Remedy with Zervyteg (MaaT013) generated encouraging outcomes and demonstrated an appropriate security profile in sufferers with acute graft-vs-host illness that impacts the gastrointestinal tract and doesn’t reply to corticosteroids or Jakafi (ruxolitinib), in response to major findings from the ARES trial.
Information from the part 3 examine had been introduced by Dr. Florent Malard on the 67th American Society of Hematology (ASH) Annual Assembly and Exposition in Orlando, Florida.
As of the information cutoff on November 11, 2024, the examine met its major finish level with a GI general response charge of 62% amongst 66 sufferers handled with Zervyteg on day 28 of therapy, considerably exceeding the historic management of twenty-two%. The all-organ general response charge was 64%. Notably, each GI and all-organ responses exhibited the same common period of response of 6 months.
Moreover, information describing key secondary finish factors revealed that responses had been maintained by means of later time factors. At day 56 and month 3, the GI general response charges had been 49% and 44% respectively; likewise the all-organ general response charges had been 48% and 44% respectively. Responses throughout all time factors confirmed exceptionally excessive charges of full response and superb partial response.
Importantly, the deep and sturdy responses translated into survival advantages. A Kaplan-Meier graph displayed a separation of curves between responders and non-responders starting shortly after the primary administration of Zervyteg, widening considerably over the course of 1 12 months with responders sustaining a transparent survival benefit over time. Median general survival information had been immature on the time of research, however the estimated likelihood of survival at 1 12 months was 54%, a clinically significant enchancment for this affected person inhabitants with traditionally poor scientific outcomes.
Understanding the Security and Tolerability of Zervyteg
Zervyteg’s security profile was decided to be acceptable. There have been 157 severe treatment-emergent unwanted effects reported throughout 76% of sufferers, with the commonest being escherichia sepsis, basic bodily well being deterioration, and septic shock.
There was a complete of 34 treatment-related unwanted effects throughout 29% of sufferers, which primarily comprised varied bacterial infections and GI issues. Of those occasions, 7 had been thought of severe. There have been 26 deadly unwanted effects, with 1 occasion of septic shock decided to be associated to Zervyteg by investigators.
Extra Data on the Use of Zervyteg and the ARES Trial
The part 3 ARES trial is a single-arm multicenter open-label trial in Europe investigating Zervyteg, a pooled allogeneic fecal microbiotherapy, as salvage remedy in grownup sufferers with refractory GI acute graft-versus-host illness (GVHD). The first finish level of the trial is GI general response charge at day 28 assessed by an unbiased evaluation committee; secondary finish factors embrace GI general response charge at day 56 and month 3, all-organ general response charge at day 28, and period of response per unbiased evaluation committee and investigator evaluation, in addition to general survival. Within the examine, Zervyteg was administered as a rectal suspension as a 150 mL enema.
Sufferers had been included if that they had undergone allogeneic hematopoietic stem cell transplant, skilled an acute GVHD episode with decrease GI signs per MAGIC tips, and had been proof against systemic steroids and both resistant or illiberal to Jakafi. Key exclusion standards included having lively cytomegalovirus colitis, strains of acute GVHD therapy aside from steroids and Jakafi, hyperacute GVHD, and lively uncontrolled an infection.
Of the 66 complete sufferers, the bulk (77%) had acute GVHD with involvement restricted to the GI tract. Others had GI and pores and skin involvement (17%), GI and liver involvement (3%), and involvement of all 3 organs (3%). Concerning the hypothesized mechanisms of motion driving responses within the pores and skin and liver, Malard supplied preliminary insights based mostly on earlier analysis.
“Up to now, based mostly on this examine, we don’t have the translational information to analyze how that is working, however from the earlier 2 HERACLES examine we have already got some information on the truth that we have now some systemic immunomodulatory impact of the drug with some lower within the proinflammatory cytokine on the systemic degree and in addition a rise in important fatty acid… within the serum of the affected person,” Malard defined within the question-and-answer session. “We’re additionally going to guage in one other examine all of the immune cell subsets, specifically Tregs and so forth, to seek out if that is the way it’s working.”
Zervyteg is at present beneath regulatory evaluation by the EMA following submission of a advertising and marketing authorization utility in June 2025, with a call concerning approval anticipated within the second half of 2026. If authorized, Zervyteg would develop into the primary microbiome-based remedy for the therapy of this high-need illness.
References
- “MaaT013 for ruxolitinib-refractory acute graft-versus-host illness with gastrointestinal involvement: Outcomes from the ARES part III trial,” by Dr. Florent Malard. Blood.
- “MaaT013 as salvage remedy in ruxolitinib-refractory GI-aGVHD sufferers (ARES),” by ClinicalTrials.gov. Up to date October 17, 2024. https://clinicaltrials.gov/examine/NCT04769895
- “Maat Pharma pronounces optimistic part 3 outcomes evaluating Xervyteg® (MaaT013) in acute graft-versus-host illness chosen for oral presentation at ASH Congress 2025,” by MaaT Pharma. Information launch; Nov. 3, 2025.
For extra information on most cancers updates, analysis and schooling, don’t neglect to
