Remestemcel-L BLA Is Resubmitted for Steroid-Refractory aGVHD

FDA

The biologics license application (BLA) seeking the approval of remestemcel-L (Ryoncil) for the treatment of pediatric patients with steroid-refractory, acute graft-vs-host-disease (SR-aGVHD) has been resubmitted to the FDA.¹

The latest filing, which addressed lingering chemistry, manufacturing, and control items, was made after the FDA informed the agent’s developer, Mesoblast, that the available data from the phase 3 MSB-GVHD001 trial (NCT02336230) were enough to warrant another submission of the BLA in the proposed population.

If the BLA is accepted, the regulatory agency will have between two and six months for review.

“We have worked closely with the agency and thank them for their ongoing guidance, facilitating the potential approval of [remestemcel-L] and addressing the urgent need for a therapy that improves the dismal survival outcome in children with SR-aGVHD,” Silviu Itescu, MBBS, FRACP, chief executive officer of Mesoblast, said in a news release.

In April 2020, the FDA granted priority review to the initial BLA for remestemcel-L for the treatment of this population based on pooled data from 3 separate trials of 309 children with SR-aGVHD.²

In August 2020, the FDA’s Oncologic Drugs Advisory Committee voted 8 to 2 in favor of approving remestemcel-L in this setting after discussing whether data from the single-arm MSB-GVHD001 trial (NCT02336230) were sufficient to establish the efficacy of the drug.³

However, in October 2020, the FDA issued a complete response letter to Mesoblast, requesting additional data from at least 1 randomized, controlled study in adult and/or pediatric patients with SR-aGVHD.⁴

The phase 3 MSB-GVHD001 trial evaluated remestemcel-L in 54 children predominantly with grade C or D SR-aGVHD in the United Stated.1 To be eligible for enrollment, patients had to be between the ages of 2 months and 17 years with a diagnosis of aGVHD. Prior allogeneic hematopoietic stem cell transplant was required, as was treatment failure with systemic corticosteroid therapy. Patients could have had grade C or D disease involving the skin, liver and/or gastrointestinal (GI) tract, or grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease.⁵

The trial met its prespecified primary end point, with an overall response rate (ORR) of 70.4% at day 28 vs a prespecified control ORR value of 45% (P =.0003), which correlated with improved survival through day 100 (87% vs 47% in patients who did not achieve day-28 response; P =.0001).¹

Additional data from a matched control group of pediatric patients from the Mount Sinai Acute GVHD International Consortium (MAGIC) database who received best available therapy showed that remestemcel-L led to higher day-28 ORRs (70% vs 43%) and higher day-100 survival rates (74% vs 57%).

Furthermore, a propensity-matched study of outcomes in 25 children from Mesoblast’s phase 3 trial and 27 children who received best available treatment, including ruxolitinib (Jakafi), from the MAGIC database indicated that 67% of high-risk children with MAP scores above 0.29 who received remestemcel-L achieved a day-28 overall response and were alive after 180 days vs 10% of children in both categories in the MAGIC group.

Regarding durability, results of an observational cohort, 4-year survival study performed by the Center for International Blood and Marrow Transplant Research on 51 evaluable patients with SR-aGVHD who were enrolled in the phase 3 trial demonstrated that the 6-month, 1-year, and 2-year survival rates of 67%, 63%, and 51%, respectively. Additionally, 49% of patients were alive past 4 years, a population with an expected 2-year survival of between 25% and 38% with best available therapy.

References

1. Mesoblast resubmits biologics license application (BLA) with United States Food & Drug Administration (FDA) for approval of Ryoncil in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD). News release. BioSpace. July 9, 2024. Accessed July 9, 2024. https://investorsmedia.mesoblast.com/static-files/444c633b-8319-4159-970f-62be8e01ea97
2. FDA accepts Mesoblasts biologics license application for Ryoncil and agrees to priority review. News release. Mesoblast Limited. April 1, 2020. Accessed July 9, 2024. https://investorsmedia.mesoblast.com/static-files/1ee6fcd5-de79-4645-bc09-1f1fe8864047
3. Baird K. FDA session on clinical evidence: BLA 125706: Remestemcel-L. August 13, 2020. Accessed July 9, 2024. https://www.fda.gov/media/141131/download
4. Mesoblast receives complete response letter from the FDA for biologics license application for steroid-refractory acute graft versus host disease in children. News release. Mesoblast Limited. October 2, 2020. Accessed July 9, 2024. https://investorsmedia.mesoblast.com/static-files/1e259fcb-77ba-470c-91af-1c71e5fa32e0
5. A prospective study of remestemcel-L, ex-vivo cultured adult human mesenchymal stromal cells, for the treatment of pediatric participants who have failed to respond to steroid treatment for acute graft-versus-host disease (aGVHD). ClinicalTrials.gov. Updated March 17, 2022. Accessed July 9, 2024. https://clinicaltrials.gov/study/NCT02336230