Ryoncil (remestemcel-L) / Mallinckrodt, Mesoblast, JCR Pharma - LARVOL DELTA

Mesoblast Extends Payer Coverage For Ryoncil to Over 100 Million US Lives (GlobeNewswire) - "Mesoblast...announced that it has continued to expand coverage for Ryoncil (remestemcel-L), the first mesenchymal stromal cell (MSC) therapy approved by U.S. Food and Drug Administration (FDA) for any indication, to 104 million US lives insured by government and commercial payers. To date, 37 of the 51 states provide fee-for-service Medicaid coverage for Ryoncil through Orphan Drug Lists or medical exception / prior authorization (PA) process, representing 20 million covered lives, or 80% of the total Medicaid fee-for-service lives covered. The remainder will come on line July 1, 2025 with mandatory coverage for 24 million lives."

US reimbursement • Acute Graft versus Host Disease

A milestone for the therapeutic EV field: FDA approves Ryoncil, an allogeneic bone marrow-derived mesenchymal stromal cell therapy. (PubMed, Extracell Vesicles Circ Nucl Acids) - "Strategies like immortalizing MSCs and expanding them clonally can improve scalability, consistency, and overcome limitations inherent to cellular MSC therapies. With the FDA's decision signaling significant progress, optimizing MSC expansion protocols and refining potency testing methods will be crucial for advancing MSC-EVs as a viable therapeutic option, overcoming current challenges, and expanding clinical applications."

FDA event • Journal • Acute Graft versus Host Disease • Graft versus Host Disease • Immune Modulation • Immunology • Pediatrics

First Three Children to Commence Treatment With Ryoncil (GlobeNewswire) - "Mesoblast...announced that it has entered into the Medicaid National Drug Rebate Agreement (NDRA) with the U.S. Centers for Medicare & Medicaid Services (CMS), Department of Health and Human Services, for Ryoncil (remestemcel-L), the first mesenchymal stromal cell (MSC) therapy approved by U.S. Food and Drug Administration (FDA) for any indication. The NDRA agreement with Mesoblast means that the U.S. Government now provides inpatient and outpatient access for a treatment course of Ryoncil to the approximately 40% of U.S. children covered by Medicaid who have steroid-refractory acute graft versus host disease (SR-aGvHD), the remainder being covered by private insurance. U.S. states have the option to immediately cover Ryoncil, with mandatory coverage commencing July 1, 2025. The first three children with SR-aGvHD will receive a course of Ryoncil commencing this week."

US reimbursement • Acute Graft versus Host Disease

Ryoncil is Now Available for Purchase in the United States (GlobeNewswire) - "Mesoblast Limited...announced that Ryoncil (remestemcel-L) the first mesenchymal stromal cell (MSC) therapy approved by U.S. Food and Drug Administration (FDA) for any indication, is now available for purchase in the United States. Ryoncil is approved for treatment of pediatric patients 2 months and older, including adolescents and teenagers, with steroid-refractory acute graft versus host disease (SR-aGvHD), a condition with high mortality rates. The recommended dosage of Ryoncil for treatment of pediatric SR-aGvHD is 2×106 MSC/kg body weight per intravenous infusion given twice per week for 4 consecutive weeks."

Launch US • Acute Graft versus Host Disease

Ryoncil Product Information Now Available in All Four Major Drug Pricing Compendia in United States (GlobeNewswire) - "Mesoblast Limited...today announced that pricing information for Ryoncil is now available in all four major drug pricing compendia in the United States. These pricing compendia provide the official source for all information required to order product, including product manufacturing details, National Drug Codes (NDC) for kit purchase, and kit pricing....The pricing compendia listing followed approval and publication by the U.S. Food and Drug Administration (FDA) of the revised Ryoncil label, which includes revisions to Section 16 (How Supplied / Storage and Handling) of the product prescribing information."

Launch US • Pricing • Acute Graft versus Host Disease

Mesoblast Sets Ryoncil Price Based on Economic Value of Treatment With Planned Product Availability This Quarter (GlobeNewswire) - "'Our FDA approved product Ryoncil will be available in the coming weeks to the children with SR-aGvHD in need of life-saving therapy,'...Royalties from sales by our licensees for H1 FY2025 were US$3.2 million compared with US$3.4 million for the comparative period in FY2024. Research & Development expenses were US$20.6 million in H1 FY2025, of which US$8.2 million was due to non-cash share-based payments primarily for STI in lieu of cash-based payments."

Commercial • Launch US • Acute Graft versus Host Disease

Remestemcel-L (Ryoncil) for graft-versus-host disease. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Graft versus Host Disease • Immunology

Ryoncil FDA Approval and Market Launch Highlighted at Tandem Transplantation Meetings (GlobeNewswire) - "Mesoblast Limited...today announced that its recently approved product Ryoncil (remestemcel-L) is being highlighted at the 2025 Transplantation & Cellular Therapy Tandem Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for Blood and Marrow Transplant Research (CIBMTR)...Mesoblast has a significant presence at the Tandem meetings including an information hub to engage with and educate healthcare providers in support of Ryoncil’s upcoming launch, a key presentation by Mesoblast executives of scientific and clinical results for Ryoncil, and hosting two investigator-led advisory panel meetings discussing Ryoncil for acute SR-aGvHD."

