Clinical Development
Osel has two naturally occurring bacterial strains in clinical development under three investigational new drug applications (INDs). LACTIN-V is a vaginal product that contains a human vaginal strain of Lactobacillus (L. crispatus CTV-05) and is being developed for the treatment of recurrent urinary tract infections (RUTI) and bacterial vaginosis (BV). MIYA-BM is an oral product containing the probiotic bacterium Clostridium butyricum MIYAIRI 588 (CBM 588) that is under development for antibiotic-associated diarrhea (AAD), particularly AAD caused by Clostridium difficile infection (CDI). These three indications are largely caused by abnormal or disrupted microbial flora of the female genitourinary tract or the colon, and are currently treated by antibiotics. Despite successful initial antimicrobial therapy, BV, UTI, and CDI recur at unacceptably high rates and there are presently no adequate treatments to prevent recurrence. Both LACTIN-V and MIYA-BM possess activity against potential pathogens and work to restore normal microbial ecosystems that protect against re-infection by pathogenic microorganisms.
LACTIN-V Clinical Development Plan
Osel successfully completed two Phase I safety trials evaluating LACTIN-V vaginal capsules, one in healthy female volunteers and the other in women with a history of RUTI. The results demonstrated that the product had an excellent safety profile and was well accepted and tolerated by women. Following these initial studies, Osel conducted a randomized, double-blinded, placebo-controlled Phase II trial for the prevention of recurrent BV. This trial continued to demonstrate product safety and acceptability, and suggested potential efficacy in the prevention of BV in women who were effectively colonized with L. crispatus CTV-05. From this study further improvements were made in the product formulation and dosage form to improve the vaginal colonization rates. In 2007-8, a Phase I dose-escalation safety study was conducted in healthy women using the new LACTIN-V formulation in a novel vaginal applicator delivery system, showing that the highest dose of LACTIN-V could be safely delivered by a vaginal applicator. A Phase IIa trial was conducted to evaluate the ability of LACTIN-V delivered with the applicator to vaginally colonize women with BV immediately following treatment with topical metronidazole. This study demonstrated that the efficiency of vaginal colonization, a biologic surrogate of efficacy, was greatly improved using the LACTIN-V applicator as compared to the capsule. In addition, LACTIN-V delivered with the applicator was shown to be safe, well-tolerated and acceptable to the participants. A Phase II trial to evaluate LACTIN-V for the prevention of RUTI was completed recently at the University of Washington. With positive results from the BV colonization trial and the RUTI trial, Osel will be poised to initiate licensure-driven efficacy trials for both indications. Osel enjoys a strategic development advantage that by the nature of Osel's products, and the indications for which they are designed to address, small trials of relatively brief duration will enable a shorter time to market compared to most other products.
MIYA-BM Clinical Development Plan
CBM588 has been safely used in Japan for over 40 years as a non-antibiotic treatment option for conditions characterized by disturbances of the gastrointestinal flora, particularly antibiotic-associated diarrhea (AAD) and Clostridium difficile infections (CDI), as well as irritable bowel syndrome (IBS). Following Osel's in-licensing of this product, a Phase II randomized, double-blinded, placebo-controlled study was undertaken among healthy outpatient adults receiving oral antibiotics to evaluate the safety and potential efficacy of MIYA-BM tablets in preventing AAD. The results showed that the product could be safely used in an American population and suggested a trend for efficacy. Osel recently initiated a Phase II trial to evaluate the safety and therapeutic effect of MIYA-BM fine granules to prevent the recurrence of CDI in hospitalized patients diagnosed with CDI. As the rate and severity of CDI is currently increasing nationwide and accounts for more deaths than all other gastrointestinal infections combined, Osel will vigorously pursue a Phase III efficacy trial and fast-track licensure with the FDA. In addition, Osel is planning to evaluate the therapeutic potential of MIYA-BM for the treatment of IBS.