IEC 2023 | Recent findings from the X-TOLE study of XEN1101 in epilepsy

The compound XEN1101 is a novel, potent, potassium channel opener, and it’s in the development for the treatment of epilepsy and for other diseases. There has been a large Phase IIb study with quite positive and impressing results. Our poster was about a post-hoc analysis from the open label extension of this drug.

As you know, we aim at achieving seizure freedom in patients with epilepsy, or at least a marked reduction in seizure frequency if seizure freedom cannot be achieved and in a balance with a high tolerability of a drug. So, the most important goal of all is to improve the quality of life of persons with epilepsy. And regularly this is being measured in clinical trials and also in clinical practice by the QOLIE-31, the quality-of-life instrument in epilepsy with 31 items. As it is usual after the completion of a double-blind trial, it’s possible for the study participants to continue in an open label extension study. And of the 285 patients who completed the double-blind phase of the study, more than 96%, i.e., 275 patients, entered the open label extension. The open label extension runs now for a couple of years, but we present data on the first year of the open label extension.

So, the QOLIE-31 has been administered at baseline visit for the double-blind phase, at the end of double-blind phase, and then in three months intervals for the first year of the open label extension. For the analysis, we looked at the overall population and especially at the seizure free group. I can tell you that both groups had the lowest mean QOLIE-31 scores at baseline for the seizure worry subscale, and the highest score was for emotional well-being. So, on follow up, there were improvements in the mean QOLIE-31 total score and most subscales at the end of the double-blind phase and during the first 12 months of open label extension, compared to baseline. There was a difference between the overall group and the seizure-free group. There are defined thresholds for clinically important improvements, for the minimal important changes. There were, in both groups, important changes in seizure worry, social functioning, and medication effects. And there were even higher and better improvements for the seizure free group.

Before I get to the limitations, I will talk about the meaning of the findings. It means many aspects of the QOLIE-31 have been improved from baseline of the double-blind phase throughout the open label extension first year. The study has a limitation and that is we did not delineate between those patients who were on the study drug from the beginning of the double-blind phase and those who were on placebo. So that is something that we will have to do for further studies with the compound. I think it’s a finding you can see with many other aspects in drug trials that seizure free patients have a higher benefit in diverse domains of daily living. So, we differentiated that, but there are certainly other things we could look at, like what about different degrees of response? What about the 50% responders? 90% responders? As compared to the non-responders… or maybe even going into medication and so on, so there’s a good field of research required.