Current treatments for Bacterial Vaginosis, a condition caused by a disturbed vaginal microbiota resulting in certain bacteria becoming overgrown, comprise of antibiotics – tablets, gels, or creams. Antibiotics work by killing the overgrown bacteria to restore community balance. However, given the non-precise nature of antibiotics, re-balancing the microbiota is not always achieved and up to 80% of cases will recur within 9 months of effective treatment.1 Moreover, oral antibiotics potentially disrupt the gut microbiome.2
At the inaugural Microbiome Times “Microbes in Women’s Health Congress” – Copenhagen, April 9, 10 & 11 2024 – Ravel, Mitchell, and Biose’s CEO Adrien Nivoliez presented their work in taking a novel treatment from concept to the clinic, with a talk entitled “MGH and Biose Industrie: The Clinical Journey of a Multi-Strain LBP“.
The trio described the development of two multi-strain consortium LBPs targeting BV, LC106 and LC115. Both drug products contain multiple strains of L. Crispatus, 6 strains and 15 strains respectively, identified in women with a very stable vaginal microbiota. The presentation covered various considerations for design, formulation, regulation, and manufacture in developing this novel programs.
“You actually could potentially maximise the colonisation, they might not all colonise but maybe some strain will colonise in some women and others in others”
Ravel said on the benefits of a multi-strain approach compared to a single strain one.
Mitchell detailed the team’s discussions with the FDA, outlining the differing expectations of the regulatory agency across phases. Regarding the level of strain characterisation expected in phase 1
“they said fine you can do just culture on the total viable CFU count per dose that’s fine for now.” But for later stages the team “are going to need to show us individual strain by strain viability and stability over time.”
Biose Industrie were selected to manufacture the two programs in early 2022 and have since developed the candidates to GMP clinical scale. Nivoliez described this journey in detail, beginning with a risk assessment and research cell banking of the strains in early 2022 and leading to a regulatory support master file filing in July 2023, for the programs to enter the clinic.
As well as highlighting Biose’s work to scale the programs, from 2L scale to 150L, Adrien discussed how Biose achieved temperature stability for LC106 and LC115. With Biose’s inhouse expertise resulting in both candidates maintaining a stable dose of 2×10^9 CFU/tablet dose at temperatures ranging from 5°C to 25 °C.
Adrien also described Biose’s work to optimise the placebo formulation to eliminate any influence on the trials results. Biose tested placebo formulations with various colour and disintegration properties to achieve the perfect placebo for clinical testing. Resulting in a placebo that appeared and superficially behaved in the same way as the real drug products.
The two products are currently in phase 1 with patient recruitment in both the US and South Africa, the estimated study completion date is September 2024.
Citations:
- Cook, R.L. et al. (1992) ‘Clinical, microbiological, and biochemical factors in recurrent bacterial vaginosis’, Journal of Clinical Microbiology, 30(4), pp. 870–877. doi:10.1128/jcm.30.4.870-877.1992.
- Willing, B.P., Russell, S.L. and Finlay, B.B. (2011) ‘Shifting the balance: Antibiotic effects on host–microbiota mutualism’, Nature Reviews Microbiology, 9(4), pp. 233–243. doi:10.1038/nrmicro2536.