MaaT013 in 2022 was put under clinical hold by the FDA, which cited safety and efficacy concerns with the sample-pooling method used to produce the investigational therapy. The hold was lifted in April 2023.
MaaT Pharma on Wednesday unveiled topline data from its Phase III ARES trial, demonstrating that its investigational graft-versus-host disease therapy MaaT013 can elicit high gastrointestinal response and a survival benefit in the third-line setting.
At 28 days, MaaT reported a gastrointestinal objective response rate (ORR) of 62%—easily exceeding the expected rate of 38%. Most responders achieved a complete response and a very good partial response, with respective rates of 38% and 20%. ORR across all evaluable organs was also high at 64%, an effect that was likewise driven heavily by complete and very good partial responses.
These strong treatment response outcomes translated into longer survival, according to MaaT, which touted a 54% probability of survival at 12 months. Survival estimates were significantly higher in patients who showed signs of response at 28 days than in those who did not respond—survival probabilities were 67% and 28% for these subgroups, respectively, with a p-value less than 0.0001 for their difference. Median survival had not yet been reached in ARES at the time of the readout.
“ARES represents the first-ever positive pivotal clinical study for an immunosuppressant-sparing, microbiome-based approach” to GVHD, MaaT chief medical officer Gianfranco Pittari said in a statement. “These positive topline results strongly position MaaT013 as a first-in-class therapeutic” for acute GVHD with gastrointestinal involvement (GI-aGvHD), he added.
With Wednesday’s promising late-stage findings, MaaT plans to plans to file a regulatory submission for MaaT013 in Europe by mid-2025, positioning the drug candidate as a third-line treatment for GI-aGvHD. The company did not disclose FDA plans in its news release.
MaaT013 is an off-the-shelf, full-ecosystem enema therapy that works by restoring harmony and balance between a patient’s immune system and gut microbiome. The investigational treatment was developed by mixing samples from several donors, giving it its high microbial diversity and richness, and contains Butycore, a proprietary group of bacteria with anti-inflammatory activity.
In March 2021, MaaT unveiled data from the Phase II HERACLES study, touting a 33% combined complete and very good partial response rate in acute GVHD patients who were immunocompromised and heavily pre-treated.
The following year, however, MaaT013’s development hit a roadblock when the FDA placed the experimental therapy under clinical hold, citing uncertainties surrounding its development. In particular, the regulator raised safety and efficacy concerns regarding the pooling of samples to produce MaaT013. The FDA lifted the clinical hold in April 2023 and gave the biotech the go-ahead to conduct a Phase III study of MaaT013 in the U.S.
