Developing the EU’s first intestinal microbiota-based biologic

Since 2018, biotech company Mikrobiomik has been researching, development and producing innovative biological medicines based on the human microbiome. We are proud to be the first company planning to market MBK-01, the EU’s first biologic based on intestinal microbiota, full spectrum purified intestinal microbiota (FSPIM), in the form of lyophilised capsules for oral administration.

ICD-01 trial results

The Phase III ICD-01 trial results indicate that MBK-01, faecal microbiota transplant (FMT), is effective and safe in the treatment of Clostridioides difficile infection (CDI). This randomised, open label-controlled multicentre clinical trial was conducted across 21 sites in Spain from 2021 to 2023.

The study included 92 adult patients with confirmed CDI. The main objective was to evaluate the efficacy and safety of MBK-01 compared to fidaxomicin, providing significant insights into the potential of MBK-01 as a treatment for primary or recurrent CDI and contributing to the advancement of microbiome-based therapies.

Participants were randomly assigned in a 1:1 ratio to the control group receiving fidaxomicin at 200mg every 12 hours for 10 days (47 patients), or the experimental group receiving MBK-01 (45 patients), consisting of four lyophilised capsules of heterologous faecal microbiota administered orally on an empty stomach. Donor of stools for MBK-01 were screened for pathogens and viruses to ensure safety. After treatment, patients were followed up at intervals of 72 hours, three weeks, eight weeks, three months and six months.

Efficacy and safety outcomes of MBK-01

The primary efficacy outcome was the absence of Clostridioides difficile (CD) diarrhoea recurrences without the need for retreatment within eight weeks post-treatment.

Secondary efficacy outcomes included time to recurrence, overall survival, and clinical outcomes (favourable/unfavourable). Safety and quality of life of the patients participating in the study were also assessed.

MBK-01 demonstrated a greater clinical benefit than fidaxomicin when used as the first choice for treatment of the current CDI episode event without any antibiotic treatment.

For recurrent CDI, MBK-01 showed superior efficacy, despite current guidelines recommending FMT only in cases of multiple recurrences.^1-3 This is supported by the increasing probability of recurrence with further CDI episodes and antibiotic treatment.^4,5

Further findings for MBK-01

In this study, considering the general population, 10.81 percent of patients treated with MBK-01 experienced CDI recurrence compared to 22.5 percent of those treated with fidaxomicin. By subgroups, the recurrence rate for MBK-01 was significantly lower than for fidaxomicin in recurrent CDI cases, with only 18.75 percent compared to 61.54 percent for fidaxomicin, positioning MBK-01 as a superior therapeutic alternative.

Conversely, the treatment of primary CDI events with FMT was an innovative aspect of this trial, with MBK-01 showing non-inferiority to fidaxomicin and aligning with previous studies.^6,7 In the analysis of prior antibiotic treatment use, the data suggest a loss of efficacy in both treatment groups as the number of antibiotic treatment lines increases, which is more significant in the case of fidaxomicin than in that of MBK-01.

Additionally, MBK-01 did not increase the frequency of adverse events (AEs) commonly associated with CDI or antibiotic treatment and was well tolerated. Adverse events were relatively low in both groups (2.22 percent for MBK-01 and 4.26 percent for fidaxomicin). The specific representation of these events differed between the treatments, highlighting potential differences in side effect profiles that should be explored in further studies. Thus, these data suggest MBK-01 is a safe and well-tolerated treatment.

Advantages of MBK-01 over common alternatives

Common alternatives for CDI treatment include fidaxomicin, vancomycin and metronidazole, but resistance to these antibiotics is a major concern.⁸ In this scenario, MBK-01, a microbiota-based therapy, has been shown to be non-inferior to fidaxomicin in primary cases and superior in efficacy in recurrences. This implies indirect benefits in reducing antibiotic usage, which in turn has financial implications for lowering the annual healthcare cost associated with CDI in Europe.

MBK-01 has several advantages over fidaxomicin: it is administered in a single dose and is orally administered, making it less invasive. However, statistical comparison was limited due to the low probability of recurrence in both treatment groups and the sample size.

In summary, MBK-01 provides greater clinical benefit compared to fidaxomicin when employed as the primary treatment option for both primary and recurrent episodes of CDI, even in cases where no prior antibiotic treatment was used.

In primary episodes, MBK-01 demonstrates non-inferiority to fidaxomicin, potentially reducing the need for antibiotics, while for recurrent infection, MBK-01 shows superior efficacy over fidaxomicin. Overall, MBK-01 has potential to be an effective, easy-to-administer, low-risk treatment for CDI.

Future prospects

Anticipating a positive Phase III outcome and a potential commercial launch in 2025, we aim to capture a substantial share of the market for primary and recurrent CDI patients, marking a turning point in the management of this condition.

References

1. van Prehn J, Reigadas E, Vogelzang EH, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021; 27 (2): S1-S21.
2. McDonald CL, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66: 987–94.
3. Trubiano JA, Cheng AC, Korman TM, et al. Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand. Intern Med J. 2016; 46: 479–93.
4. CP Kelly. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012; 18 (6): 21-27.
5. Song JH, Kim YS. Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention. Gut Liver. 2019; 13(1):16-24..
6. Hocquart M, Lagier JC, Cassir N, et al. Early Fecal Microbiota Transplantation Improves Survival in Severe Clostridium difficile Infections. Clin Infect Dis. 2018; 66(5): 645–50.
7. Baunwall SMD, Andreasen SE, Hansen MM, et al. Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2022; 7(12):1083-1091.
8. Peng Z, Jin D, Kim HB, et al. Update on Antimicrobial Resistance in Clostridium difficile: Resistance Mechanisms and Antimicrobial Susceptibility Testing. J Clin Microbiol. 2017; 55(7):1998-2008.