EAN 2022 | Design of the EPSILON trial of opicapone as an add-on to levodopa in early PD

It’s interesting to discuss that trial because the trial compares opicapone with a placebo for the treatment of patients with Parkinson’s disease without motor fluctuations. So, the main goal behind that trial and that design is to document if opicapone works in terms of improving the motor impairment associated with patients with Parkinson’s disease when compared with a placebo.

The context is that we are using COMT inhibitors, in this case of opicapone, just in patients with motor fluctuations. Now we are targeting a different population, patients that don’t have motor fluctuations, and what’s the rationale to conduct that trial. It’s interesting that, when we prescribe levodopa, we are always prescribing levodopa with carbidopa or benserazide. Those two compounds are enzyme inhibitors of the DOPA decarboxylase. So it’s another way to increase the exposure of patients to levodopa in the periphery, meaning more levadopa is available to cross to the brain.

So in some way, when we add a COMT inhibitor to a treatment with levodopa, this is not the first inhibition. We have already another inhibition for the same purpose. The interesting point is when we use carbidopa and benserazide, we use even in patients that don’t have motor fluctuations. So we are doing something for which now we are just conducting trials like the EPSILON to document if there is an effect. It seems a paradox, but that’s the way it is. Of course, it’s not the same pathway. It’s a different pathway, but the goal it’s the same, it’s to increase the availability of levodopa the brain. In that trial specifically, what we will try to document, if clearly there is data in terms of efficacy and safety that justify starting using opicapone early, and early in this case means starting opicapone even in patients without motor fluctuations.

It’s interesting that, in this trial, the main outcome it’s clearly the improvement in terms of motor disability, motor impairment. We will use the MDS-UPDRS Part III as the primary outcome. But, of course, the immediate following thought is to know if that strategy to use a COMT inhibitor early, even in patients that don’t have motor fluctuations will delay, I would say hard outcomes to occur. And those hard outcomes are onset of dyskinesia, onset of motor fluctuation, and even more onset of disabling motor fluctuation. So, yes, it’s not the main goal at this trial, but clearly this is the first step to try to evaluate that other objective.