Auto-Injectable Diazepam Formulation for Rapid Treatment of Uncontrolled Seizures

The program outlined in this Fast Track application has been designed to accelerate the development and commercialization of the DiazePenfor the treatment of uncontrolled seizures in persons with epilepsyThe envisioned product would replace the current standard of carediazepam rectal gelDiaStatwith a novel formulation for rapid delivery via subcutaneous injectionFor this effortXeris will use its proprietary formulation platformXeriSolwhich has already demonstrated feasibility of a very low volumestable diazepam with pharmacokinetics similar to DiaStatSuccessful completion of the aims will advance development of the DiazePenthrough the formulation optimization and nonclinical phaseIND application and manufacture of clinical supplies for a future Phaseclinical trial that will be sponsored by Xeris PharmaceuticalsThis research is directly relevant to the NINDS which is explicitly interested in the development of innovative therapeutics for neurological disordersincluding therapeuticsdrugsbiologicsand or devicesfor treatment of neurological disordersand technologies methodologies to deliver therapeutics to the central nervous systemThis proposal envisions six main objectives to significantly advance development of an auto injectable diazepam as a first lineat home treatment for uncontrolled seizuresOptimize XeriSolnon aqueoussolublestable diazepam formulations to provide the desired pharmacokineticPKprofile and confirm container closure compatibilityManufacture at least threeGLP batches of non clinical supplies of the optimized formulations and place these supplies on a short term stability studyreal time and acceleratedConduct IND enabling animal studiesaAday safety tolerability study in rats evaluating threeXeriSol diazepam formulations by daily subcutaneous and intradermal routes of injectionbA comparative GLP PK study in mini pigs with Xerisnon aqueous diazepam and DiaStatThis study will seek to demonstrate pharmacological comparability between the two products administered via intradermal and subcutaneous injection with respect to tolerability various PK parameters including CmaxTmaxand AUC compared to DiaStatrectal gelManufacture twocGMP clinical batches of the drug product formulation in vials for the first clinical trial and place this batch on an ICH compliant long term stability studyConduct a comprehensive risk analysis and formative comparative human factors study with a DiazePenauto injector and the commercial rectal gel applicatorDiastatAcuDialPrepare and submit an amended IND application to the FDA seeking clearance for a Phaseclinical study