SBIR-STTR Award

Direct to Phase II

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.

Public Health Relevance Statement:
Project Narrative Benign Prostatic Hyperplasia (BPH) is a growing problem that severely impacts quality of life for up to 40 million patients in the US alone. Current established treatment options are limited to drugs which have limited efficacy, and surgery which has a high risk of sexual side effects. Delivered through a flexible cystoscope in an office setting without causing tissue damage, we expect that the Spring System will be superior to other minimally invasive therapies in 1) long-term effectiveness, 2) complication rate, 3) cost-effectiveness as enabled by low cost of goods, 4) ease of placement, and 5) patient comfort.

Project Terms:
Acute; Adoption; Adverse drug effect; Adverse effects; Adverse event; Aging; Anatomic Models; Anatomy; Animals; base; Benign Prostatic Hypertrophy; biomaterial compatibility; Cadaver; Canis familiaris; Chronic; Clinical; Clinical Research; Clinical Trials; Complication; Control Animal; cost; cost effectiveness; cost efficient; Cystoscopes; cytotoxicity; Data; design; Device Safety; Devices; Dry Orgasm; Effectiveness; Energy Therapy; Ensure; Erectile dysfunction; Excision; experience; flexibility; follow-up; Freedom; Frequencies; genotoxicity; Healthcare Systems; high risk; Histopathology; Human; Imagery; Implant; implant design; implantation; International; Investigation; irritation; Left; Libido; Life; Liquid substance; Magnetic Resonance; male; Mechanics; men; Methods; migration; minimal risk; minimally invasive; Modeling; Morphology; nitinol; Obstruction; Operative Surgical Procedures; Patients; Performance; Pharmaceutical Preparations; Phase; Postoperative Pain; pre-clinical; pre-clinical research; Preclinical Testing; Preparation; prevent; Procedures; Property; Prostate; prostate transurethral resection; prototype; Quality of life; reduce symptoms; Research Contracts; response; Risk; risk minimization; safety and feasibility; Sample Size; Services; Specimen; Stents; Sterilization; System; Testing; Tissues; tool; Toxic effect; Training; Urethra; Urethrostomy; urinary; Urinary Retention; Urine; Urologist; Validation; verification and validation