FDA lifts 18-month clinical hold on MaaT Pharma’s microbiome therapeutic

By Jonathan Smith

- Last updated on GMT


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More than a year after imposing a clinical hold on MaaT Pharma’s lead microbiome therapeutic in 2021, the US Food and Drug Administration (FDA) has given clearance for the French firm to begin a phase 3 trial in the US.

MaaT Pharma is developing its lead candidate MaaT013 for the treatment of graft-versus-host disease (GvHD). GvHD is a serious complication that can occur when patients with blood cancer receive a bone marrow transplant, and the grafted immune cells attack the patient’s healthy tissues. The condition is also linked to disruptions in the gut microbiome caused by the use of antibiotics and chemotherapy.

MaaT013 consists of a consortium of microbiota derived from the stool from healthy donors. MaaT Pharma pools and processes donated stool samples to improve their richness and diversity, with a focus on bacteria that produce anti-inflammatory molecules. MaaT013, delivered via an enema, is designed to restore the microbiome to a healthy state and calm the immune cells driving GvHD.

Following promising phase 2 data in Europe, MaaT Pharma launched a phase 3 trial of MaaT013 as a third line treatment for patients with acute GvHD with gastrointestinal involvement. The trial, dubbed ARES​, specifically enrols patients in European trial sites who don’t respond to current GvHD treatments including steroids and ruxolitinib.

Talks with the FDA

In contrast to its progress in Europe, MaaT Pharma had a harder time in the US. The company initially submitted an Investigational New Drug (IND) application to the FDA in mid-2021, asking for clearance to launch a phase 3 trial of MaaT013. In August 2021, however, the FDA raised questions regarding the therapeutic and placed a clinical hold on the testing of MaaT013 in the US.

MaaT Pharma sent off answers to the FDA’s questions, however, in August 2022, MaaT Pharma announced that the FDA was maintaining the clinical hold. The agency was satisfied with MaaT Pharma’s responses to its earlier questions, however, it made suggestions for the phase 3 trial design and asked for extra information related to the safety and efficacy of MaaT’s strategy of pooling stool samples.

MaaT Pharma sent off detailed responses to the FDA in January 2023 and one month later announced that the agency agreed to adding conditions in the IND application that allow the clinical testing of MaaT013. This opened the way to the recent lifting of the clinical hold, and to the development of MaaT013 in the U.S.

“This is the first time the [FDA] has authorized the phase 3 clinical evaluation in the U.S of a microbiota-based live biotherapeutic based on a pooling technology, which provides greater bacterial diversity, in a standardized and scalable approach, with the goal of safely improving patients’ outcomes. This major milestone is fundamental to the strategic decisions regarding the development of our portfolio outside Europe and to the Company’s outlook in the U.S.,” stated Hervé Affagard, CEO and co-founder of MaaT Pharma.

“The US represents an important market for our therapeutics, and we have already benefited from our previous discussions with the FDA by adapting our pooling technology for our entire pipeline according to the guidelines received during this regulatory process.” 

Parallel development

As MaaT Pharma clears its U.S. hurdles, the company is continuing its development of MaaT013 in the European ARES trial, whose scheduled primary completion date is September 2023. Additionally, the Assistance Publique–Hôpitaux de Paris (AP-HP) is leading a phase 2a trial of MaaT013 combined with immune checkpoint inhibitors for the treatment of metastatic melanoma.

MaaT’s second microbiome therapeutic, MaaT033, is also in development to improve survival in patients that receive allogeneic bone marrow transplants, who can suffer from severe complications including severe infections, graft-vs-host-disease and neutropenia. The candidate produced positive phase 1b results in 2022, and MaaT Pharma is launching a phase 2b trial in Europe, while discussing the potential for clinical trials of MaaT033 in the US.

MaaT Pharma also has its eye on using MaaT033 to tackle the neurodegenerative disease amyotrophic lateral sclerosis, which has been linked to imbalances in the gut microbiome. To test the potential of the therapeutic in ALS, MaaT Pharma is preparing a phase 1b pilot study, with the first patient expected to be included in early 2023.

Emerging microbiome therapies

Microbiome therapeutics are still in their infancy, with only one approved by the U.S. FDA so far: Ferring Pharmaceuticals’ Rebyota. Rebyota was greenlit in November 2022 for the treatment of recurrent Clostridioides difficile infections in patients that have already received antibiotics.

Nonetheless, MaaT Pharma isn’t the only company grappling with obstacles in the microbiome field. In January 2023, Finch Therapeutics announced plans to lay off 95% of its workforce and shelve a phase 3 trial in recurrent C. difficile infections. Factors behind this move included difficulty in obtaining financing or partnerships, as well as the impact of safety concerns from donor stool samples.

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