Autologous muscle derived cells for urinary sphincter repair (AMDC-USR) to treat stress urinary incontinence (SUI) was safe and durable, particularly for women who have undergone prior SUI surgery, a researcher reported.

In a randomized phase III study, 36.9% of women receiving AMCD-USR achieved a strong response (≥75% reduction in stress incontinence episode frequency at 12 months) versus 30.9% of women receiving placebo, according to Melissa R. Kaufman, MD, PhD, of Vanderbilt Medical Center in Nashville.

And among a subset of women who underwent prior SUI surgery, more than twice as many women receiving AMCD-USR achieved a ≥75% stress incontinence episode frequency (SIEF) reduction versus women on placebo, she said in a presentation at the American Urological Association virtual meeting.

Treatment of this subset of women is “the greatest unmet need,” said Michael B. Chancellor, MD, of Oakland University Beaumont School of Medicine in Rochester, Michigan, who presented a separate analysis that focused on the women in the study who underwent prior SUI surgery “A single injection of AMDC-USR may provide a safe and effective treatment option in this challenging population.”

“This is a unique technology that is a biologic for stress incontinence treatment,” Kaufman explained. “It is targeted for delivery to the external sphincter and [involves] minimally invasive in-office procedures for both biopsy and injection. The mechanism of action is hypothesized to be engraftment into the muscle at the injection site, forming new striated muscle and improving function, with exceptional potential then for durability.”

The multicenter IND2 study had 297 adult women, with an average of 14.4 stress leaks over 3 days, who were randomized 2:1 to either receive AMDC-USR or placebo, and who were further stratified by baseline severity and prior SUI surgery.

The primary endpoint of the study was actually ≥50% SIEF reduction at 12 months, however, “this was not discriminatory between placebo due to exceptional variability in the placebo effect,” Kaufman explained.

Thus, using a more stringent measure of ≥75% SIEF reduction, Kaufman and Chancellor reported observing meaningful differences between the cellular arm and the placebo arm, particularly in the subset of patients (n=75) with prior surgery.

These women had undergone a range of one to five prior SUI surgeries and had a mean duration of symptoms of 12.8 years. Chancellor reported there was a significant improvement among these women who received AMDC-USR, with 40% achieving ≥75% SIEF reduction at 12 months, compared with 16% of patients on placebo.

Significant improvement was also seen in women who underwent AMDC-USR and who had a higher number of stress leaks at baseline, Kaufman said. Among women with >10 stress incontinence episodes (SIEs) at baseline, 39.2% of women in the AMDC-USR group achieved a ≥75% SIEF reduction versus 26.4% of women in the placebo group.

The researchers also found improvements in the AMDC-USR group when using an even more stringent measure of <1 SIE at 12 months (defined as continence restored), with 26.7% of women receiving AMDC-USR restoring continence versus 22.7% on placebo, with the prior surgery arm and those with a greater number of leaks at baseline benefitting the most.

In addition, among those who had greater than a 75% SIEF reduction, the response was durable, with 78.1% remaining responsive at 24 months, Kauffman reported.

“There were very few adverse events that led to discontinuation, and the adverse events related to the study procedures were, in general, anticipated due to the nature of the procedure, such as dysuria for injection or procedural pain for biopsy, Kaufman said. “These were all transient and self-limited.”

In addition, she reported that quality of life and symptom severity scale scores were significantly correlated with changes in SIEF at 12 months in both the AMDC-USR and placebo treatment groups.

Kaufman concluded that the markedly greater percentage of AMDC-USR women with prior surgery and a higher number of stress leaks at baseline who achieved a strong SIEF reduction compared to women on placebo “further supports these populations may be ideally suited for this therapy.”