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Women who suffer from recurrent urinary tract infections (rUTIs) are typically treated with antibiotics. These treatment regimens, however, are associated with high rates of morbidity as the world faces rising antibiotic resistance.
In a recent study, “A novel sublingual vaccine will dramatically alter the clinical management of recurrent urinary tract infections in women,” presented at the 2021 AUA annual meeting, J. Curtis Nickel, MD, and a team of investigators found that the novel MV140 vaccine is a safe and effective strategy for treating rUTI in women.1 Nickel is a professor in the department of urology at Queen’s University and a urologist at Kingston and Hotel Dieu General Hospitals, Kingston, Ontario, Canada.
According to Nickel and his coinvestigators, MV140 is a polybacterial sublingual vaccine, consisting of E. coli, K. pneumoniae, E. faecalis and P. vulgaris, which induces a T-cell specific adaptive and an immune response at the genitourinary tract.
The findings shared at the AUA meeting included results from early uncontrolled studies, the first phase 3 multicenter, double-blind, placebo-controlled randomized controlled trial (RCT), ongoing safety monitoring from special access programs (SAP; 2014-2020), and the first North America (NA) clinical experience evaluating MV140 (Uromune) for the prevention of rUTI in women.
Across 5 uncontrolled studies, results found that 1408 women treated with MV140 had significantly higher UTI-free rates (35% to 90%) compared to 499 women treated with antibiotics (0% to 9%). Additionally, the RCT revealed UTI-free rates of 55.7% at 3 months and 58.0% at 6 months, while the placebo group exhibited a rate of 25%. The median number of UTIs in MV140-treated patients within this study were 0.0 (IQR, 0.0-1.0), compared to 3.0 for placebo patients (IQR, 0.5-6.0).
As for the ongoing SAP study, only 1.7% of over 20,500 patients reported adverse reactions. And in the NA study, patients experienced a 48% UTI-free rate with an overall 82% reduction in UTI episodes. Only 1 patient had 2 mild vaccine-related adverse reactions in this study.
Taken as a whole, these findings suggest a potential, evidence-based alternative to standard antibiotic regimens in treating patients with rUTI.
Recurrent urinary tract infections in women are a major health care issue. It's not really associated with mortality; it's associated with a lot of morbidity. With more than half of women having a UTI sometime in their life, about 40% of them will be classified as having recurrent urinary tract infections. That's more than 3 per year, and for many that can be, on average, about 6 a year. So, 3 out of 100 women every year are classified of having recurrent urinary tract infections.
The way we manage those are using things like cranberry extract, probiotics, and certainly intervaginal estrogen for perimenopausal and postmenopausal women. But the only treatment that's really effective is antibiotics—either episodic antibiotics or long-term prophylactic antibiotics that are taken for weeks and months. The antibiotics themselves are problematic. There is cost to patient and society, there is the detrimental effect of antibiotics on the patient with adverse events or effects, sometimes being quite serious and even irreversible. Antibiotics only work as long as the patient is taking the antibiotic. And then we have the rising spectra of national and international antibiotic resistance, which is becoming a huge international medical issue.
Right now, there is a huge unmet need in women's health for some way to prevent recurrent urinary tract infections. I mentioned the methods that we have, and the only one that really works well is intervaginal estrogen in peri- and postmenopausal women, but it doesn't work in all. We discussed the problems associated with antibiotics. So, what we're looking for is some safe and effective intervention that will completely change the way we manage recurrent urinary tract infections in women. I and others have always believed that the answer would be a vaccine. Over the last 20 years we've looked at vaccines, and there are vaccines available with some efficacy, but not enough to change the game from antibiotics to something safer and more effective. That's why I think this vaccine, with its effectiveness and safety, will be a major game changer.
I am always surprised when a large, well-planned, randomized, placebo-controlled trial is positive or even more positive than we thought with early observational, uncontrolled studies. And we do have evidence from at least 5 studies that this sublingual vaccine is effective and safe. I have the only early clinical experience in North America, having had over 65 patients vaccinated and having followed them, some for over a year. So, I know the vaccine works. But we're always wondering whether or not it would show in a randomized, placebo-controlled study and this study met and exceeded the endpoint in reducing the risk and preventing urinary tract infections.
In this particular study, we were able to show that there was a very clinically significant decrease in the rate of UTIs in the vaccinated group, preventing UTIs in almost 60% of vaccinated patients. We found that if patients did get a UTI, and there was a significant median time to UTI that was many times greater in the vaccinated group, it was usually mild and self-limited. The study went for 9 months. Based on real world experience with this vaccine in special access programs outside North America, we believe that the vaccine efficacy may wear out after a year or 2. So, future studies are going to have to look at re-vaccinating patients who revert back to their recurrent urinary tract infection state.
Further, there is some evidence in observational studies that's effective and complicated, showing outcomes for UTIs in the frail elderly, in children and in men, we're going to have to look at all those groups. This could be a game-changer for recurrent urinary tract infections in children who rely on antibiotics. It could be a game changer in the frail elderly, particularly those in long-term care homes, where UTIs are a significant problem, even causing mortality and antibiotic over utilization. We'd also like to see it used in complicated UTIs in men. All these are going to have to be studied, and that's why it's so exciting. This vaccine has legs to run on.
The take-home message for international urologists is that this vaccine is available on named patient programs or special access programs. Unfortunately, that's not the case for North America. Health Canada realizes the huge unmet need and is going to be looking at regulatory approval on an expedited basis based on the observation studies, the special access program safety audit on over 20,000 patients have already received this, the Canadian early experienced trial that we're doing and the RCT. We may have approval in Canada for this vaccine for Canadian women with recurrent UTIs sometime next year. The FDA is going to probably look at this data and advise whether or not further studies will be required in the United States before it's widely available in the United States either under special access programs, or across the board. It'll take a little time in the United States. Vaccines are a little more problematic in United States compared to the rest of the world.
It's exciting research. The randomized, placebo-controlled study has replicated all the previous studies, looking at recurrent urinary tract infections and this vaccine. The other thing they should realize is that it is a vaccine that is self-administered by the patient sublingual over 3 months. That is why it appears to be so safe. It's not an injected vaccine. The immunity builds up very slowly over 3 months, and it persists for 9 months. We'll see how long that durability effect is over the long term, but keep your eyes and ears open because, like I said, this vaccine will be a game changer for women's health in the future.
1. Nickel JC, Lorenzo-Gómez MF, Foley S, Saz-Leal P. A novel sublingual vaccine will dramatically alter the clinical management of recurrent urinary tract infections in women. Paper presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PLLBA-02.