Background: Many genetic therapies, including antisense oligonucleotides, RNA-based therapies, and biologics for treatment of neurological disorders require repeated intrathecal (IT) dosing via lumbar puncture (LP). LP can be challenging for individuals with complex spinal anatomy and can require repeat anesthesia and radiation exposures. Complications such as post-LP headache may occur. Consequently, patients may benefit from an alternative delivery method.
Objective: Currently, there are no US Federal Drug Administration (FDA) approved IT catheter and subcutaneous port systems for therapeutic delivery. The ThecaFlex DRx™ System, part of Alcyone’s Falcon™ Intra-CSF Delivery Platform, is designed to address this unmet need. ThecaFlex DRx™ has undergone extensive pre-clinical testing including design verification, in vitro functional testing, biocompatibility and extractables, drug-device compatibility, ovine in vivo safety and functionality studies, and extensive human factors usability evaluations, and has received Breakthrough Device Designation and CE Mark Approval in Europe.
Results: The safety and performance of ThecaFlex DRx™ is currently under evaluation in a two-stage IDE clinical trial (PIERRE, NCT05866419) delivering nusinersen to individuals with spinal muscular atrophy (SMA). In stage 1, 10 participants were enrolled, implanted, infused with nusinersen and followed for 30 days. During stage 1, ThecaFlex DRx™ performed as intended, and no device-related infections or device-related adverse events were observed. After reviewing these data, FDA approved stage 2, which will enroll 80 patients across the U.S. and Europe. Concurrently, an IND study (PIERRE-PK, NCT06555419) will co-enroll 55 PIERRE participants to evaluate nusinersen pharmacokinetics (PK). Plasma PK samples obtained following LP and ThecaFlex DRx™ administration will be compared to determine if nusinersen concentrations are equivalent between delivery methods.
Conclusions: ThecaFlex DRx™ may improve the IT delivery experience through subcutaneous delivery of therapies to the CSF, potentially enabling cerebrospinal fluid (CSF) sampling and possibly reducing need for anesthesia and/or radiation. ThecaFlex DRx™ may be applicable to broad populations suffering from neurological disorders.