Clinical • Acute Graft versus Host Disease • Delayed Sleep Phase Disorder • Immunology • Multiple Sclerosis

ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells. (PubMed, Cytotherapy) - "The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States...The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval. This approval will revive investment and enthusiasm in MSC products, further approvals in major markets, and will continue to foreshadow the long-predicted success of MSCs as a pharmaceutical."

FDA event • Journal • Graft versus Host Disease • Immunology • Pediatrics

Ryoncil (Remestemcel-L) for Third-Line Treatment of SR-aGVHD in Adolescents and Adults (TCT-ASTCT-CIBMTR 2025) - P3 | "Adolescents and adults with SR-aGVHD who do not respond to ruxolitinib or other second line agents have survival of only 25-30% through 100 days. 1,2 In this case series, treatment with RYONCIL as third line therapy in adolescents and adults with SR-aGVHD resulted in substantially improved survival outcomes. These results indicate that RYONCIL in these highest risk patients appears to favorably modify the course of disease preventing early mortality from SR-aGVHD."

Clinical • Acute Graft versus Host Disease • Graft versus Host Disease • Pediatrics

FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease (PRNewswire) - "Today, the U.S. Food and Drug Administration approved Ryoncil (remestemcel-L-rknd), an allogeneic (donor) bone marrow-derived mesenchymal stromal cell (MSC) therapy indicated for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients 2 months of age and older. Ryoncil is the first FDA-approved MSC therapy....The safety and effectiveness of Ryoncil were evaluated in a multicenter, single-arm study in 54 pediatric study participants with SR-aGVHD after undergoing allo-HSCT. Study participants received intravenous infusion of Ryoncil twice weekly for four consecutive weeks, for a total of eight infusions. Each study participant's condition at baseline was analyzed using the International Blood and Marrow Transplantation Registry Severity Index Criteria (IBMTR) to evaluate which organs have been affected and the overall severity of the disease."

FDA approval • Acute Graft versus Host Disease

Appendix 4C Quarterly Activity Report for Quarter Ended September 30, 2024 (GlobeNewswire) - "Ryoncil (Remestemcel-L) for Steroid-Refractory Acute Graft Versus Host Disease – Potential FDA Approval: Mesoblast resubmitted its BLA to FDA for approval of RYONCIL on July 8, 2024 and anticipates a decision prior to or on the FDA’s Prescription Drug User Fee Act (PDUFA) goal date of January 7, 2025."

FDA approval • PDUFA • Acute Graft versus Host Disease

Mesoblast Option to Issue Up to US$50 Million Convertible Notes for Product Launch (GlobeNewswire) - "Mesoblast Limited....today announced it has entered into a convertible note subscription agreement with its largest shareholder Gregory George ('Investor') for issue, at its sole discretion, up to US$50.0 million (A$72.7 million) convertible notes on approval by the United States Food and Drug Administration (FDA) of Mesoblast’s lead product candidate Ryoncil (remestemcel-L) in the treatment of children with steroid-refractory acute graft versus host disease (SR-aGvHD)....The conversion price of the convertible notes will be US$9.06 per ADR (American Depository Receipt) equivalent to A$1.32 per ASX-listed share, representing a 25% premium to Mesoblast’s 5-day volume weighted average share price ('VWAP') up to and including the close of trading on NASDAQ on Friday, September 27th, 2024."

Financing • Acute Graft versus Host Disease

Appendix 4C Quarterly Activity Report for Quarter Ended June 30, 2024 (GlobeNewswire) - "Graft versus Host Disease – Pending Decision on FDA Approval: FDA accepted the BLA resubmission within two weeks, considering it to be a complete response. Mesoblast anticipates a decision prior to or on the FDA’s Prescription Drug User Fee Act (PDUFA) goal date of January 7, 2025....RYONCIL is being reviewed under Priority Review..."

FDA filing • PDUFA • Priority review • Acute Graft versus Host Disease

Breast Cancer Stem Cells Upregulate IRF6 in Stromal Fibroblasts to Induce Stromagenesis. (PubMed, Cells) - "In BCSC xenografts, fibroblast IRF6 expression led to an increase in the stromal area and fibroblast density in tumors, in addition to a reduction in necrotic growth. Based on our findings, we propose that fibroblast IRF6 function is an important factor in the development of the stromal microenvironment and in sustaining the BCSC tumor niche."

Cancer stem • Journal • Stroma • Breast Cancer • Fibrosis • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • CAFs • IRF6

Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma. (PubMed, Drug Resist Updat) - "The critical determinants of therapy resistance include oncogenic signaling and epigenetic modifications that drive cancer cell stemness and metabolic adaptations, CAF-mediated stromagenesis that results in ECM deposition altered mechanotransduction, and secretome and immune evasion. We reviewed the current understanding of these multifaceted mechanisms operating in the PDAC microenvironment, influencing the response to chemotherapy, radiotherapy, and immunotherapy regimens. We then describe how the lessons learned from these studies can guide us to discover novel therapeutic regimens to prevent, delay, or revert resistance and achieve durable clinical responses."

