On May 14, 2020, a team spanning the University of California San Diego, San Francisco General Hospital, Cook County Health and Hospitals System in Chicago, and Washington University in St. Louis published a milestone study in the New England Journal of Medicine. Cohen et al demonstrated the effectiveness of LACTIN-V, a new Live Biotherapeutic Product (LBP) created by Osel, Inc. for the treatment of bacterial vaginosis (BV).
LACTIN-V is a single-strain, topically-administered LBP containing Lactobacillus crispatus CTV-05, a protective human vaginal bacterium that helps to combat the pathogenic bacteria and dysbiosis observed in recurrent BV and urinary tract infections. Its success marks the first single-strain LBP to show clinically significant efficacy in a randomized, double-blind, placebo-controlled Phase 2b trial in the US.
The study was supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). List Labs is excited by this landmark discovery, by the prospects of this discovery for women’s health around the world, and for further supporting the use of LBPs as a viable therapeutic. We had a chat with Osel’s Director of Product Development, Tom Parks, to find out more about the project, it’s challenges, and why the product is successful:
What are dysbiosis and BV?
Dysbiosis is a disruption of the human microbiome: the collection of microorganisms, including bacteria, that naturally live on and in our bodies. The full function of the microbiome isn’t fully understood, but dysbiosis is known to be involved in a wide range of skin disorders, intestinal problems and gum diseases, among many others.
Bacterial vaginosis is an ecological disorder of the vaginal microbiota in which hydrogen peroxide-producing lactobacilli are displaced by predominantly anaerobic bacteria (e.g. Prevotella and Mobiluncus species), Gardnerella vaginalis, and Atopium vaginae. It is the most common vaginal infection worldwide among women of reproductive age, and affects about 30% of women in the US. Treatment usually consists of a course of an antibiotic such as metronidazole lasting about five days. The treatment itself is usually effective, but in about 75% of cases BV returns within a year, often within just a few weeks.
Why is treating BV so challenging?
The tendency of BV to recur is due to failure to re-establish a Lactobacillus-dominated vaginal microbiome. Since the only treatment is another course of metronidazole or a similar antibiotic, this can lead to a cycle of re-infection. In addition to the discomfort and negative impact on the quality of life, BV is a risk factor for a wide range of sexually transmitted infections, including HIV/AIDS. It is also a risk factor for premature birth and other reproductive health complications.
Currently there is no approved treatment to prevent the recurrence of BV. Women have tried a range of home remedies, from yogurt to tea tree oil. As might be expected, these are often ineffective, and may have side effects of their own.
Osel has developed a treatment for BV that breaks the cycle of dysbiosis. LACTIN-V is a live biotherapeutic product (LBP) containing the hydrogen peroxide-producing strain Lactobacillus crispatus CTV-05, which is a protective member of the native microbiome. Administered after the normal course of antibiotics (once a day for five days, and then twice a week for 10 weeks), LACTIN-V helps to restore the normal vaginal environment and prevent re-emergence of the organisms that cause BV. In the study reported in NEJM, BV recurrence was significantly less in women treated with Lactin-V (30%) compared to the placebo group (45%) (P=0.01).
What goes into manufacturing an LBP?
An LBP is a therapeutic agent based around a live microorganism, intended to restore a balance in the microbiome disrupted by a disease condition. A contract development and manufacturing organization (CDMO) can provide essential expertise for developing an LBP, but finding the right CDMO is tricky since many contract manufacturing organizations do not have experience with maintaining viability of the microorganism through the entire manufacturing process or are flexible for the process nuances of an LBP product. In addition, many organisms of interest as LBPs are anaerobic to some extent (for example, Lactobacillus are facultative anaerobes), and/or spore-forming. Working with such organisms takes special expertise and facilities to provide necessary containment and segregation, maintain viability, maximize yield, and avoid pitfalls.
Osel’s Tom Parks explains, “Relevant live biologic product experience and GMP manufacturing capabilities are obviously important. Flexibility to handle a number of product formats is also helpful. Since the field is relatively new, companies that manufacture LBPs are few and far between.”
Are you looking for a CDMO for your LBP project? List Labs has 40 years of experience manufacturing bacterial products and many different LBP products for Phase 1 and 2 clinical trials for indications in the gut, skin, vaginal mucosa, and CNS. List Labs has the expertise for handling and cultivating anaerobic bacteria and spore formers. We are uniquely qualified to provide insight and the flexibility to match the needs and requirements of each individual project, such as filling different product formats. We are a passionate and dedicated partner who works as an extension of your team to ensure the success of your project. If you are interested in an LBP project, contact us at firstname.lastname@example.org