MaaT Pharma's MaaT013, a Microbiome Ecosystem Therapy, has demonstrated positive topline results in the pivotal Phase 3 ARES trial for patients with gastrointestinal acute graft-versus-host disease (GI-aGvHD). The study, conducted across 50 European sites, evaluated MaaT013 as a third-line treatment for GI-aGvHD in patients refractory to steroids and ruxolitinib. The results indicate a potential new option for patients with limited treatment alternatives.
The ARES trial met its primary endpoint, showing a significant gastrointestinal overall response rate (GI-ORR) of 62% at day 28, surpassing the expected 38% response rate (p < 0.0001). The study included 66 adult patients with GI-aGvHD who had not responded to previous treatments. The findings suggest that MaaT013 could address a critical unmet need in patients with alarmingly low survival rates.
Key Findings from the ARES Trial
The ARES trial revealed that patients treated with MaaT013 achieved a GI-ORR of 62%, with a complete response (CR) rate of 38% and a very good partial response (VGPR) rate of 20%. The overall response rate (ORR) in all evaluable organs was 64%, including a CR rate of 36% and a VGPR rate of 18%. These responses, assessed by an Independent Review Committee (IRC), exceeded the pre-specified response threshold.
Furthermore, the estimated 12-month overall survival (OS) rate was 54%. Among patients who responded to MaaT013 at day 28, the 12-month OS rate was 67%, compared to 28% for non-responders (P < .0001). This significant difference highlights the potential survival benefit of MaaT013 in this patient population.
Study Design and Patient Population
The ARES trial was a single-arm, open-label, multicenter study conducted in several European countries. The study enrolled adult patients with GI-aGVHD who had undergone allogeneic hematopoietic stem cell transplantation. Patients were required to be resistant to steroids and either resistant or intolerant to ruxolitinib.
Patients received pretreatment with oral vancomycin, followed by MaaT013 administered via rectal enema. The treatment regimen included multiple doses of MaaT013 over a three-week period, with a supplementary dose allowed in cases of GVHD relapse or significant antibiotic use.
The median age of the patients was 55.5 years, with a majority being male (53%). Most patients had grade III (57.6%) or grade IV (33.3%) aGVHD. All patients were refractory to ruxolitinib, and 86.4% were steroid refractory.
Safety and Tolerability
Previous safety data from the ARES trial indicated that MaaT013 was well-tolerated and not associated with increased infection risk or treatment-related fatal adverse effects. These findings were based on an interim safety analysis of the first 30 patients treated.
Regulatory Plans and Future Directions
MaaT Pharma is planning to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in mid-2025, seeking approval for MaaT013 as a third-line treatment for GI-aGVHD. The company is also expanding its Early Access Program (EAP) to the United States and preparing for a U.S. Phase 3 clinical trial, contingent on securing financing.
"These positive topline results strongly position MaaT013 as a first-in-class therapeutic for GI-aGVHD, potentially bringing a new option for patients in need of effective treatments when both steroids and ruxolitinib have failed," said Gianfranco Pittari, MD, PhD, chief medical officer of MaaT Pharma.
