Vaccine for Recurrent Urinary Tract Infections

Sequoia is developing a vaccine to reduce the recurrences of Urinary Tract Infections (UTI). Sequoia has completed its first clinical study in women with and without a history of recurrent UTI. In this study, Sequoia's investigational vaccine was highly immunogenic and well tolerated.  In addition, it appears that the vaccine may indeed reduce the frequency of UTI.  These preliminary results are from an uncontrolled Phase 1 clinical trial that enrolled 67 women ages 21 to 64.  Of the 67 women enrolled, 30 had a 2-year documented history of recurrent UTI.  Based on these positive Phase 1 results, the vaccine is proceeding to its next human trial.

Because Sequoia’s vaccine is an investigational therapy, its safety and efficacy have not been established.  Sequoia’s vaccine requires additional studies to make any definitive conclusions about safety and efficacy.  Because of the uncertainty of clinical trials, there is no guarantee that Sequoia’s vaccine will become commercially available.  It is not approved by the FDA.

Sequoia’s vaccine consists of the FimH bacterial adhesin protein and a new adjuvant.  There is extensive evidence from more than a dozen laboratories indicating that FimH is essential for E. coli to colonize the bladders of mice and monkeys, and that it enables the formation of intracellular biofilms in bladders.  Moreover, immunization against FimH in a chronic UTI model dramatically reduces the persistence of E. coli in the bladders of mice.  In these chronic UTI experiments, mice first developed a persistent E. coli bladder infection.  They were then immunized against FimH, and a statistically significant reduction in colonized bladders occurred compared to the control group.  Therefore, preclinical research overwhelming supports immunizing recurrent UTI patients against FimH.

Urinary Tract Infections in the United States

There are more than 18 million physician visits for the treatment of UTIs each year in the US, and over 3 million patients experience two or more UTI per year.  For these recurrent UTI patients, antibiotic regimens typically suppress symptoms, but the infections recur within 30 to 90 days.  These patients depend heavily on antibiotics.

A survey of 102 urologists revealed that about 24% of recurrent UTI patients are on suppressive antibiotic regimens consisting of 1-4 months or more of daily antibiotic use.  A separate 57% of recurrent UTI patients self-medicate their symptoms with antibiotic refills. These data demonstrate that approximately 80% of recurrent UTI patients routinely take antibiotics to alleviate their UTI symptoms.  Antibiotics do not reduce recurrences, but only alleviate acute symptoms.

The predominant bacteria causing recurrent UTI are Escherichia coli and Klebsiella pneumoniae.  As of 2012, more than 20% of the Escherichia coli and/or Klebsiella pneumoniae identified from bacterial infections are resistant to all of the antibiotics used to treat recurrent UTI, except for the carbapenems.  And as of 2015, 25% of Klebsiella pneumoniae cultures among patients in a large network of long-term acute care hospitals are resistant to carbapenems.

Resistance to the carbapenems among Klebsiella spp. already exceeds 20% in Italy, Greece, and Romania, strongly suggesting that this resistance will spread throughout the world. The carbapenems are the world’s last line of defense against multidrug-resistant bacteria. Recurrent UTI is an unmet medical need because its treatment is not addressed adequately by antibiotics.  Moreover, reducing the use of antibiotics to treat UTI represents one of the greatest opportunities to reduce antibiotic consumption.