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.