Mississauga, Canada (January 26, 2022) – Red Leaf Medical (RLM) today announced that results from a multicenter randomized placebo-controlled trial of UROMUNE™, a sublingual vaccine for the prevention of recurrent urinary tract infections in women, were published online in the New England Journal of Medicine Evidence. The results were also recently presented at the American Urology Association meeting (September 2021) and the Canadian Urology Association meeting (June 2021) and showed that UROMUNE™ is effective at preventing and reducing the risk of recurrent urinary tract infections (rUTIs).

Study Design

To determine whether immunization with UROMUNE™ would reduce the risk of recurrent UTIs compared to placebo, a multicenter, prospective, randomized, double-blind, placebo-controlled trial was conducted with 240 subjects (a group of women who had a median of 6 UTIs the previous year) from October 2015 to April 2019. This study included three study arms: subjects were randomly allocated to receive placebo for 6 months or UROMUNE™ for 3 or 6 months, in a 1:1:1 ratio.  All the individuals were followed-up for a total of 12 months from the beginning of treatment.

Study Results

The study found a statistically and clinically important decrease in the incidence of UTI in the vaccinated groups compared to the placebo group (a median number of 3.0 UTIs in the placebo group compared to 0.0 UTIs in the vaccinated group).  There was a significant increase in the UTI-free rate being 56% and 58% in subjects receiving UROMUNE™ (MV140) for 3 or 6 months respectively compared to 25% in the placebo group, in the 9-month follow-up period, post completion of treatment. [i] The study also found the median time to the first UTI post-treatment being of 48 days for the placebo group compared to 275 days for the subjects receiving UROMUNE™ (MV140) for 3 or 6 months respectively.i  The results are comparable to five previous studies published and are similar to preliminary findings in the first North American UROMUNE™ Early Clinical Experience Study conducted in Kingston, Ontario.

Currently, antibiotics remain the only evidence-based recommended treatment for recurrent UTIs and are given for each infection or as continuous daily-dosing prophylaxis. When the patient stops taking antibiotics, however, their UTIs come back with the same frequency they had prior to starting treatment.[ii]

“Uromune is a novel, game changing alternative to antibiotic management of recurrent urinary tract infections in women,” said one of the study’s principal investigators and corresponding author, Dr. J. Curtis Nickel, MD, FRCSC, professor of urology at Queen’s University and Tier 1 Canada research chair in urologic pain and inflammation at Kingston Health Sciences Centre in Canada. “The results of the study represent the future of UTI management and offer the potential to improve antibiotic stewardship and decrease the overall risk of antibiotic resistance.”

Safety

The randomized controlled trial demonstrated that UROMUNE™ has a safety profile comparable to placebo. The most common adverse events (5% or more of participants) were chest infection, candidiasis, and vaginitis. Seven adverse events in five participants were assessed as serious but were determined to be not unexpected or logically related to UROMUNE.

About UTIs

UTIs are one of the most common infections in Canada.[iii] More than 50% of women experience a Urinary Tract Infection (UTI) in their lifetime[iv], with 20% to 40% of those suffering recurrences and requiring multiple short and long-term dosing of antibiotics.[v]  Recurrent UTIs are defined as three or more UTIs during a 12-month period or 2 or more during a 6-month period.ii  UTIs are also the most common infection in older adults and the leading infection requiring antimicrobials in long term care.[vi]

Symptoms of UTIs include a burning feeling when urinating, frequent and intense urges to urinate, pain and pressure in the lower back or abdomen, discolored and strange-smelling urine, and fever or chills. A woman’s daily activities are severely impacted by rUTI and can result in time off employment, with one study noting a mean 1-2 sick days for each acute episode. [vii] A Canadian study noted that women wait up to 5 days before seeking medical attention and had symptoms for a mean of 4.9 days after diagnosis. Sixty-three percent of women with UTIs in the study reported a significant impact on usual activities.[viii]

A woman’s mental well-being is also severely impacted by rUTI. The sudden, unforeseeable and distressing nature of painful UTI episodes often cause patients anxiety.[ix] Mental health scores are reportedly below average in up to 81% of women, regardless of whether the woman is suffering an acute infection or is between infections, and up to 71% of women suffering from rUTI exhibited some degree of depression. vii

