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MH002, AN OPTIMIZED LIVE BIOTHERAPEUTIC PRODUCT, PROVIDES EFFICACY IN ACUTE POUCHITIS: RESULTS FROM A PILOT STUDY

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MH002, AN OPTIMIZED LIVE BIOTHERAPEUTIC PRODUCT, PROVIDES EFFICACY IN ACUTE POUCHITIS: RESULTS FROM A PILOT STUDY

Severine Vermeire 1, Pieter Dewint 2, Triana Lobaton Ortega 3, Mariangela Allocca 4, Franco Scaldaferri 5, Sam Possemiers 6, Ludo Haazen 6, Selin Bolca 6

Affiliations

1 University Hospital Leuven, Leuven, Belgium

2 AZ Maria Middelares, Ghent, Belgium

3 GHENT UNIVERSITY HOSPITAL, Gent, Belgium

4 IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Milano, Italy

5 Catholic University of Rome Dept. of Internal Medicine Dept. of Gastroenterology, Roma, Italy|||Fondazione Policlinico A. Gemelli IRCCS, Italy, Rome, Italy

6 MRM Health, Ghent, Belgium

Summary

AI Generated

In this open-label pilot study of 13 patients with acute pouchitis, 8 weeks of treatment with MH002, a consortium of 6 commensal bacteria, achieved modified PDAI remission in 46% and was safe and well tolerated with no adverse reactions.

At week 8, 6/13 (46%) subjects achieved mPDAI remission, defined as mPDAI less than 5 and a reduction of at least 2 points from baseline
Symptomatic response, endoscopic response, and histologic response were achieved in 5/13 (39%), 5/13 (39%), and 2/13 (15%) subjects, respectively
In the subgroup achieving remission, median faecal calprotectin decreased by 68%, 71%, and 80% at weeks 2, 4, and 8, respectively
MH002 was safe and well tolerated with no adverse reactions; two serious adverse events (hypertension and perianal abscess) were unlikely drug-related
Improvement in severity of urgency was reported by 8/13 (62%) subjects at week 8, and Robarts Histopathologic Index improved in 9/13 (69%) subjects
The authors conclude these results warrant further development of MH002 in a phase 2/3 study for acute pouchitis, a condition with no currently approved treatment

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Abstract

Introduction

Pouchitis is an inflammatory disease of the pouch in patients with ulcerative colitis who underwent total colectomy with ileoanal pouch anastomosis. There is no approved treatment for acute pouchitis at present. First-line treatment consists of antibiotics or probiotics. MH002 is an optimized consortium of 6 non-pathogenic, well characterized commensal bacteria with immune modulating, wound healing and gut barrier protective effects, and is in clinical development for ulcerative colitis.

Aims & Methods

This multi-center, open-label pilot study (EudraCT 2021-006656-14) explored the efficacy and mechanistic effects of MH002 in acute pouchitis. Eligible subjects with a modified pouchitis disease activity index (mPDAI) ≥5 and mPDAI endoscopic score ≥2 and with symptoms lasting ≤4wks, received 400mg MH002 once daily for 8wks. Clinical, biochemical, endoscopic, and histologic disease activity was assessed at baseline and wk8. Pouch biopsies were assessed by an IBD pathologist who was blinded to the time points and clinical outcomes. Exploratory efficacy endpoints (N=13) included mPDAI remission (mPDAI<5 and a reduction of ≥2 points from baseline), symptomatic response (a reduction of clinical PDAI≥2 points), endoscopic response (a reduction of endoscopic score of ≥2 points), and histologic response (a reduction of histologic PDAI≥2) at wk8. Changes from baseline in severity of urgency (NURS), Robart’s histopathologic index (RHI), and faecal calprotectin (FCP) concentrations, were also evaluated.

Results

MH002 was safe and well tolerated with no evidence of adverse reactions when administered for 8wks (Abstract Vermeire et al.). At wk8, 6/13 (46%) subjects achieved mPDAI remission. Symptomatic, endoscopic, and histologic response rates were 5/13 (39%), 5/13 (39%), and 2/13 (15%), respectively. Clinical, endoscopic, and histologic PDAI scores were improved at wk8 in 11/13 (85%), 7/13 (54%), and 3/13 (23%) subjects, respectively. In total, 8/13 (62%), 9/13 (69%), and 8/13 (62%) subjects reported an improvement in severity of urgency at wk2, wk4, and wk8, respectively. Over 8wks, the number of ulcerations observed endoscopically decreased in 7/13 (54%) subjects, and the RHI improved in 9/13 (69%) subjects. Decreases in FCP were observed as early as wk2 in the subgroup achieving clinical remission (N=6), with a reduction of 68%, 71%, and 80% in median FCP at wk2, wk4, and wk8, respectively (Table 1).

