Disorders of the Urogenital
and Reproductive Tracts
Antibiotics are used to treat urogenital infections, but recurrences are common. Antibiotics inhibit or kill the bacteria that cause these infections, but and they do not prevent recurrence of infection since they do not restore protective Lactobacillus. To address this unmet medical need, Osel developed a proprietary Live Biotherapeutic Product (LBP), called LACTIN-V that contains the protective vaginal strain Lactobacillus crispatus CTV-05. L. crispatus CTV-05 produces lactic acid and hydrogen peroxide, adheres to vaginal epithelial cells, and antagonizes bacteria associated with BV and uropathogenic E. coli, which is responsible for most UTIs.
Bacterial vaginosis (BV) is a common condition in women that accounts for up to 25% of visits to gynecologic clinics in the U.S. and afflicts over 16 million women every year worldwide. The estimated annual global economic burden of treating symptomatic BV is US $4.8M. The US economic burden of BV is nearly tripled when including costs of BV-associated preterm births and human immunodeficiency virus cases. BV is characterized as an ecological disorder or dysbiosis of the vaginal microbiome. In BV, certain Lactobacillus species, particularly hydrogen peroxide-producing strains, are depleted and replaced with largely anaerobic organisms that can cause an unpleasant “fishy” odor, a burning or itching sensation, abnormal vaginal discharge, and underlying inflammation. BV is a risk factor for pre-term labor, post-caesarean section infections, and sexually transmitted infections, including HIV. BV is treated with oral or topical antibiotics to kill BV-associated bacteria, but up to 75% of women can experience recurrent infections, in part because dysbiosis can persist in many women following antibiotic treatment. Currently there are no approved therapies available to prevent BV recurrence other than prophylactic antibiotics.
Recurrent Urinary Tract Infection
Preterm birth (PTB), delivery prior to completion of 37 weeks of gestation, is the greatest challenge facing obstetrics in the modern era. It is the world’s leading cause of childhood mortality and is associated with 80% of all neonatal morbidity resulting in major financial and emotional cost to families and society. In 2007, the Institute of Medicine reported that the cost associated with premature birth in the United States was $26.2 billion each year. The preterm birth rate in the US was 10.1% in 2021, over 360,000 PTBs. PTB has several well-established risk factors including a history of PTB, PPROM, large loop excision of the transformation zone of the cervix (LLETZ), cone biopsy, mid-trimester loss (>16 weeks), short cervix (<25mm) in a previous pregnancy, Caesarean section at full cervical dilatation, trachelectomy, previous cervical tear or congenital uterine anomaly. Bacterial vaginosis is also a known risk factor for PTB.
In pregnancy, vaginal communities depleted in Lactobacillus species are associated with increased risk of preterm pre-labor rupture of the fetal membranes (PPROM) and PTB. Conversely Lactobacillus dominance, particularly by Lactobacillus crispatus, has been shown to be protective of PTB. Other than progesterone and cervical cerclage, there are no treatments to prevent PTB. A Phase 1 study of LACTIN-V in pregnant women at high risk of PTB was recently completed (NCT03992534).