The Cost of UTI’s and the Rise of Antimicrobial Resistance (AMR)

The Canadian Council of Academies (CCA) iii estimated that in 2018:

  • Approximately 23.9% of UTIs (1 in 4 patients) in Canada were resistant to antibiotics used to treat them
  • UTIs cost the Canadian health care system approximately 350 million dollars
  • Hospital cost per resistant UTI is approximately 20,000 dollars
  • UTIs were responsible for 6,700 deaths
  • UTIs were responsible for 3,000 years of lost employment
  • Antimicrobial resistance is likely to grow at an alarming rate – from 26% in 2018 to 40% in 2050 costing the healthcare system six to eight billion dollars a year.

Continued use of antibiotics for the treatment or prevention of UTIs not only contributes to the ill health of individual patients, but also to the alarming rise of antibiotic resistance. In Canada, this represents an exorbitant amount of antibiotics — a significant cost and burden to both society and patients. vii

About UROMUNE™

UROMUNE™ is a self-administered vaccine that works by stimulating the immune system, particularly the innate immune system of the bladder. The vaccine is a sublingual spray and the patient administers two sprays under the tongue once daily for three months. UROMUNE™ is composed of four whole cell inactivated bacteria, including equal amounts of UTI-causing pathogens: Escherichia coli; Klebsiella pneumoniae; Proteus vulgaris; and Enterococcus faecalis. UROMUNE™ was developed by Inmunotek, an innovative pharmaceutical company based in Spain. The product is exclusively licensed in Canada to Red Leaf Medical. The company intends to file a new drug submission for UROMUNE™ with Health Canada in the first half of 2022.

About Red Leaf Medical

Red Leaf Medical is a leading Canadian healthcare company specializing in urology and infectious disease. The Company provides innovative therapies and solutions in the areas of pelvic floor health, fertility and urinary tract infections. Red Leaf Medical is a trusted partner to patients and healthcare providers offering industry leading products and patient support programs. Founded in 2009, the company continues to expand its portfolio by launching important new products and services, such as CathetersPLUS™ and ConceptionPLUS™.  Learn more at redleafmedical.com.

[i] Lorenzo-Gomez et al. 2021 AUA abstract “A Novel Sublingual Vaccine Will Dramatically Alter the Clinical Management of Recurrent Urinary Tract Infections in Women” presented by J. Curtis Nickel September 2021.
[ii] Anger J, Lee U, Ackerman AL. Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. J Urol 2019;202:282-289.
[iii] Council of Canadian Academies, 2019. When Antibiotics Fail. Ottawa (ON): The Expert Panel on the Potential Socio-Economic Impacts of Antimicrobial Resistance in Canada, Council of Canadian Academies.
[iv] Foxman B, Barlow R, D’Arcy H, et al. Self-reported incidence of urinary tract infection and associated costs. Ann Epidemiol 2000;10:509-15. https://doi.org/10.1016/S1047-2797(00)00072-7.
[v] Epp A, Larochelle. ASOGC clinical guidelines for rUTI. J Obstet Gynaecol Can 2017;39:e422-31. https://doi.org/10.1016/j.jogc.2017.08.017
[vi] Nicolle, L. (2013). Urinary Tract Infection. In J. F. M. Nunez, J. S. Cameron & D. G. Oreopoulos (Eds.), The Aging Kidney in Health and Disease. London, United Kingdom: Spring Science+Business Media.
[vii] Wagenlehner F, Wullt B, Ballarini S et al: Social and economic burden of recurrent urinary tract infections and quality of life: a patient web-based study (GESPRIT). Expert Rev Pharmacoecon Outcomes Res 2018; 18: 107-117.
[viii] Nickel JC, Lee JC, Grantmyre JE, Polygenis D.  Natural history of urinary tract infection in a primary care environment in Canada.  Can J Urol 12:2728-2737, 2005.
[ix] Renard J, Ballarini S, Mascarenhas T et al. Recurrent lower urinary tract infections have a detrimental effect on patient quality of life: a prospective, observational study. Infect Dis Ther 2015; 4: 125-135.