Table 1. Changes (n, mean or median, IQR) in clinical, endoscopic, histologic, and biochemical disease activity observed upon treatment with MH002 in subjects achieving vs. not achieving mPDAI remission at wk8.

	Full Analysis Set (N=13)			mPDAI remission (N=6)			No mPDAI remission (N=7)
∆mPDAI, mean	13	-2.02	(-4.30; -0.30)	6	-4.10	(-4.68; -3.85)	7	-0.24	(-0.70; 0.15)
∆Clinical PDAI, mean	13	-1.10	(-1.70; -0.30)	6	-1.60	(-1.93; -0.85)	7	-0.67	(-1.20; -0.15)
∆Endoscopic PDAI, mean	13	-0.9	(-2.0; 0.0)	6	-2.5	(-3.0; -2.0)	7	0.4	(0.0; 1.0)
∆Histologic PDAI, mean	13	-0.5	(0.0; 0.0)	6	-1.0	(-2.3; 0.0)	7	-0.1	(0.0; 0.0)
∆Severity of urgency, mean	13	-1.31	(-2.00; 0.00)	6	-1.72	(-2.65; -0.25)	7	-0.96	(-1.70; 0.00)
FCP at baseline (mg/kg), median	13	391.0	(187.0; 864.0)	6	439.0	(218.5; 606.3)	7	391.0	(194.0; 1337.0)
FCP at wk2 (mg/kg), median	12	392.0	(124.0; 1407.5)	5	142.0	(32.0; 231.0)	7	653.0	(348.5; 1407.5)
FCP at wk4 (mg/kg), median	12	251.0	(45.5; 884.0)	6	129.0	(19.3; 259.0)	6	884.0	(310.3; 1140.5)
FCP at wk8 (mg/kg), median	12	354.5	(111.0; 483.5)	5	89.0	(22.0; 479.0)	7	355.0	(327.0; 429.0)

Conclusion

In this exploratory study in patients with acute pouchitis, 8-wk treatment with MH002 resulted in consistent and clinically meaningful improvements with a remission rate of 46% according to the mPDAI. These results warrant further development of MH002 in a phase 2/3 study.

Disclosure

SV: financial support for research from AbbVie, J&J, Pfizer, Takeda and Galapagos; speakers’ and/or consultancy fees from AbbVie, Abivax, AbolerISPharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MRM Health, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Surrozen, Takeda, Theravance, Tillots Pharma AG, VectivBio, Ventyx, Zealand Pharma.
PD: research support for from Biogen and Mundipharma; speakers’ fees from Biogen, Janssen, Dentsply and Dr Falk Pharma; congress support from Roche, Amgen, Ferring, Onis and Norgine; advisory board fees from Janssen, Sandoz, Samsung Bioepis, Galapagos and BMS.
TL: financial support for research from Abbvie, Ferring, Viatris, MSD, EG, Mundipharma, Biogen, Janssen, Pfizer, Takeda, Sandoz and Galapagos; speakers’ fees from MSD, Abbvie, Janssen, Amgen, Fresenius Kabi, Galapagos, Viatris, Ferring and Takeda; consultancy fees from Janssen, Galapagos, Amgen, Bristol Myers Squibb Fresenius Kabi, Takeda and Abbvie.
MA: consulting fees from Nikkiso Europe, Mundipharma, Janssen, Abbvie, Ferring, Galapagos and Pfizer.
FS: consulting fees from Janssen, Abbvie, Takeda, Celltrion, Ferring, Galapagos, Alfa Sigma, Sandoz and Pfizer.
SP, LH & SB: employee, paid consultant and/or shareholder of MRM Health.

Event

UEG Week Vienna 2024

Topics

IBD Mechanisms & Personalised Medicine

Submission format

Abstract

Session

IBD: New horizons in medical treatment - Part 1

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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