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Xenon Presents Positive XEN1101 TMS Pharmacodynamic Phase 1 Data at 14th Eilat Conference(May 15, 2018)
Company to Hold Conference Call at 8:00 am ET Today
XEN1101 Pilot TMS-EEG Data Demonstrates Statistically Significant Effect of 20mg Dose versus Baseline (p<0.01) and Greater Effect on TMS-EMG Resting Motor Threshold at Significantly Lower Dose When Compared to Ezogabine
Phase 1 Pharmacokinetic Data Supports Potential for Once Daily Dosing
BURNABY, British Columbia, May 15, 2018 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a clinical stage biopharmaceutical company, today presented positive interim data from its ongoing XEN1101 Phase 1 clinical trial in a podium presentation at the 14th Eilat Conference on New Antiepileptic Drugs and Devices (Eilat) held in Madrid, Spain.
XEN1101 is a Kv7 potassium channel opener being developed by Xenon for the treatment of epilepsy including: treatment-resistant adult and pediatric focal seizures as well as rare, pediatric forms of epilepsy, such as EIEE7, an early infantile epileptic encephalopathy associated with mutations in the KCNQ2 gene encoding the Kv7.2 potassium channel; and potentially other neurological disorders.
Today, Xenon presented interim data from its ongoing XEN1101 Phase 1 clinical trial, which is evaluating the safety, tolerability and pharmacokinetics of both single ascending doses (SAD) and multiple ascending doses (MAD) of XEN1101 in healthy subjects, along with results from the completed Phase 1a pilot transcranial magnetic stimulation (TMS) study in 8 healthy subjects. The pilot TMS study was designed to assess XEN1101’s ability to inhibit cortical excitability, an important CNS effect observed with anti-epileptic drugs (AEDs). Based on this pilot Phase 1a TMS study, Xenon has initiated a double-blind, placebo-controlled, randomized cross-over Phase 1b TMS study, which is expected to include approximately 15 to 20 healthy subjects and be completed by mid-year, with data expected in the second half of 2018.
Dr. Simon Pimstone, Xenon’s Chief Executive Officer, said, “The interim XEN1101 Phase 1 clinical data presented today are very exciting. We believe that the pre-clinical and interim clinical data presented, demonstrate a number of significant benefits of XEN1101 when compared to historical data for ezogabine, an earlier generation potassium channel modulator. These benefits include both pharmacokinetic (PK) and apparent safety benefits as well as achievement of a key pharmacodynamic (PD) readout at a 20 mg dose, which approximately 1/20th of that reported in historical data for ezogabine. The XEN1101 PK profile from the current Phase 1 clinical trial, supports the potential for once daily dosing with XEN1101 versus ezogabine’s three-times daily dosing. From a safety perspective, the majority of adverse events were mild and resolved spontaneously, with an overall profile showing XEN1101 as safe and well tolerated. Importantly, this safety has been observed at drug exposures where we have now shown XEN1101 having an inhibitory effect on cortical excitation in humans.”
Dr. Pimstone added, “In order to obtain an early PD read-out, we used the TMS assay as a measure of cortical excitability and indicator of drug activity in the target CNS tissue. We are pleased to see a robust PD effect in the TMS assay in healthy human volunteers. When compared with the historical data generated with ezogabine, XEN1101 had approximately twice the effect at significantly lower doses.”
Dr. Isabella Premoli, postdoctoral research worker at King’s College London and investigator for the XEN1101 Phase 1a TMS pilot study and Phase 1b placebo-controlled cross-over study, stated, “The TMS-EMG and TMS-EEG assays have been used for a number of years to measure cortical excitability and study the effect of approved AEDs, such as ezogabine, levetiracetam, and lamotrigine, when tested in healthy subjects. Based on our experience with TMS, we are extremely encouraged by the data generated in the XEN1101 Phase 1a TMS pilot study, which demonstrate an effect of XEN1101 on cortical hyperexcitability in healthy volunteers. In the TMS-EMG component, XEN1101 is clearly impacting the resting motor threshold: at the 20 mg dose, we see an effect that appears significantly greater than that observed with ezogabine, at a significantly lower dose, when compared to the historical data. In the TMS-EEG component, all three subjects at the 20 mg dose had a statistically significant effect when compared to their individual baseline measurements with changes observed in what appears to be a distinct pattern for all three subjects, suggesting TMS-EEG can detect an effect related to the Kv7 channel mechanism. Overall, we believe XEN1101 is having a robust and meaningful effect on cortical hyperexcitability at the single-subject level.”
Dr. Premoli continued, “Our work with Xenon underscores our belief that the TMS assay has the potential to be used more broadly during the early stages of AED development to potentially provide early read-outs of a pharmacodynamic effect. I am looking forward to further validating these positive results from the XEN1101 Phase 1a TMS pilot study with the data generated from the XEN1101 Phase 1b TMS placebo-controlled cross-over study, which we expect to complete later this quarter.”
Summary of XEN1101 Interim Phase 1 Clinical Data / Phase 1a Pilot TMS Study
- The XEN1101 interim Phase 1 results include data from five SAD cohorts (n=28, placebo=6) ranging in dose from 5 to 30 mg, and one MAD cohort at a 15 mg dose (n=6, placebo=2).
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