ARES Trial of MaaT013 in Acute GVHD Meets Primary End Point

Red blood cells flowing realistically, 3D rendering: © Kodjovi - stock.adobe.com

The primary end point of gastrointestinal (GI)-overall response rate (ORR) at day 28 has been met in the ARES study (NCT04769895), a phase 3 trial assessing MaaT013 in the third-line setting following treatment refractoriness to steroids or ruxolitinib (Jakafi) in patients with acute graft-versus-host disease (aGVHD) with GI involvement.¹

The ARES study was a single-arm trial conducted across 50 sites in Austria, Belgium, France, Germany, Italy, and Spain, focusing on 66 adult patients with GI-aGVHD refractory to steroids and refractory or intolerant to ruxolitinib. Patients received MaaT013, a donor-derived, standardized, high-richness, high-diversity microbiome ecosystem therapy, in the third-line setting.

Among the 66 patients, the GI-ORR was 62%, which included a complete response (CR) rate of 38% and a very good partial response (VGPR) rate of 20%. In all evaluable organs, the ORR was 64%, including a CR rate of 36% and a VGPR rate of 18%, respectively. The high GI-ORR at day 28 exceeded the expected response rate of 38%.

“GI involvement in aGVHD is a devastating condition, particularly for patients who do not respond to ruxolitinib,” said Mohamad Mohty, MD, PhD, a professor of hematology and head of the Clinical Hematology and Cellular Therapy Department at Saint-Antoine Hospital and Sorbonne University in Paris, France, in a press release. “These individuals face an urgent unmet medical need with alarmingly low survival rates and a critical lack of effective treatment options. The results for MaaT013 in this phase 3 trial represent a groundbreaking advancement in third-line treatment for GI-aGVHD. By directly targeting the gut-immune interface, this innovative therapy has the potential to redefine disease management, bringing new hope to patients and clinicians alike.”

For survival, the estimated 12-month overall survival (OS) rate was 54%, and the median OS was not yet reached. The estimated 12-month OS rate at day 28 was 67% among patients who responded vs 28% among those who did not respond (P < .0001).

“We would like to thank all patients who participated in this landmark study,” added Gianfranco Pittari, MD, PhD, chief medical officer of MaaT Pharma, in the press release. “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. ARES represents the first-ever positive pivotal clinical study for an immunosuppressant-sparing, microbiome-based approach, confirming MaaT Pharma’s leadership in the field, validating the company’s therapeutic platform, supporting its programs, and broadening potential applications in oncology, inflammation, and other therapeutic areas.”

About the ARES Study

Enrollment in the single-arm, phase 3 ARES study was open to patients undergoing allogeneic hematopoietic stem cell transplantation, regardless of donor type, stem cell source, GVHD prophylaxis strategy, or conditioning regimen.² Patients were required to have an episode of aGVHD with gastrointestinal involvement, as defined by the Mount Sinai Acute GVHD International Consortium guidelines, with or without additional organ involvement. Eligibility criteria also included steroid-refractory disease and resistance or intolerance to ruxolitinib or a contraindication to its use.

If eligible, patients received pretreatment with oral vancomycin (Vancocin) at a dose of 250 mg 4 times daily on days 0 and 1. On day 2, treatment began with a single dose of MaaT013 administered via rectal enema. Between days 3 and 5, patients received an additional dose of MaaT013, followed by another dose administered 7 ± 2 days after the prior dose during week 2, and a subsequent dose 7 ± 2 days after the prior dose during week 3. An optional supplementary dose of MaaT013 was allowed in cases of GVHD relapse or significant antibiotic use.

In addition to the primary end point of GI-ORR at day 28, secondary end points of the trial consisted of aGVHD ORR and GI-aGVHD ORR at various time points, best response rates, survival rates, duration of response, safety and tolerability, and chronic GVHD incidence and severity.

Of those enrolled and included in the data update, the median age was 55.5 years (range, 24.0-76.0).¹ The majority of patients were male (53%), all patients were refractory to ruxolitinib, and 86.4% of patients were steroid refractory. No patients were intolerant to ruxolitinib, 13.6% of patients were steroid dependent, and patients had grade II (9.1%), grade III (57.6%), or grade IV (33.3%) aGVHD.

Previously in October 2023, safety data from the first 30 patients in the ARES trial were reported, showing that MaaT013 was well tolerated and did not increase infection risk or treatment-related fatal adverse events. Pharmacovigilance and Data Safety Monitoring Board surveillance for the study remain ongoing.

With strong efficacy and safety data, the regulatory submission of MaaT013 is advancing in Europe as a third-line treatment for GI-aGVHD. The company plans to submit a Centralized Marketing Authorization Application to the European Medicines Agency by mid-2025, ahead of initial projections.

REFERENCES:

1. MaaT Pharma announces positive topline results from the pivotal phase 3 ARES study evaluating MaaT013 in acute graft-versus-host disease. News release. MaaT Pharma. January 8, 2025. Accessed January 10, 2025. https://tinyurl.com/w5uszczt

2. MaaT013 as salvage therapy in ruxolitinib refractory GI-aGVHD patients (ARES). ClinicalTrials.gov. Updated October 17, 2024. Accessed January 10, 2025. https://clinicaltrials.gov/study/NCT04769895