Introduction

We describe the effect of Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR) on women with recurrent or persistent stress urinary incontinence (SUI) after continence surgery.

Methods

Analysis includes data from women enrolled in Cook MyoSite-sponsored SUI studies who underwent prior continence surgery (e.g., urethral sling, bladder neck suspension) and presented with incontinence episode frequency (IEF) of ≥3 stress leaks over 3 days and ≥3 g 24-hour pad test. Twenty-one women who received 1 treatment of 10 (n=5), 50 (n=2), 100 (n=4), or 200 x 10⁶ (n=10) AMDC-USR were treated in open-label studies (NCT00847535, NCT01008943) and 17 women who were randomized 2:1 to receive 150 x 10⁶ AMDC-USR (n=11) or placebo (n=6) and 1:1 for 1 or 2 treatments were treated in a double-blind trial (RCT, NCT01382602). SUI was assessed by 3-day diaries at baseline and 1, 3, 6, and 12 months for all studies and at 2 years in the RCT. RCT patients were unblinded after 12-month visits.

Results

Median baseline stress IEF per 3 days was 12 leaks for open-label studies, and 11 leaks for AMDC-USR and 27.5 leaks for placebo in the RCT. In the RCT, the AMDC-USR group tended to be younger (51 yr vs. 64 yr), had a lower percentage with stage 1-2 pelvic organ prolapse (9% vs. 67%), and better 24-hour pad tests (45 g vs. 76 g) than placebo. In open-label studies, 18 women completed 12-month visits; 67% (12/18) had ≥50% IEF reduction, 44% (8/18) had ≥75% IEF reduction, and 39% (7/18) reported ≤1 leak over 3 days. Similarly, 12-month responder rates for the RCT AMDC-USR group were 73% (8/11) for ≥50% IEF reduction, 64% (7/11) for ≥75% IEF reduction, and 36% (4/11) for ≤1 leak per 3 days. During the RCT, a higher percentage of the AMDC-USR group met IEF reduction endpoints than placebo (Figure). Eight AMDC-USR RCT patients completed 2-year diaries; 100% (6/6) of women with ≥50% IEF reduction at 12 months also met the endpoint at 2 years. All (6/6) RCT placebo patients elected to receive open-label AMDC-USR after unblinding; at final follow-up, 3 patients had ≥50% IEF reduction compared to 12-month diaries. No AMDC-USR safety signals were identified._x000D_

Conclusions

AMDC-USR may be a novel, safe, durable therapy for the challenging patient population with recurrent or persistent SUI after continence surgery.

Funding

Cook MyoSite, Incorporated