Following a Type A meeting with the regulator, the biotech says it has clarity about the next steps in demonstrating remestemcel-L’s effectiveness in acute graft-versus-host disease.
Pictured: A yellow line pointing the way out of a maze/iStock, aprott
Following a Type A meeting with the FDA, Mesoblast claims it has a better understanding of what the regulator needs in order to consider approving remestemcel-L in the treatment of pediatric and adult steroid-refractory acute graft versus host disease, the company announced Thursday.
Mesoblast’s recent Type A meeting is the latest development in what has already been a long regulatory road for remestemcel-L. The company filed its first Biologics License Application in 2019 and even won strong support from the FDA’s Oncologic Drugs Advisory Committee in August 2020. Still, the regulator handed a surprise rejection in October 2020.
Mesoblast filed a resubmission, which the FDA accepted in March 2023—and subsequently denied last month.
In both rejections, the FDA pointed to the same issues that it raised during the Type A meeting: the potency assay and an adult-population study.
The FDA flagged the lack of a suitable potency assay for the candidate used during a Phase III trial in pediatric patients. According to the regulator, this has been a crucial roadblock in considering the trial an “adequate study” that could demonstrate remestemcel-L’s effectiveness.
To rectify this, Mesoblast plans to produce new potency assay data in the coming months, which should show that the product used in the Phase III study “was standardized as to its identity, strength, quality, purity, and dosage form,” according to the biotech’s press release. These new assay data should also prove that subsequent commercial batches for the pediatric indication will also meet the same standard, the company contends.
For remestemcel-L’s adult indication, Mesoblast has proposed an externally controlled single-arm registrational trial in patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD) who had failed prior treatment with both steroids and a second-line intervention.
This study will also be “underpinned by a suitable potency assay,” the company said in its Thursday announcement, adding that the additional assay data “will provide a link” between the remestemcel-L product used in the pediatric study and the one it plans to use in the adult trial.
However, Mesoblast has yet to align with the FDA regarding the design of its adult study, though it noted that the FDA was willing to consider its proposed protocol.
In a statement, CEO Silviu Itescu called the Type A meeting “very productive,” allowing the company to “establish the path forward for potential approval of remestemcel-L in SR-aGVHD.”
According to Mesoblast’s website, remestemcel-L is an investigational allogeneic cell therapy that uses culture-expanded mesenchymal stromal cells which, when administered, suppress pro-inflammatory cytokines and boosts the body’s anti-inflammatory response. This mechanism of action allows the candidate to dampen the immune response underlying aGVHD.
Remestemcel-L is still investigational in the U.S. but it has won regulatory approval in other territories, such as Canada and New Zealand, where it is marketed under the brand name Ryoncil.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
