AUTOLOGOUS MUSCLE DERIVED CELLS FORURINARY SPHINCTER REPAIR IN WOMEN WITH STRESS URINARY INCONTINENCE:PRELIMINARY ASSESSMENT OF SINGLE AND MULTIPLE TREATMENT MODALITIES
L. CARR 1, L. TU 2,M. ROBERT3, D. QUINLAN 4, K. CARLSON 5,S. HERSCHORN 1, R. JANKOWSKI 6, R. DMOCHOWSKI7, M. CHANCELLOR 8;
1SunnybrookHlth.Sci. Ctr., Toronto, Canada, 2Ctr. Hosp.ier Univ.irede Sherbrooke, Sherbrooke, Canada, 3ob/gyn, Univ. ofCalgary, Calgary, Canada, 4Univ. of British Columbia,Victoria, Canada, 5Univ. of Calgary, Calgary, Canada,6Cook MyoSite Inc., Pittsburgh, PA, 7Vanderbilt,Nashville, TN, 8Oakland Univ. William Beaumont Sch. ofMedi, Royal Oak, PA.
Introduction: Augmentingsphincter function may be beneficial to patients with stress urinaryincontinence (SUI). Therefore, autologous muscle cell therapy, whichinvolves isolation and ex vivo expansion of cells fromskeletal muscle biopsies and subsequent injection into the urethralsphincter, is being investigated as a potential durable treatment.The effect of single and multiple treatment modalities is alsoexplored.
Objective: To assess the safety and efficacy of 1and 2 treatments (1Tx, 2Tx) of Autologous Muscle Derived Cells forUrinary Sphincter Repair (AMDC-USR) in women with SUI.
Methods:Women with predominant SUI who experienced an average of ≥1 stressincontinence episode/day were enrolled. After biopsy, patients wererandomized 2:1 to receive 150 x 106 AMDC-USR or vehicleplacebo and 1:1 to receive 1Tx or 2Tx. Intrasphincteric injectionswere administered at 9 circumferential locations, with secondtreatments administered 6 months after first treatments. Three-daydiaries of stress incontinence episode frequency (IEF), 24-hour padtests, and in-office pad tests were collected. The primary compositeefficacy endpoint was the percentage of patients with ≥50% IEFreduction or ≥50% reduction in either pad test 12 monthspost-treatment. Patients were unblinded after completing 12-monthvisits, and placebo patients could opt to receive open-labelAMDC-USR. Patients were followed for 2 years after initial treatment.Results are presented based on treatment received.
Results:Overall, 150 patients were biopsied and randomized, 143 patients weretreated (53 1Tx AMDC-USR, 40 2Tx AMDC-USR, 27 1Tx placebo, 23 2Txplacebo), 141 patients completed 12-month visits (51 1Tx AMDC-USR, 402Tx AMDC-USR, 27 1Tx placebo, 23 2Tx placebo), 49 placebo patientsreceived open-label AMDC-USR, and 126 patients completed 2-yearvisits (80 original AMDC-USR, 46 open-label AMDC-USR). Baselinecharacteristics were similar across groups. No AMDC-USR safetyconcerns were identified. With the composite endpoint, responderrates for both 1Tx and 2Tx AMDC-USR and placebo exceeded 80%;therefore, the study was halted at 61% (150/246) of its planned size.Post hoc analyses examined ≥50% IEF reduction, an accepted minimalclinically meaningful outcome in SUI studies, and more stringentendpoints of ≥75% IEF reduction and ≤1 stress leak/3 days. At 12months, ≥50% IEF reduction responder rates for 1Tx and 2Tx AMDC-USRdiffered by 10%, while responder rates for more stringent endpointswere more similar (Table 1). At 2 years, both 1Tx and 2Tx AMDC-USRhad similar responder rates for all IEF reduction endpoints.
Table1. Responder rates for IEF reduction endpoints at 12 months and 2years
Responses to AMDC-USR were durable withhigh percentages of patients maintaining responder status at 2 years(Table 2). Overall, 84% (37/44) of AMDC-USR patients with ≥50% IEFreduction at 12 months and available 2-year diaries also met thisendpoint at 2 years.
Table2. Percentage of patients who maintained response from 12 monthsto 2 years
IEFreduction endpoint maintained at 2 years
Overall, responder rates for ≥50% IEFreduction, ≥75% IEF reduction, and ≤1 stress leak/3 days weregreater for AMDC-USR than placebo, suggesting a potential treatmenteffect (Figure 1, left column). However, 1Tx and 2Tx placebo responserates differed for ≥50% IEF reduction (Figure 1, top row),complicating the interpretation of 1Tx and 2Tx efficacy.
Conclusions: Both 1Tx and2Tx AMDC-USR are safe and may provide durable reduction in IEF.Future studies are designed to further evaluate efficacy anddurability of single and multiple AMDC-USR treatments.