Zervyteg Shows Strong Responses in Acute Graft-Versus-Host Disease

Treatment with Zervyteg (MaaT013) generated encouraging results and demonstrated an acceptable safety profile in patients with acute graft-vs-host disease that affects the gastrointestinal tract and does not respond to corticosteroids or Jakafi (ruxolitinib), according to primary findings from the ARES trial.

Data from the phase 3 study were presented by Dr. Florent Malard at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.

As of the data cutoff on November 11, 2024, the study met its primary end point with a GI overall response rate of 62% among 66 patients treated with Zervyteg on day 28 of treatment, significantly exceeding the historical control of 22%. The all-organ overall response rate was 64%. Notably, both GI and all-organ responses exhibited a similar average duration of response of 6 months.

Furthermore, data describing key secondary end points revealed that responses were maintained through later time points. At day 56 and month 3, the GI overall response rates were 49% and 44% respectively; likewise the all-organ overall response rates were 48% and 44% respectively. Responses across all time points showed exceptionally high rates of complete response and very good partial response.

Importantly, the deep and durable responses translated into survival benefits. A Kaplan-Meier graph displayed a separation of curves between responders and non-responders beginning shortly after the first administration of Zervyteg, widening substantially over the course of 1 year with responders maintaining a clear survival advantage over time. Median overall survival data were immature at the time of analysis, but the estimated probability of survival at 1 year was 54%, a clinically meaningful improvement for this patient population with historically poor clinical outcomes.

Understanding the Safety and Tolerability of Zervyteg

Zervyteg’s safety profile was determined to be acceptable. There were 157 serious treatment-emergent side effects reported across 76% of patients, with the most common being escherichia sepsis, general physical health deterioration, and septic shock.

There was a total of 34 treatment-related side effects across 29% of patients, which mainly comprised various bacterial infections and GI disorders. Of these events, 7 were considered serious. There were 26 fatal side effects, with 1 event of septic shock determined to be related to Zervyteg by investigators.

More Information on the Use of Zervyteg and the ARES Trial

The phase 3 ARES trial is a single-arm multicenter open-label trial in Europe investigating Zervyteg, a pooled allogeneic fecal microbiotherapy, as salvage therapy in adult patients with refractory GI acute graft-versus-host disease (GVHD). The primary end point of the trial is GI overall response rate at day 28 assessed by an independent review committee; secondary end points include GI overall response rate at day 56 and month 3, all-organ overall response rate at day 28, and duration of response per independent review committee and investigator assessment, as well as overall survival. In the study, Zervyteg was administered as a rectal suspension as a 150 mL enema.

Patients were included if they had undergone allogeneic hematopoietic stem cell transplant, experienced an acute GVHD episode with lower GI symptoms per MAGIC guidelines, and were resistant to systemic steroids and either resistant or intolerant to Jakafi. Key exclusion criteria included having active cytomegalovirus colitis, lines of acute GVHD treatment other than steroids and Jakafi, hyperacute GVHD, and active uncontrolled infection.

Of the 66 total patients, the majority (77%) had acute GVHD with involvement limited to the GI tract. Others had GI and skin involvement (17%), GI and liver involvement (3%), and involvement of all 3 organs (3%). Regarding the hypothesized mechanisms of action driving responses in the skin and liver, Malard offered preliminary insights based on earlier research.

“So far, based on this study, we don’t have the translational data to investigate how this is working, but from the previous 2 HERACLES study we already have some data on the fact that we have some systemic immunomodulatory effect of the drug with some decrease in the proinflammatory cytokine at the systemic level and also an increase in essential fatty acid… in the serum of the patient,” Malard explained in the question-and-answer session. “We are also going to evaluate in another study all the immune cell subsets, in particular Tregs and so on, to find if this is how it’s working.”

Zervyteg is currently under regulatory review by the EMA following submission of a marketing authorization application in June 2025, with a decision regarding approval anticipated in the second half of 2026. If approved, Zervyteg would become the first microbiome-based therapy for the treatment of this high-need disease.

References

1. “MaaT013 for ruxolitinib-refractory acute graft-versus-host disease with gastrointestinal involvement: Results from the ARES phase III trial,” by Dr. Florent Malard. Blood.‌
2. “MaaT013 as salvage therapy in ruxolitinib-refractory GI-aGVHD patients (ARES),” by ClinicalTrials.gov. Updated October 17, 2024. https://clinicaltrials.gov/study/NCT04769895
3. “Maat Pharma announces positive phase 3 results evaluating Xervyteg® (MaaT013) in acute graft-versus-host disease selected for oral presentation at ASH Congress 2025,” by MaaT Pharma. News release; Nov. 3, 2025.

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