It’s true that XEN1101 at 6 hours outperformed ezogabine’s 400mg dose - but not at the same time period! Here are numeric values from the company’s press releases: No dimerazation or urinary retention was noted in the Phase 1 work although it was tested on a relatively limited sample of patients for a short time. The structure of the drug in theory prevents dimerization (which was the biggest complaint about ezogabine) and its selectivity and greater preference for the CNS over the kidney compared to ezogabine should stop the urinary retention AEs as well. In regards to safety, the drug is designed rationally to prevent the problems Ezogabine faced and should translate to better adverse event profile.
Main Takeaways: XEN1101 is a once-daily medication designed to be a well-tolerated Kv7 modulator with no titration, pigmentation, or other tolerability issues.Ī crude dose estimation for XEN1101 would take Ezogabine’s 1200mg maximum daily dosage and divide by 16 (XEN1101 is 16x more potent in animal models) and then divide by 3 (XEN1101 has a half-life that is three times longer) and would arrive at…25mg! Which just so happens to be the maximum daily dosage at which XEN1101 is being tested!īut that is too simplistic to put our money behind, right? We need to dive deeper in how XEN1101 compares to Ezogabine in human Phase 1 studies to make sure we have the necessary target engagement and long-term trough levels for efficacy. XEN1101 is designed to avoid “dimerazation” (contains tertiary aniline) Low dropouts and high OLE participation (95%) suggest ≤ 25mg well tolerated Half-life: “Longer than 24 hours” (can’t find exact number!)ĮC50, MES mouse model: 0.22μM (XEN1101 is roughly 16x more potent) XEN1101 Pharmacokinetic Data and Propertiesĭoses Selected, Phase 2b: 10mg, 20mg, or 25mg daily More PK variability leading to a wider range of plasma levels in patients
Not well tolerated, some patients can not tolerate maximum dosageĮzogabine vulnerable to “dimerazation” (at secondary aniline) -> pigmentation Half-life: 6 to 8 hours (cited as 7.5 hours on DrugBank) I know, confusing.Įzogabine Pharmacokinetic Data and Propertiesĭoses Approved: 200mg, 300mg, or 400mg three times daily Note for above: Retigabine and Ezogabine are the same drug, the names can be used interchangably.
0 kommentar(er)
