Spring System for Permanent Relief of Urinary Obstruction related to Benign Prostatic Hyperplasia

Period of Performance: 09/15/2017 - 07/31/2018

$637K

Phase 2 SBIR

Recipient Firm

Zenflow, Inc.
SOUTH SAN FRANCISCO, CA 94080
Principal Investigator

Abstract

Project Summary/Abstract Significance: Urinary retention, frequency, and urgency related to benign prostatic hyperplasia (BPH) represent an unmet clinical need for many millions of men in the US. Medications can be expensive, have side effects like loss of libido, and prove ineffective in 30-43% of patients. Surgery is effective, but can result in post-operative pain and carries a high risk of permanent sexual side effects such as retrograde ejaculation and erectile dysfunction. A number of shortcomings have prevented minimally invasive attempts from attaining widespread adoption. Mechanical devices have failed due to difficult placement, migration, and encrustation caused by urine exposure, whereas energy therapies have failed to achieve durable results. Zenflow has developed the Spring System to provide a superior minimally invasive and permanent solution for men who experience inadequate relief or side effects from drugs, but decline to undergo invasive surgical procedures such as transurethral resection of the prostate (TURP). Unlike other minimally invasive attempts, the Spring nitinol implant is delivered through a flexible cystoscope in an easy, ten-minute office procedure that does not damage tissue. With uniquely low COGS of less than $200, the Spring will also substantially reduce costs to the healthcare system substantially over all existing treatment options. Preliminary Data: We have performed preclinical validation in two acute canines, thirteen chronic canines (nine followed to at least 90 days), and ten cadaver specimens. After refining the placement procedure in early studies, we have verified that the Spring implant can be placed accurately and reliably by a trained urologist. In animal studies, the implant has demonstrated its ability to fully invaginate into the urethral wall, expand the urethral lumen, and avoid urine exposure. No encrustation has occurred, and no migration has occurred when the device was placed property. Delivery of the implant across all animal studies took three minutes on average. We have supplemented these studies with a comprehensive suite of bench-top verification and validation tests, which confirm deliverability and circumferential strength of the implant, and biocompatibility and mechanical integrity of the implant and delivery system. Specific Aims: This project entails preclinical testing of the Spring implant and delivery system for eventual application to human patients suffering from BPH-related obstruction. In Specific Aim 1, we will perform preliminary bench-top V&V testing in preparation for human clinical trials. The suite of tests will resemble those outlined in the De Novo 510(k) summary for the NeoTract UroLift device, which will be used as a predicate device for 510(k) submission. These tests will verify 1) biocompatibility of the implant and delivery system fluid path including cytotoxicity, sensitization, irritation, acute and chronic toxicity, genotoxicity, subchronic toxicity, and implantation, 2) package integrity, aging, transit testing, and shelf life, 3) sterilization validation, 4) magnetic resonance compatibility, and 5) benchtop performance and simulated use. In Specific Aim 2, we will assess long term safety and feasibility of the Spring System in a six-month chronic GLP animal study involving eight male hound dogs. Six treatment animals will receive a Spring implant and two control animals will undergo a simulated procedure. We will log all relevant adverse events detailed in the FDA guidance document for BPH devices and will perform histopathology on all dogs after sacrifice to assess long-term tissue response. In Specific Aim 3, we will develop a tool and method for safe and easy removal in an office setting. To validate the ease and effectiveness of this tool, we will perform an additional chronic canine study in two dogs where the Spring device will be implanted, left in place for six months, then removed. After these aims are achieved, we will submit an Investigational Device Exemption (IDE) application to the FDA and initiate a US human clinical trial.