Remestemcel-L
- Generic Name
- Remestemcel-L
- Drug Type
- Biotech
- Unique Ingredient Identifier
- H57D26Z9YK
- Background
Remestemcel-L is a third-party, off-the-shelf suspension of ex-vivo cultured adult human mesenchymal stem cells intended for intravenous infusion. The mesenchymal stem cells are derived from the bone marrow of unrelated and human leukocyte antigen (HLA)–unmatched healthy adult donors and have the ability to differentiate into different tissue cells. It was approved for use in Canada in May 2012 as Prochymal for the management of refractory acute Graft versus Host Disease (aGvHD) in children who are unresponsive to systemic steroid therapies, with the approval conditional upon further trials being conducted.
aGvHD is a T-cell mediated disease that occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues developed by 30-80% of the recipients . aGvHD is often characterized by the presence of inflammatory cascades through signalling of activated T cells. While systemic corticosteroids and other immunosuppressive agents are commonly used as first-line treatments to manage aGvHD, about 30-50% of patients with aGvHD experience inadequately control of disease with first-line therapies, putting them in a risk for poor outcomes and creating a significant clinical challenge . It is estimated that the patients with the most severe forms of refractory aGvHD that do not respond to steroid therapy have expected one-year survival rates of only 5% to 30% . Human mesenchymal stem cells (hMSCs) serve to down-regulate inflammatory responses and produce anti-inflammatory cytokines and growth factors to promote tissue repair . In clinical studies, patients treated with remestemcel-L demonstrated an improvement in their aGvHD and improved survival rates at subsequent days following intravenous infusion . Based on its tolerability and safety profile, remestemcel-L is a promising alternative to second-line immunosuppressive agents .
- Indication
Indicated for in the management of acute Graft versus Host Disease (aGvHD) in pediatric patients. Acute GvHD should be refractory to treatment with systemic corticosteroid therapy and/or other immunosuppressive agents. Remestemcel-L may be used for Grades C and D of the disease in any organ. Remestemcel-L may also be used in the management of Grade B aGvHD involving any visceral organ, including the GI tract and the liver, but excluding skin.
- Associated Conditions
- Acute, refractory Graft Versus Host Disease
FDA Roundup: Approvals, Breakthrough Designations, and Clinical Holds in Neurology and Rare Diseases
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FDA Approves Ryoncil, First Mesenchymal Stromal Cell Therapy for Pediatric Steroid-Refractory Acute Graft-versus-Host Disease
• The FDA has approved Ryoncil (remestemcel-L-rknd) as the first mesenchymal stromal cell (MSC) therapy for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients.
• Ryoncil's approval was based on a Phase III trial demonstrating a 70% overall response rate in children with SR-aGVHD after 28 days of treatment.
• This allogeneic, bone marrow-derived MSC therapy offers a new treatment option for children with SR-aGVHD who do not respond to steroid treatment.
• Ryoncil is administered intravenously and should be monitored for infusion reactions; common side effects include infections, fever, hemorrhage, and abdominal pain.
FDA Approves Ryoncil, First Mesenchymal Stromal Cell Therapy for Pediatric SR-aGVHD
• The FDA has approved Ryoncil (remestemcel-L) as the first mesenchymal stromal cell (MSC) therapy in the United States.
• Ryoncil is indicated for steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients aged 2 months and older.
• Clinical trials showed a 70% overall response rate by Day 28 in children with SR-aGvHD treated with Ryoncil.
• Ryoncil offers a new treatment option for a life-threatening condition with limited alternatives, improving outcomes for affected children.
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• Clinical trial data showed overall response rates of 40% in pancreatic cancer and 33% in NSCLC, with manageable side effects, supporting the approval.
• This approval highlights the importance of biomarker testing to identify NRG1 fusions, enabling personalized treatment for these difficult-to-treat cancers.
Cell Therapy and Targeted Therapies Dominate Oncology Advances in Early 2025
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Mesoblast Anticipates FDA Decision on Ryoncil for Pediatric SR-aGvHD by January 2025
• Mesoblast anticipates an FDA decision on Ryoncil (remestemcel-L) by January 7, 2025, for treating steroid-refractory acute graft versus host disease (SR-aGvHD) in children under 12.
• The company has secured manufacturing and distribution channels for Ryoncil and completed a Pre-License Inspection by the FDA with no significant regulatory issues.
• Revascor (rexlemestrocel-L) received Rare Pediatric Disease and Orphan-Drug Designation for treating paediatric congenital heart disease, potentially leading to FDA incentives.
• Mesoblast reported reduced operating cash outflows and a solid cash balance, supported by financing facilities contingent on Ryoncil's approval, alongside cost-control measures.
Mesoblast Awaits FDA Decision on Ryoncil for Pediatric SR-aGvHD
• Mesoblast anticipates FDA decision on Ryoncil (remestemcel-L) by January 7, 2025, for treating steroid-refractory acute graft versus host disease (SR-aGvHD) in children.
