Findings from a phase 3 clinical trial, including data from high-risk children given remestemcel-L, led the FDA to accept the biologics license application of the therapy.
The FDA’s Office of Therapeutic Products has accepted the biologics license application (BLA) resubmission for remestemcel-L for the treatment of children with steroid-refractory acute graft-vs-host disease (SR-aGVHD), according to Mesoblast Limited.
The BLA resubmission from February 2023 includes findings from the phase 3 GVHD001/002 clinical trial (NCT02652130), which showed the durability of the treatment effect through 4 years or more, the treatment benefit in patients with high-risk disease and on survival in propensity-matched studies, and that the validated potency assay has low variability demonstrating consistency and reproducibility for manufacturing.
Additional clinical and biomarker data from a propensity-matched study of children with high-risk disease were included in the study, which are based on the validated MAP biomarker score. The outcomes of 25 children from a phase 3 trial and 27 children in the control group treated with various biologics, including ruxolitinib (Jakafi) from the Mount Sinai Acute GvHD International Consortium (MAGIC) database were evaluated.
Among those enrolled, 67% of high-risk children given remestemcel-L had positive responses to treatment within 28 days and were alive after 180 days vs just 10% in both categories of the MAGIC group.
Also, in the BLA resubmission are the results of a 4-year survival study which was done by the Center for International Blood and Marrow Transplant Research (CIBMTR) and evaluated 51 patients with SR-aGVHD in the phase 3 trial. Findings showed that there was durability of the early day 180 survival benefits, with 63% survival at 1 year and 51% at 2 years for patients with predominantly grade C/D disease (89%) with an expected survival at 2 years of 25%-38% using best available therapy.
“Over the last 2 years we have worked tirelessly to address the issues previously raised by FDA. We look forward to working closely with the agency over the review period with the aim to make remestemcel-L available as a therapy for children suffering from SR-aGVHD,” said Silviu Itescu, chief executive of Mesoblast Limited, in the press release announcing the resubmission.
Previously, the FDA granted a fast-track designation to remestemcel-L, an investigational therapy that is administered via intravenous infusion and made of culture expanded mesenchymal stromal cells from the bone marrow of an unrelated donor. The therapy is believed to have immunomodulatory properties which counteract the inflammatory processes seen in SR-aGVHD by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.
The initial BLA submission consisted of findings and clinical outcomes of 309 children with SR-aGVHD who were administered remestemcel-L, which showed consistent treatment responses and survival across 3 trials. In August 2020, the Oncologic Drugs Advisory Committee (ODAC) of the FDA voted in favor, 9 to 1, that the available data support the use of remestemcel-L in pediatric patients with SR-aGVHD.
If remestemcel-L is approved, it will be the first allogeneic “off-the-shelf” cellular medicine in the United States, as well as the first therapeutic option for children under the age of 12 with SR-aGVHD.
According to the FDA, the resubmission will be a complete response and they have set a Prescription Drug User Fee Act goal date of August 2, 2023.