Mesoblast isn’t giving up on its allogeneic cell therapy remestemcel-L. In September 2020, the FDA took the unusual step of going against its independent expert reviewers and knocked back the company's approval request for its mesenchymal stromal cell therapy in children with steroid-resistant graft-versus-host disease.
Now, the Australian cell therapy biotech has announced the submission of “substantial new information” regarding the clinical and potency assay issues raised in the FDA’s complete response letter two years ago. Mesoblast said it has been maintaining a dialogue with the agency since and branded the latest information it is providing as a “major milestone” in its response. However, the company was light on details of the information it had shared.
Mesoblast also met with the FDA in December 2021 regarding its approval request. At the time, the company said it had generated “substantial new data” to show that immunomodulatory activity is a suitable measure to show the therapy's clinical effect in response to one of the FDA's red flags regarding Mesoblast's use of inflammatory biomarkers.
Evidence of the agency's concerns with Mesoblast’s remestemcel-L filing first emerged in August 2020 when it released the briefing document that informs the discussion of the application by the Oncologic Drugs Advisory Committee (ODAC). The FDA cited multiple perceived shortcomings of the filing, including arguing that the ability of the therapy “to reduce inflammation as measured by inflammatory biomarkers in humans receiving the product has not been demonstrated.”
Despite the FDA’s concerns, ODAC members voted nine to one that the data support remestemcel-L's efficacy. However, the FDA made the rare call to go against the committee's recommendation. Instead, it asked Mesoblast to run at least one additional trial in adults or children with steroid-resistant graft-versus-host disease before refiling for approval.
Regarding the latest details provided to the FDA, Mesoblast CEO Silviu Itescu said in a release Sunday: “The submission summarizes controlled data, providing further evidence of remestemcel-L’s ability to save lives.
“Additionally, the improved process controls we have put in place to assure robust and consistent commercial product, together with a potency assay that predicts consistent survival outcomes, makes remestemcel-L a compelling treatment for these children.”
Mesoblast hasn’t had any more luck getting remestemcel-L approved for COVID-19 patients with acute respiratory distress syndrome (ARDS), either. The biotech was exploring this indication in collaboration with Novartis, but a year after it delivered the knock-back for graft-versus-host disease, the FDA requested an additional ARDS trial.
The U.S. agency's COVID decision marked another blow for Mesoblast, which lost out on potentially $1 billion in biobucks once Novartis exited the deal. Updated data for the drug in ARDS, published in May 2022, suggest remestemcel-L increased survival rates in patients less than 65 years old but not in older patients.