Mesoblast Resubmits BLA to US FDA for Approval of Ryoncil in Children with SR-aGVHD

Mesoblast Resubmits BLA to US FDA for Approval of Ryoncil in Children with SR-aGVHD

By, Admin 9 July 2024

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)

Overview

Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, announced today it has resubmitted its BLA for approval of Ryoncil® (remestemcel-L) in the treatment of children with SR-aGVHD.

BLA by Mesoblast

The filing comes after Mesoblast was informed by FDA at the end of March that, following additional consideration, the available clinical data from the Phase 3 study MSB-GVHD001 appears sufficient to support submission of the proposed BLA for remestemcel-L for treatment of pediatric patients with SR-aGVHD. As a result, the filing addresses remaining CMC (Chemistry, Manufacturing, and Control) items.

Statement from The CEO: Mesoblast

We have worked closely with the agency and thank them for their ongoing guidance, facilitating the potential approval of RYONCIL and addressing the urgent need for a therapy that improves the dismal survival outcome in children with SR-aGVHD,” said Mesoblast CEO Dr. Silviu Itescu.

FTD for Remestemcel-L

  • FDA granted remestemcel-L Fast Track designation, a process to facilitate the development and expedited review of therapies for serious conditions that fill unmet medical needs, and Priority Review designation, which is given to drugs that treat a serious condition and provide a significant improvement in safety or effectiveness over existing treatments. 
  • The BLA resubmission upon acceptance is expected to have a review period of between two and six months from receipt.

About Ryoncil® (remestemcel-L)

  • Mesoblast’s lead product candidate, Ryoncil® (remestemcel-L), is an investigational therapy comprising culture expanded mesenchymal stromal cells derived from the bone marrow of an unrelated donor. 
  • It is administered to patients in a series of intravenous infusions. 
  • RYONCIL has immunomodulatory properties which counteract the inflammatory processes that are implicated in SR-aGVHD by inhibiting activation and proliferation of effector T cells, down-regulating the production of pro-inflammatory cytokines, and enabling recruitment of anti-inflammatory cells to involved tissues.

About the Phase 3 Trial of Ryoncil® (remestemcel-L) in Children with Steroid-Refractory Acute Graft Versus Host Disease

  • The Phase 3 Study GVHD001/002 was conducted in 54 children (89% Grade C/D) across 20 centers in the US where RYONCIL was used as the first line of treatment for children who failed to respond to steroids for acute GVHD.1 
  • The trial met its pre-specified primary endpoint, Day 28 Overall Response (OR), 70.4% versus 45%, p=0.0003. 
  • An overall response at day 28 was highly predictive of improved survival through day 100 (87% compared to 47% in patients that did not achieve day 28 OR p= 0.0001).

Ryoncil Studies Outcomes

  • Compared with a matched control group of pediatric subjects from the contemporaneous database of the Mount Sinai Acute GVHD International Consortium (MAGIC) treated with best available therapy, treatment with Ryoncil achieved higher Day 28 OR (70% vs 43%) and higher Day 100 survival (74% vs 57%). 
  • A propensity-matched study of outcomes in 25 children from Mesoblast’s Phase 3 trial and 27 control children who received best available treatment, including ruxolitinib, from the MAGIC database showed that 67% of high-risk children (MAP scores >0.29) who received Ryoncil achieved a Day 28 overall response and were alive after 180 days compared to just 10% in both categories in the MAGIC group.

4-Year Survival Study Results

In addition, results of a 4-year survival study performed by the Center for International Blood and Marrow Transplant Research (CIBMTR) on 51 evaluable patients with SR-aGVHD who were enrolled in the Phase 3 trial, demonstrated durability of the survival benefits, with 67% survival at 6 months, 63% survival at 1 year, 51% at 2 years, and 49% survival through 4 years in children with expected 2 year survival of just 25-38% using best available therapy.2-4

About Steroid-Refractory Acute Graft Versus Host Disease

  • Acute GVHD occurs in approximately 50% of patients who receive an allogeneic bone marrow transplant (BMT). 
  • Over 30,000 patients worldwide undergo an allogeneic BMT annually, primarily during treatment for blood cancers, including about 20% in pediatric patients.
  • SR-aGVHD is associated with mortality as high as 90% and significant extended hospital stay costs.
  • There are currently no FDA-approved treatments in the US for children under 12 with SR-aGVHD.

Survival Outcomes

  • Survival outcomes have not improved over the past two decades for children or adults with the most severe forms of SR-aGVHD.
  • The lack of any approved treatments for children under 12 means that there is an urgent need for a therapy that improves the dismal survival outcomes in children.

About Mesoblast

  • Mesoblast (the Company) is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. 
  • The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of late-stage product candidates which respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process.

Intellectual Property Portfolio: Mesoblast

  • Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. 
  • The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. 
  • These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.

Product Development for Different Indications

  • Mesoblast is developing product candidates for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. 
  • Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease, and biologic-resistant inflammatory bowel disease. 
  • Rexlemestrocel-L is being developed for advanced chronic heart failure and chronic low back pain. 
  • Two products have been commercialized in Japan and Europe by Mesoblast’s licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.

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