FDA wants more answers before releasing clinical hold on MaaT’s GvHD drug

FDA wants more answers before releasing clinical hold on MaaT’s GvHD drug

Published: Aug 11, 2022

By Tristan Manalac

BioSpace

French biotech MaaT Pharma announced Wednesday that the U.S. Food and Drug Administration has maintained the clinical hold on MaaT013, its candidate for patients with steroid-resistant acute graft-versus-host disease  (aGvHD).

MaaT first submitted an investigational new drug (IND) application for MaaT013 back in June 2021, seeking to start a Phase III, open-label, single-arm study of its candidate in the U.S. In August the same year, the federal agency replied with a clinical hold letter, along with questions about safety and efficacy. 

The clinical-stage company has since sent over detailed answers to these questions and a request for a type A meeting, which is intended to help companies with their stalled product. MaaT CEO and Co-founder Hervé Affagard attests that data from over 120 MaaT013-treated patients from an early access program in France and a completed Phase II trial in Europe show that the candidate is safe and effective for aGvHD.

The FDA acknowledges that MaaT’s responses to several of its clinical and manufacturing-related concerns were satisfactory but has decided to maintain the clinical hold while it requests more information about how MaaT013 was developed. The regulatory body has also provided MaaT with a list of recommendations regarding trial design.

“We value the FDA’s continued engagement as we seek to extend the Phase 3 clinical trial of MaaT013 to the U.S. and we intend to work with the Agency to resolve the issues raised in the communication while implementing a defined strategic plan to continue to deliver on our key milestones,” Affagard said in a statement.

In particular, the FDA has raised concerns about the safety and efficacy of MaaT’s pooling approach to their candidate’s formulation. 

MaaT013 treats aGvHD by restoring the symbiosis between a patient’s immune system and the gut microbiome. The candidate is a full-ecosystem, off-the-shelf biotherapeutic enema that was developed by mixing samples from several donors. While the FDA has flagged this pooling approach, MaaT maintains that this is how their candidate achieves a high level of species diversity and richness while also making the end product better standardized for broader use.

In response to the clinical hold, MaaT is engaging with the FDA in hopes of setting up a type A meeting to discuss these issues more thoroughly. “We remain focused on bringing innovative and safe microbiome therapies to patients with refractory aGvHD,” Affagard said.

In the meantime, MaaT013 will continue clinical assessments in Europe. The candidate returned promising results in the Phase II HERACLES trial in March last year. Topline data showed that it could elicit a 33% combined complete and very good partial response rate in 21 heavily pre-treated, immunocompromised patients. 

Follow-up data, presented in November of the same year, confirmed that in patients who had failed a median of three prior lines of systemic therapy, MaaT013 was able to elicit a good objective gastro-intestinal response rate without inducing alarming safety signals. Earlier this year, MaaT was able to initiate a pivotal Phase III study for its candidate, dosing its first patient in March. This trial is set to enroll 75 patients across 19 clinical sites in France, Germany and Spain.

Source: BioSpace