Ann: Update on BLA for Graft Versus Host Disease, page-677

FDA hits Mesoblast with CRL, asking for more adult data in acute graft-versus-host disease
Katherine Lewin
News Reporter
The FDA handed a complete response letter to Mesoblast for its BLA submission of its drug for pediatric steroid-refractory acute graft-versus-host disease (SR-aGVHD), the company announced Friday, adding another delay in a winding journey for remestemcel-L.
The agency wants more data in adult patients before it will approve the drug. Mesoblast said it’s planning on a controlled study in high-risk adults whose previous therapies haven’t worked and whose 90-day survival is as low as 20% to 30%. The adult study is in line with what it had planned to do in a sequential move from pediatric to adult SR-aGVHD, as adults make up 80% of the market for the disease, the company added in its statement.
“FDA’s inspection of our manufacturing process resulted in no observed concerns, the Agency raised no safety issues across more than 1300 patients who have received remestemcel-L to date, and acknowledged improvements to our potency assay,” Mesoblast CEO Silviu Itescu said in the statement.
Mesoblast will have a Type A meeting with the FDA within 45 days to agree on the new study’s trial design.
This is the second go-around for remestemcel-L after the FDA initially rejected the drug submission in 2020, objecting to Mesoblast’s single arm, open-label trial and asking for Mesoblast to improve its potency measurements for the stem cell therapy, expressing unease about the inconsistent batch-to-batch potency.
The FDA’s first rejection came even after the Oncologic Drugs Advisory Committee gave a thumbs-up by a 9-1 vote that year. The committee was not concerned about the trial design and didn’t see the need for an additional study at the time.
In October 2022, Mesoblast said that it had added new information on an optimized potency assay to the IND file on the drug, setting the biotech up to resubmit its BLA.
This spring, the FDA finally did accept Mesoblast’s resubmission, which had new long-term survival data from a Phase III trial, details on manufacturing changes undertaken during development, even more information about the biomarkers and other clinical information, and put remestemcel-L into a study comparing it against other drugs.
Mesoblast said the follow-up data from the pediatric Phase III trial showed 50% survival in more than four years of follow-up for patients who had less than 20% survival expectancy at two years. The company’s resubmission also showed six-month survival was 67% with remestemcel-L versus 10% with other unapproved therapies in the highest-risk patients.

https://endpts.com/fda-hits-mesoblast-with-crl-for-remestemcel-l-wants-adult-data-in-acute-gvhd/