Journal • Review • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies. (PubMed, Sci Transl Med) - "Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure...Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents."

Journal • Gastrointestinal Cancer • Metabolic Disorders • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

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) (GlobeNewswire) - "Mesoblast Limited...announced today it has resubmitted its BLA for approval of Ryoncil (remestemcel-L) in the treatment of children with SR-aGVHD. 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."

FDA filing • Acute Graft versus Host Disease

Mesoblast to File Biologics License Application for Ryoncil FDA Approval Next Week (GlobeNewswire) - "Mesoblast Limited...today confirmed that it will file its Biologics License Application (BLA) for approval of Ryoncil (remestemcel-L) in the treatment of children with steroid-refractory acute graft versus host disease (SR-aGVHD) with the U.S. Food and Drug Administration (FDA) next week"

FDA filing • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Mesoblast Corporate Presentation at Investor Conference (GlobeNewswire) - "Dr. Itescu reiterated that the Company expects to file this quarter the Biologics License Application (BLA) resubmission with the United States Food and Drug Administration (FDA) for its lead product candidate Ryoncil (remestemcel-L) in the treatment of steroid-refractory acute graft versus host disease, with potential approval in the second half of CY2024....On RYONCIL approval, the granted patents may be extended up to 2037. Additional patent filings may extend the commercial barrier to entry through 2043."

FDA filing • Patent • Acute Graft versus Host Disease

After Almost 4 Years, FDA Says Mesoblast Phase 3 Therapy Data Can Support Resubmission For Serious Complications in Children Following Stem Cell Transplant (Yahoo Finance) - "Monday, the FDA informed Mesoblast Limited...that following additional consideration, the available clinical data from its Phase 3 study MSB-GVHD001 appears sufficient to support submission of the proposed Biologics License Application (BLA) for remestemcel-L for pediatric patients with steroid-refractory acute graft versus host disease (SR-aGVHD)....Price Action: MESO shares are up 75.90% at $3.87 on the last check Tuesday."

FDA event • Stock price • Acute Graft versus Host Disease

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) (GlobeNewswire) - "Mesoblast Limited...announced that U.S. FDA has informed the company that following additional consideration the available clinical data from its Phase 3 study MSB-GVHD001 appears sufficient to support submission of the proposed Biologics License Application (BLA) for remestemcel-L for treatment of pediatric patients with steroid-refractory acute graft versus host disease (SR-aGVHD)....Mesoblast intends to file the resubmission during the next quarter, seeking to address all remaining product characterization issues."

BLA • FDA event • Acute Graft versus Host Disease

Efficacy of off-the-shelf bone marrow mesenchymal stem cells for pediatric steroid-refractory acute graft-versus-host disease. (PubMed, Blood Cell Ther) - "Temcell is a mesenchymal stem cell (MSC) product approved for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in Japan...The first MSC cycle displayed the best overall response rate of 83%, including six patients with a complete response (CR) and with a 49% reduction in the mean daily dose of prednisone after eight weeks...MSC therapy appears to be an effective and safe treatment for pediatric SR-aGVHD, with a steroid-sparing effect and satisfactory efficacy upon re-administration. Further studies are needed to determine its appropriate combination with additional treatments and the optimal use of re-administration of MSCs."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Pediatrics • Transplantation

Efficacy of Treatment Options for Children with Steroid-Refractory Acute Gvhd (ASH 2023) - "Only a few small size clinical trials were conducted for children with SR-aGVHD which poses a unique challenge for FDA to approve new therapies for SR-aGVHD. Despite a small number (n=9: 5 ruxolitinib arm and 4 control arm) of children (12-18 years) enrolled in REACH II study, ruxolitinib was FDA approved for children>12 years of age. Long-term efficacy outcomes of children enrolled in clinical trials were reported only for remestemcel-L and showed that approximately half survived beyond 3 years."

Clinical • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Oncology • Pediatrics • Transplantation

Mesoblast Partners With Blood and Marrow Transplant Clinical Trials Network (BMT CTN) on Pivotal Trial in Adults With SR-aGVHD (GlobeNewswire) - "Mesoblast Limited....today announced that the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)...has entered into an agreement to develop a pivotal trial of Mesoblast’s lead product candidate Ryoncil^® (remestemcel-L) in the treatment of adults with steroid-refractory acute graft versus host disease (SR-aGvHD). The BMT CTN is funded by the United States National Institutes of Health (NIH)....'We are delighted to be partnering with Mesoblast in this pivotal Phase 3 trial of RYONCIL, a potentially life-saving treatment for adolescents and adults with the most severe form of aGVHD. The clinical data from children treated with RYONCIL which support this trial are very compelling.'"

Licensing / partnership • Acute Graft versus Host Disease