This is a developing story and will be updated with new information as it becomes available.
The FDA has approved Mesoblast’s allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy remestemcel-L for the treatment of steroid refractory acute graft versus host disease (GvHD) in children aged 2 months or older.1
Notably, the product is the first MSC therapy to have been approved by the FDA. It will be marketed under the name Ryoncil.
“Today’s decision marks an important milestone in the use of innovative cell-based therapies to treat life-threatening diseases with devastating impacts on patients, including children,” Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in a statement.1 “This first mesenchymal stromal cell therapy approval demonstrates the FDA’s commitment to supporting the development of safe and effective products that could improve the quality of life for patients with symptoms that are unresponsive to other therapies.”
The FDA's decision was made with regard to a biologics license application (BLA) that Mesoblast resubmitted on July 8, 2024, after 2 prior BLA submissions.2,3 In March 2024, the FDA had informed Mesoblast that the available data from the phase 3 MSB-GVHD001 clinical trial (NCT02336230), including new requested Chemistry, Manufacturing, and Control (CMC) information previously requested, were sufficient for a BLA resubmission. The new data provided further evidence from potency assays demonstrating a suitable link between product used for the pediatric indication to the adult indication.4
The FDA notes that 54 children were treated with remestemcel-L in the MSB-GVHD001 study after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).1 Among those treated, 16 patients (30%) had achieved a complete response 28 days after beginning treatment and 22 patients (41%) had achieved a partial response. A partial response was defined as an improved condition in 1 organ, but no change in another organ.
“Steroid-refractory acute graft-versus-host disease can have significant, wide-ranging health consequences, including damage to multiple organs, reduced quality of life and risk of death in affected patients,” Nicole Verdun, MD, the director of the Office of Therapeutic Products at CBER, added to the statement.1 “The FDA remains dedicated to helping address the urgent unmet needs of individuals with debilitating and deadly diseases, and today’s approval is an important step in that effort.”
Timeline of Events for Remestemcel-L
- May 2019: Mesoblast submits a rolling BLA for remestemcel-L.
- October 2020: Mesoblast receives CRL recommending additional studies and scientific rationale for potency measurements.
- October 2022: Mesoblast agrees with FDA on additional data and CMC issues, and submits new information.
- February 2023: Mesoblast resubmits the BLA for remestemcel-L.
- March 2023: FDA accepts the resubmission for filing.
- August 2023: FDA issues another CRL requiring more data for marketing approval. Mesoblast announces plans for A study in high-risk adults with SR-aGVHD.
- September 2023: Mesoblast reports outcomes from a Type A meeting with the FDA, establishing the path forward.
- March 2024: FDA informs Mesoblast that data from the phase 3 MSB-GVHD001 clinical trial is sufficient for BLA submission for remestemcel-L in children with SR-aGVHD. Mesoblast plans to submit the BLA in the second quarter of 2024.
- July 2024: Mesoblast resubmits BLA again and the FDA accepts it. A Prescription Drug User Fee Act goal date of January 7, 2025, is assigned by the agency.
- December 2024: Remestemcel-L is approved by the FDA for the treatment of steroid refractory acute GvHD in children aged 2 months or older.
With regard to safety, the FDA notes that the most common adverse reactions in the trial constituted infections, fever, hemorrhage, edema, abdominal pain, and hypertension. Patients receiving remestemcel-L should receive pretreatment with corticosteroids and antihistamines and be monitored for hypersensitivity reactions, dyspnea, hypotension, fever, tachypnea, cyanosis, and hypoxia, according to the agency. Furthermore, the FDA notes that acute infusion reactions, transmission of infectious agents, and ectopic tissue formation may occur in patients who have been treated with the therapy.
Previously reported data from MSB-GVHD001 that were current as of November 2022 demonstrated a long-term survival benefit in treated children through 4 years.5 Treated children had an overall survival (OS) rate of 63% at 1 year, 51% at 2 years, and 49% at 4 years (median, 2-3 years) in comparison with control data in children and adults (using best available therapy or ruoxitinib for adults) in which the OS rate ranged from 40% to 49% at 1 year and 25% to 38% at 2 years (median, 6.5-11.1 months). Furthermore, in the therapy’s favor, 88% of these children had severe disease with the highest risk of mortality—defined by either International Bone Marrow Transplant Registry Grade C/D or Glucksberg Grade 3/4—compared with 22% to 68% of patients in control studies having severe disease.
REFERENCES
1. FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease. News release. FDA. December 18, 2024. Accessed December 18, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host
2. FDA accepts Mesoblast’s biologics license application (BLA) for Ryoncil® in children with steroid-refractory acute graft-versus host disease (SR-aGVHD). Accessed December 18, 2024. https://investorsmedia.mesoblast.com/static-files/9a696437-abbb-4183-822f-9f74c1da5504
3. United States Food & Drug Administration (FDA) notifies mesoblast that available clinical data from phase 3 trial appear sufficient to support BLA submission for remestemcel-L in children with steroid refractory acute graft versus host disease (SR-aGVHD). News release. Mesoblast Limited. March 25, 2024. Accessed December 18, 2024. https://investorsmedia.mesoblast.com/static-files/cbb18b5c-3dea-42bf-877d-599dcc242c44
4. Mesoblast receives complete response from U.S. Food and Drug
Administration for biologics license application for steroid refractory acute graft versus host disease in children. News release. Mesoblast Limited. Accessed December 18, 2024. https://investorsmedia.mesoblast.com/static-files/422cd6da-a0b9-49cf-a177-7fd106f111f2
5. Mesoblast provides update following meeting with FDA’S OTAT on remestemcel-L for children with acute graft versus host disease. News release. Mesoblast. December 30, 2021. Accessed December 18, 2024. https://investorsmedia.mesoblast.com/static-files/71f7b715-a029-47dc-af8e-8c8f09a4a96f
