Microbiota Therapy MaaT013 Achieves 62% Response Rate in Refractory GI-aGVHD Phase 3 Trial
核心洞察
The phase 3 ARES trial demonstrated that MaaT013 achieved a 62% gastrointestinal overall response rate at day 28 in patients with refractory acute graft-versus-host disease, significantly exceeding the 22% historical control threshold.
Responses were durable with an average duration of 6.4 months, and responders showed a clear survival advantage over non-responders at one year follow-up.
The microbiota-based therapy showed an acceptable safety profile with treatment-related adverse events occurring in 29% of patients, primarily bacterial infections and gastrointestinal disorders.
The microbiota-based therapeutic MaaT013 demonstrated significant efficacy in treating patients with refractory acute graft-versus-host disease (aGVHD) with gastrointestinal involvement, according to primary analysis data from the phase 3 ARES trial presented at the 67th American Society of Hematology Annual Meeting and Exposition.
The single-arm, multicenter, open-label European trial enrolled 66 adult patients who had undergone allogeneic hematopoietic stem cell transplantation and subsequently developed refractory aGVHD with lower gastrointestinal symptoms. All patients were resistant to systemic steroids and either resistant or intolerant to ruxolitinib.
Primary Efficacy Results
The study met its primary endpoint with a gastrointestinal overall response rate (GI-ORR) of 62% (95% CI, 49%-74%) at day 28, significantly exceeding the pre-established historical control threshold of 22% (P <0.0001). Among responders, 38% achieved a complete response, 20% achieved a very good partial response, and 5% achieved a partial response.
The all-organ overall response rate was 64% (95% CI, 51%-75%) at day 28. Notably, both gastrointestinal and all-organ responses exhibited similar durability with an average duration of response of 6.4 months (95% CI, 4.8-8.0).
Sustained Response and Survival Benefits
Response rates remained substantial at later timepoints, with GI-ORRs of 49% at day 56 and 44% at month 3. All-organ ORRs were 48% at day 56 and 44% at month 3. Responses across all time points showed exceptionally high rates of complete response and very good partial response.
The deep and durable responses translated into promising survival benefits. Kaplan-Meier analysis showed separation of survival curves between responders and non-responders beginning shortly after the first administration of MaaT013, with the gap widening substantially over one year. While median overall survival data were immature at the time of analysis, the estimated probability of survival at one year was 54%, representing a clinically meaningful improvement for this patient population with historically poor outcomes.
Safety Profile
MaaT013 demonstrated an acceptable safety profile. There were 157 serious treatment-emergent adverse events reported across 76% of patients, with the most common being escherichia sepsis, general physical health deterioration, and septic shock.
Treatment-related adverse events occurred in 29% of patients (34 total events), primarily comprising bacterial infections and gastrointestinal disorders. Seven of these events were considered serious. There were 26 fatal adverse events, with one case of septic shock determined to be related to MaaT013 by investigators.
Treatment Protocol and Patient Population
Enrolled patients underwent a two-day course of oral vancomycin followed by rectal administration of three MaaT013 doses delivered as a 150-mL enema. Patients experiencing relapse after day 28 could receive a single supplementary dose.
The majority of patients (77%) had aGVHD with involvement limited to the gastrointestinal tract, while others had gastrointestinal and skin involvement (17%), gastrointestinal and liver involvement (3%), and involvement of all three organs (3%).
Regulatory Status and Future Implications
MaaT013 is currently under regulatory review by the European Medicines Agency following submission of a marketing authorization application in June 2025, with a decision regarding approval anticipated in the second half of 2026. If approved, MaaT013 would become the first microbiome-based therapy for the treatment of refractory GI-aGVHD.
According to lead investigator Florent Malard of Sorbonne Université (搜索), preliminary data from the previous phase 2 HERACLES study suggested the therapy works through systemic immunomodulatory effects, including decreased proinflammatory cytokines and increased essential fatty acids in patient serum. Further studies are planned to evaluate immune cell subsets, particularly regulatory T cells, to better understand the mechanism of action.