The current treatment of leptomeningeal brain cancers, occurring in the space surrounding the brain which isbathed by cerebrospinal fluid (CSF), is highly ineffective. The blood-brain barrier (BBB) limits the diffusion ofsystemically-delivered drugs into the CSF. For those drugs that do cross the BBB, rapid CSF turnover reducesdrug concentration in a matter of hours. The standard of care treatment (twice-weekly lumbar puncture) resultsin CSF drug concentrations at initially high toxic levels, which then drop through the therapeutic window, andthen become sub-therapeutic. There is a great unmet need for a drug-delivery device that maintainschemotherapeutic drug concentrations within the therapeutic window over an extended period, thus significantlyimproving 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, therebyimproving 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 medicaldevice 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 apriority to expedite pediatric medical device review, as evidenced by the Pediatric Research Equity Act and thePediatric Medical Device Safety and Improvement Act. The opportunity to dramatically improve outcomes inpediatric high-risk populations is compelling. This SBIR will leverage capabilities from our demonstrated 200 µLpump to develop a fully integrated 3 mL implantable pump, incorporating established clinical needs. In Phase Iwe will complete development of an automated, metronomic pump mechanism capable of safe, repeatedmicroinfusions to sustain a safe, therapeutically effective drug concentration, and will perform critical bench teststo demonstrate that pump performance meets user requirements and that the chemodrug topotecan and thepump are mutually compatible. In Phase II we will complete all bench tests and pre-clinical studies necessary tosupport approval of a feasibility clinical study, and will submit data for IRB/IDE approval of such feasibility clinicalstudy. We will additionally implement full QSR / cGMP, appropriate to support an HDE market application. At theconclusion of this SBIR we will have IRB/IDE approval and be positioned to initiate a clinical study.
Public Health Relevance Statement: Narrative
The current treatment of brain cancers which occur in the space surrounding the brain that is bathed by
cerebrospinal fluid (CSF) is ineffective, because the CSF rapidly washes away any delivered chemotherapy
drug. The standard of care treatment results in chemotherapy drug concentrations that are at high, toxic levels
immediately after administration, then drop through the range where they are effective, then become low and
ineffective. Fluid Synchrony has demonstrated an implantable drug pump which maintains chemotherapy drug
concentrations so they are both safe and effective in fighting brain cancer, and in this effort we will complete the
development and testing required to move this impactful therapy into clinical testing.
Project Terms: <21+ years old>
