In this interview, Melissa R. Kaufman, MD, PhD, FACS, describes the promise of a regenerative approach to treating recurrent incontinence in women known as autologous muscle derived cells for urinary sphincter repair (AMDC-USR).
Stress urinary incontinence is a consistent health issue in female patients that is typically treated with surgical interventions. Clinicians have investigated less invasive treatments for this debilitating condition, but the question is whether they are safe and produce positive results.
In a recent study presented at the 2021 American Urological Association Annual Meeting, Melissa R. Kaufman, MD, PhD, FACS, and colleagues assess how the AMDC-USR technology mitigates primary SUI symptoms. Kaufman is a professor of urology and chief of the division of reconstructive urology and pelvic health at Vanderbilt University, Nashville, Tennessee.
This technology is truly a transformational opportunity for urology. This is the first regenerative option that's undergone such rigorous clinical evaluation. AMDC stands for autologous muscle derived cells and it's a product of muscle progenitor cells, which are stem cells that reside within the skeletal muscle that are stimulated by injury. These are terminally differentiated cells, and they originate from the biopsy that we harvest and the vastus lateralis of the thigh. They're grown in culture and then re-injected into the urethral sphincter and theorized to engraft to improve muscle function of the sphincter muscle that's causing the stress incontinence secondary to many of the sub quality of aging and prior surgeries. This product is in clinical trials for multiple interventions.
The one that we are discussing at this year's AUA is for stress urinary incontinence in women, but we also envision this being a product that can be used for men after prostatectomy; for fecal incontinence, in which there's ongoing studies; for under-active bladder, which is a very profound problem ranging across many areas; as well as for tongue dysphasia. The product that we're going to be discussing at AUA is developed for women with primary symptoms of stress incontinence. It's our most studied clinical indication. We've had over 600 women treated across the world since the initiation over a decade ago in our phase 1 and phase 2 trials. We're now embarking on our third phase 3 study. The AMDC product augments the urethral sphincter function that is deficient in women with stress incontinence, and as such, may serve as a really durable treatment for decades of time, maybe amenable to retreatment for a number of women. The product causes localized tissue changes that may engraft into the muscle and may cause a paracrine effect to bring in new growth factors. It may stimulate the progenitor cells that are there. In the studies that are presented at the AUA, one of the most interesting populations is a group of 115 women that were pooled across a number of studies that had prior surgeries for stress incontinence yet had recurrent or persistent symptoms following those surgeries. This is a population that have a life-altering condition who have already embarked upon prior surgeries and have very limited treatment options.
We all know that stress incontinence has an enormous impact on women's quality of life, and that ranges well beyond the direct symptoms that can be caused by pad use. It increases women's risk for depression, anxiety, decreased physical activity, productivity, and their daily activities at work. They suffer in healthy social and sexual relationships, and their day-to-day function really diminishes. When we look at that population have recurrent or persistent incontinence, these are women that progress in severity over time. What we found is that they had a higher level of bother on all our validated questionnaires to start with, because they had already embarked upon surgical therapies of which we all understand the pitfalls of. So, they have very limited treatment options and the adult muscle derived cells for sphincter regeneration represent a non-surgical means to provide very durable and effective support for these women who have suffered mightily from stress incontinence, oftentimes for long periods of time. They have not responded to what we would consider "gold standard" therapies for treatment.
We assume and hypothesize about what our outcomes are going to be in clinical trials, but interestingly, we've known from a lot of prior trials, both in this technology space for adult muscle derived cells and other stem cells and other incontinence measures, that determining the optimal levels of efficacy to discriminate well between your active agent versus placebo is a very complex endeavor. It's because I believe what happens is that women are now aware of their condition, and a clinical trial, sometimes there's mitigation and moderation of behaviors, so those conservative impacts are very powerful and we know that. They're often frontline therapies for both urgency and stress incontinence, so our placebo rates tend to be higher. That wasn't necessarily surprising in this trial, but what was novel was the remarkable efficacy in women who've undergone prior surgery with up to 30% demonstrating 0 to 1 stress leaks on their diaries. These were women that on their 3-day diaries, overall, had an average of 18 stress leaks. They could be between 3 and 45 to enroll in the trial, so to have 30% end up with what we would consider "cured situation" was very profound. It was quite a phenomenal success.
There's a group of women who have persistent recurrent incontinence following prior surgical interventions. This is truly an unmet medical need. These symptoms substantially impact daily functioning, impact quality of life. This is a well-tolerated outpatient procedure with excellent safety parameters. It is a single biopsy and a single injection, both of which take minutes of time. It is effective in this really challenging refractory population. And based on that evidence, data was submitted to the FDA because of the seriousness of this condition and Cook MyoSite was granted a regenerative medicine advanced therapy designation. This is a very powerful statement about not just the technology, but also this unmet need for our patients.
We are currently engaged in undertaking a phase 3 randomized placebo-controlled trial, which will be the third in the series for data presentation to the FDA to further define the technology and really optimize the population that responds best for treatment. We anticipated enrolling almost 300 women again. Almost 600 women today have engaged in these trials already, so this will be 300 more patients who will help all the women benefit from the technology and the future.
We are truly embarking at this moment on the next frontier in urology with these types of cellular therapies. It is an exceptionally gratifying opportunity to be able to potentially provide durable, safe treatments that actually reverse pathology and regenerate native function. The potential applications for this technology are very broad. The next decades of innovations in this space are going to be astounding and transformative to our current treatment strategies, and impact countless urology patients to really improve not just quality of life, but also quantity of life.
1. Kaufman MR, Peters KM, Chermansky CJ, et al. A double-blind, randomized, controlled trial comparing safety and efficacy of autologous muscle derived cells for urinary sphincter repair (AMDC-USR) with placebo (PBO) in women with stress urinary incontinence (SUI). Paper presented at 2021 American Urological Association Annual Meeting; September 10-13; virtual. Abstract PD06-01