In mid-August, the US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee voiced support for the efficacy of remestemcel-L in children with steroid-resistant graft-versus-host (GvHD) disease. The positive vote moved Mesoblast a step closer to winning approval for the mesenchymal stem cell therapy.
While seeking approval in that long-targeted indication, Mesoblast is also working to show the cell therapy is effective in patients with acute respiratory distress syndrome (ARDS) caused by infection with SARS-CoV-2.
Talking to investors on a fourth quarter results conference call late last week, Mesoblast CEO Silviu Itescu explained how the potential size of the COVID-19 market opportunity creates a “substantial challenge.”
“We ... have to be prepared to substantially scale up manufacturing ... to be in a position next year to make sufficient quantity of product to start to meet some of this unmet need. We are able to implement proprietary xeno-free technologies and we certainly have plans to move into 3D bioreactors to allow us to have sufficient capability to meet this large unmet need,” said Itescu.
Like many organizations targeting COVID-19, including groups such as AstraZeneca and Regeneron Pharmaceuticals that have large in-house operations, Mesoblast is planning to partner to gain the scale needed to manufacture the quantities of remestemcel-L it may need.
Mesoblast is currently running a phase 3 trial of remestemcel-L in ARDS. Itescu is assuming that the company will be entering into a “strategic partnership for manufacturing commercialization” to serve the ARDS indication.
The need for remestemcel-L in ARDS will depend on the progress of COVID-19 vaccines, which could significantly reduce the number of people suffering the complication of SARS-CoV-2 infection, and the strength of the phase 3 data.
Itescu explained the rationale for developing remestemcel-L in COVID-19 on the conference call. Like GvHD, a hyperactive immune response, known as a cytokine storm, is implicated in ARDS. In ARDS the cytokine storm manifests in severe inflammation of the lungs.
Remestemcel-L has shown anti-inflammatory effects during its development in GvHD. In addition, there is evidence the cell therapy migrates to the lungs after intravenous administration, suggesting it will accumulate in the part of the body where it is needed most in ARDS,
US physicians administered remestemcel-L to ventilator-dependent patients under a compassionate use program earlier this year. Nine of the 12 patients were taken off ventilator support, after 10 days in median, and later discharged from the hospital.
The evidence to support the use of remestemcel-L in COVID-19 led Mesoblast to start a 300-subject clinical trial. Mesoblast is assessing the effect of remestemcel-L on mortality after 30 days and is set to hold a series of interim analyses as increasing percentages of participants reach that point. If the data link remestemcel-L to improved survival, Mesoblast will seek expedited regulatory approval.