An Implantable Micropump for Enhanced Metronomic Chemotherapy for Leptomeningeal Brain Cancer

Project Summary The current treatment of leptomeningeal brain cancers, occurring in the space surrounding the brain which is bathed by cerebrospinal fluid (CSF), is highly ineffective. The blood-brain barrier (BBB) limits the diffusion of systemically-delivered drugs into the CSF. For those drugs that do cross the BBB, rapid CSF turnover reduces drug concentration in a matter of hours. The standard of care treatment (twice-weekly lumbar puncture) results in CSF drug concentrations at initially high toxic levels, which then drop through the therapeutic window, and then become sub-therapeutic. There is a great unmet need for a drug-delivery device that maintains chemotherapeutic drug concentrations within the therapeutic window over an extended period, thus significantly improving outcomes and reducing toxic side effects. Fluid Synchrony has developed a 200 µL pump mechanism which enables chronic localized metronomic dosing (frequent small infusions every 3 hours) to maintain drug concentration in the therapeutic window, thereby improving tolerability, safety and effectiveness of treatment. The FDA has granted a humanitarian use device (HUD) designation exclusively to our micropump for intraventricular chemotherapy of leptomeningeal cancers. We will initially target pediatric brain cancer populations, as pediatric populations are overlooked by the medical device industry and current practice is to adapt adult devices which results in unnecessary risk and high costs. There is an urgent unmet need for devices specifically designed for pediatric patients. The FDA has made it a priority to expedite pediatric medical device review, as evidenced by the Pediatric Research Equity Act and the Pediatric Medical Device Safety and Improvement Act. The opportunity to dramatically improve outcomes in pediatric high-risk populations is compelling. This SBIR will leverage capabilities from our demonstrated 200 µL pump to develop a fully integrated 3 mL implantable pump, incorporating established clinical needs. In Phase I we will complete development of an automated, metronomic pump mechanism capable of safe, repeated microinfusions to sustain a safe, therapeutically effective drug concentration, and will perform critical bench tests to demonstrate that pump performance meets user requirements and that the chemodrug topotecan and the pump are mutually compatible. In Phase II we will complete all bench tests and pre-clinical studies necessary to support approval of a feasibility clinical study, and will submit data for IRB/IDE approval of such feasibility clinical study. We will additionally implement full QSR / cGMP, appropriate to support an HDE market application. At the conclusion of this SBIR we will have IRB/IDE approval and be positioned to initiate a clinical study.