to provide rapid, useful and clinically relevant information for the evaluation of new drugs for the treatment of CNS disorders.”
Ian Massey, president and CEO of Synosia Therapeutics, said: “The results for this study give us confidence that SYN-115 is having the anticipated and desired effects in the brain and has high potential to become an innovative medicine for the treatment of the motor and non-motor symptoms of Parkinson’s disease. Based on these important and exciting findings, we plan to initiate additional clinical studies to further evaluate the efficacy and safety of SYN-115.”