DSMB Confirms MaaT013 Efficacy/Benefit in GI-aGvHD

Evaluation of the 1-year overall survival data in the phase 3 ARES trial assessing MaaT013 in GVHD is expected to occur Q4 2025.

The Independent Data Safety and Monitoring Board (DSMB) confirmed improved efficacy results and positive benefit/risk profile of MaaT013, a microbiome ecosystem therapy, as a third-line option for patients with acute graft-versus-host disease with gastrointestinal involvement (GI-aGvHD) refractory to steroids and refractory or intolerant to ruxolitinib (Jakafi), according to a press release from the drug’s developer, MaaT Pharma.¹

This confirmation followed a recent approval from the Pediatric Investigation Plan (PIP) for MaaT013 by the EMA Pediatric Committee.²

Support from the decision follows efficacy findings from the phase 3 ARES study (NCT04769895), which evaluated the therapy as a third-line treatment for GI-aGvHD. The trial met its primary end point of a significant GI overall response rate (GI-ORR) at 28 days of 62% as assessed by an independent review committee (IRC), exceeding the expected 38% GI-ORR (P <.0001).³ Additionally, 38% of the study cohort reached a complete response (CR), and 20% experienced a very good partial response (VGPR).

ORR in all evaluable organs occurred in 42 (64%) patients, with similarly high CR (36%) and VGPR (18%) rates. Furthermore, the estimated 12-month overall survival (OS) rate was 54% for this patient population, with a median OS not yet reached. Additionally, the 12-month estimated rate at day 28 among responders was 67% vs 28% among non-responders (P <.0001).

“This DSMB’s positive review is another key milestone for MaaT Pharma, further validating MaaT013’s consistently favorable clinical profile, demonstrated over the years in clinical development in a highly fragile patient population,” Gianfranco Pittari, MD, PhD, chief medical officer of MaaT Pharma, remarked in the news release.¹ “It underscores our determination to enhance outcomes in patients with aGvHD through innovative therapies.”

Patients enrolled were pretreated with 250 mg of oral vancomycin 4 times daily on days 0 and 1 of the study period and received the first dose through an enema of MaaT013 on the second day.⁴

Patients received the second dose of MaaT013 of up to 4 enemas between days 3 and 5 of the study period. Subsequent doses were administered between days 5 and 9 after the previous dose, with a supplementary dose allowed in the event of GvHD relapse or massive antibiotic use during the study period.

Patients in the study were majority males (53%), had a median age of 55.5 years (range, 24-76), and were stage I or II (9.1%), III (57.6%), or IV (33.3%) aGVHD at baseline according to both IRC and investigator assessments. Additionally, 86.4% of patients were steroid-refractory and all were refractory to ruxolitinib (Jakafi).

The primary end point of the study was GI-ORR at 28 days. Secondary end points included the safety and tolerability of MaaT013, aGvHD ORR, best response rates for both GI-aGvHD and aGvHD in all evaluable tumors, progression-free survival, OS, and duration of response.

The DSMB, which comprised 4 independent experts, concluded that MaaT013 demonstrated a positive benefit/risk ratio based on the safety profile and positive preliminary efficacy results of the ARES trial after previously reviewing data on 30 patients in October 2023.⁵ They completed their review from 66 patients up to the data cut-off of the primary analysis at the last meeting. They will continue to review safety on an ongoing basis up to the 1-year follow-up.

The submission of a centralized marketing authorization application (MAA) to the EMA is anticipated for June 2025. Additionally, a secondary end point evaluation of 1-year OS is expected to occur in Q4 2025.

References

1. MaaT Pharma announces positive outcomes from final DSMB meeting for pivotal phase 3 clinical trial evaluating MaaT013 in acute graft-versus-host disease. News release. MaaT Pharma. March 18, 2025. Accessed March 20, 2025. https://tinyurl.com/39f7j52m
2. MaaT Pharma receives positive opinion from EMA Pediatric Committee on the Pediatric Investigation Plan for MaaT013. News release. MaaT Pharma. March 11, 2025. Accessed March 20, 2025. https://tinyurl.com/yfa4vr28
3. 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 March 20, 2025. https://tinyurl.com/ymc23ny4
4. MaaT013 as salvage therapy in ruxolitinib refractory GI-aGVHD Patients (ARES). ClinicalTrials.gov. Updated October 17, 2024. Accessed March 20, 2025. https://tinyurl.com/55afnkhy
5. MaaT Pharma announces positive outcome following DSMB review reinforcing confidence in phase 3 on-going trial in acute graft-versus-host disease with MaaT013. October 26, 2023. Accessed March 20, 2025. https://tinyurl.com/mpvyjwvj