• The company has secured manufacturing and distribution channels for Ryoncil, completing an FDA Pre-License Inspection with no significant regulatory issues.
• Revascor (rexlemestrocel-L) received Rare Pediatric Disease and Orphan-Drug Designation for paediatric congenital heart disease, advancing other clinical programs.
• Mesoblast reduced net operating cash outflows by 26% year-over-year, with US$51.1m in cash reserves and access to US$60m in financing upon Ryoncil's approval.
Mesoblast Anticipates FDA Decision on Ryoncil for Pediatric SR-aGVHD by January 7, 2025
• Mesoblast's Biologics License Application (BLA) for Ryoncil (remestemcel-L) in children with steroid-refractory acute graft versus host disease (SR-aGVHD) is under FDA review, with a PDUFA date of January 7, 2025.
• Strategic financing is in place, including a potential US$50 million convertible note agreement, to support the commercial launch of Ryoncil upon FDA approval.
• A Phase 3 trial has commenced for rexlemestrocel-L in chronic low back pain due to inflammatory degenerative disc disease, with FDA agreement on trial design and endpoints.
Oncology Drug Development Pipeline Remains Robust, Driven by Novel Therapies and Cell Therapies
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• Cell therapies for solid tumors are gaining traction, with 44% of all trials initiated in 2023 focusing on solid tumor indications, marking a significant trend in oncology.
• Recent FDA approvals include targeted therapies like inavolisib for HER2-negative breast cancer and repotrectinib for NTRK-positive solid tumors, alongside immunotherapies and bispecific antibodies.
Mesoblast Secures $50 Million Funding Option Contingent on Ryoncil FDA Approval
• Mesoblast has entered into a convertible note agreement with its largest shareholder for up to $50 million, pending FDA approval of Ryoncil.
• The funding will support the commercial launch of Ryoncil for treating children with steroid-refractory acute graft versus host disease (SR-aGvHD).
• The convertible notes have a 5% annual coupon and a conversion price of $9.06 per American Depository Receipt (ADR).
• FDA decision on Ryoncil is anticipated by January 7, 2025, which aligns with Mesoblast's commercialization strategy.
Mesoblast's Ryoncil Nears Potential FDA Approval for Pediatric Graft-versus-Host Disease
• Mesoblast's remestemcel-L (Ryoncil) has a PDUFA date of January 7, 2025, for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients.
• If approved, Ryoncil would be the first treatment option for children under 12 with SR-aGVHD, addressing a critical unmet need in this vulnerable population.
• Industry analysts maintain a consensus Buy rating for Mesoblast, with an average price target of $11, representing a 56% upside potential.
FDA's July Roundup: Approvals, Fast Tracks, and Designations in Oncology
• The FDA approved FoundationOne Liquid CDx as a companion diagnostic for niraparib and abiraterone in BRCA-mutated metastatic castration-resistant prostate cancer.
• Several therapies received fast track designations, including OBX-115 for advanced melanoma and ADI-270 for metastatic clear cell renal cell carcinoma.
• Biologics license applications were accepted for remestemcel-L in pediatric steroid-refractory acute graft-vs-host disease and tabelecleucel for Epstein-Barr virus-positive posttransplant lymphoproliferative disease.
• The Oncologic Drugs Advisory Committee voted to require comprehensive phase assessments for new trial designs in perioperative regimens for non-small cell lung cancer.
FDA Accepts Resubmitted BLA for Remestemcel-L in Pediatric Steroid-Refractory Acute GVHD
• The FDA has accepted Mesoblast's resubmitted Biologics License Application (BLA) for remestemcel-L (Ryoncil) to treat pediatric steroid-refractory acute graft-vs-host disease (SR-aGVHD).
• The resubmission addresses chemistry, manufacturing, and control (CMC) issues, with the FDA considering prior clinical data from the Phase 3 MSB-GVHD001 trial as sufficient.
• The PDUFA goal date for the FDA's decision on remestemcel-L is set for January 7, 2025, offering potential hope for children with limited treatment options.
• Phase 3 trial data showed remestemcel-L achieved a 70.4% overall response rate at day 28, significantly higher than the pre-specified 45% (P = .0003).
FDA Grants Fast Track Designation to Remestemcel-L for COVID-19 ARDS Treatment
• The FDA has granted Fast Track designation to remestemcel-L for treating acute respiratory distress syndrome (ARDS) due to COVID-19, addressing a critical unmet need.
• Clinical data from a pilot study showed that 75% of ventilator-dependent COVID-19 ARDS patients were successfully discharged after remestemcel-L treatment.
• A Phase 3 trial is ongoing, evaluating remestemcel-L in up to 300 ventilator-dependent patients with moderate to severe COVID-19 ARDS, with mortality as the primary endpoint.
• Mesoblast has partnered with Novartis for the development, manufacturing, and commercialization of remestemcel-L, initially focusing on ARDS treatment.
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