Unmet Medical Needs
Diseases of the female urogenital tract:
The healthy female urogenital tract is densely populated with commensal bacteria, primarily certain
Lactobacillus species, that play an important role in protecting the host from infection. Disruption of the
Lactobacillus-dominated microbial flora can lead to abnormal vaginal microbial communities associated with bacterial vaginosis (BV), and an increased incidence of urinary tract infection (UTI). In addition, epidemiological studies suggest that the normal vaginal microbial ecosystem may play a critical role in reducing the risk of sexually transmitted infections, including human immunodeficiency virus type 1 (HIV-1). These observations have provided the rationale for using appropriate
Lactobacillus species to reduce the risk of infection by preserving or restoring the normal vaginal microflora. Our lead product candidate, LACTIN-V vaginal capsule, contains the lactic acid and hydrogen peroxide producing bacterium Lactobacillus crispatus, a naturally occurring member of the protective urogenital microflora.
UTIs account for almost 11 million physician visits each year in the US, and an equal number in Europe. Up to 33% of women with UTIs develop recurrent infections (>2 per year). While a routine UTI is easily treated with a short course of oral antibiotics, treatment of recurrent UTI (RUTI) with multiple courses of antibiotics may lead to resistant strains, diarrhea, and vaginal yeast infections. Thus, there is significant interest amongst women who suffer from RUTI for novel non-antibiotic therapies. Bacterial Vaginosis (BV) afflicts over 16 million women every year worldwide, with 50% experiencing recurrent infections, and is the most common reason that women seek medical help, after vaginal yeast infections. It is expected that this product will treat and prevent recurrences of both UTI and BV. Finally, in vitro fertilization (IVF) remains a challenging problem with successful embryo transplantation occurring in only 30% of IVF procedures. Osel’s lead product, Lactin-V, offers the potential to prevent recurrences of both UTI and BV and to markedly improve the success rate of embryo implants in women undergoing IVF procedures.
Diseases of the gastrointestinal tract:
One of the most common side effects of antibiotic therapy is disruption of the protective intestinal microflora, resulting in diarrhea. The incidence of antibiotic associated diarrhea (AAD) varies widely and can range up to 30% of all hospitalized patients. The symptoms of AAD can vary from slight abdominal discomfort to severe diarrhea and fulminant colitis. The impact of AAD is reflected by longer hospital stays, higher medical costs, and increased rates of comorbidity.
The gut microflora normally contributes importantly to fermentative processes of the gut and colonization resistance to pathogenic organisms. Disruption of the gut microflora by antibiotics may lead to disturbances in carbohydrate and bile acid metabolism, reduced short chain fatty acid production, and functional disturbances of the intestinal mucosa, resulting in osmotic or secretory diarrhea. Disruption of the complex intestinal ecosystem also reduces colonization resistance and can lead to the emergence and overgrowth of enteric pathogens, most importantly Clostridium difficile.
AAD can be divided into two major types with different etiologies: uncomplicated or non-specific diarrhea (not associated with Clostridium difficile) and C. difficile-associated diarrhea and colitis. Uncomplicated AAD is usually a self-limited, nonprogressive illness without intestinal lesions. Typically no pathogens are detected and the diarrhea is largely due to changes in the composition and function of the intestinal microflora caused by the antibiotic. Most patients respond to non-specific supportive care, fluid and electrolyte replacement, and discontinuation of the offending antibiotic. C. difficile accounts for about 20% of all AAD cases, and represents the most common intestinal infection in the hospital setting. This organism is much more prevalent in AAD cases with evidence of colitis, and is present in virtually all cases of pseudomembranous colitis, the most severe form of AAD. The clinical manifestations of C. difficile-associated disease (CDAD) are mediated by two toxins elaborated by toxigenic strains of the bacterium. Metronidazole is currently the drug of choice for the initial treatment of CDAD, with vancomycin reserved for more seriously ill patients, due to the emergence of vancomycin-resistant enterococci and Staphylococcus aureus in hospitals. Although initial response rates of >90% have been reported for these drugs, CDAD typically relapses at an unacceptably high rate of about 20%. Of patients experiencing a relapse, greater than half will go on to have additional recurrences of infection. Patients with relapsing CDAD often develop the most severe disease and represent a therapeutic challenge since the antibiotics used to treat the disease promote the continued disruption of the intestinal microflora. There are at present no effective non-antibiotic treatments for preventing the recurrence of CDAD. Our recently in-licensed product, CDACTIN-O oral tablet, contains a non-pathogenic, butyric acid producing strain of Clostridium butyricum that has been safely used in Japan for over thirty years as a non-antibiotic treatment option for AAD. CDACTIN-O may reduce the incidence and severity of AAD by promoting restoration of the normal intestinal microflora and colonic mucosa function through the elaboration of short chain fatty acids, while antagonizing the growth of enteric pathogens.
CDACTIN-O offers the potential to prevent AAD and CDAD, thereby reducing extended hospital stays, enabling patients to complete their antibiotic regimens with fewer adverse side effects and potentially eliminate the serious complications of CDAD.
