Refractory Acute Graft Versus Host Disease

NEW YORK, NY, USA I December 18, 2024 I Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced the Food and Drug Administration (FDA) approved Ryoncil ® (remestemcel-L) as the first mesenchymal stromal cell (MSC) therapy in the United States. RYONCIL is the only MSC therapy approved in the U.S. for any indication, and the only approved therapy for steroid-refractory acute graft versus host disease (SR-aGvHD) in children 2 months and older, including adolescents and teenagers. Transplant physician Dr Joanne Kurtzberg, the Jerome Harris Distinguished Professor of Pediatrics and Professor of Pathology, and Director, Marcus Center for Cellular Cures at Duke University Medical Center (DUMC), said: “Steroid-refractory acute graft versus host disease is a devastating condition with an extremely poor prognosis. From today we are able to offer RYONCIL, the first FDA-approved treatment which will be life saving for so many children and will have a great impact on their families.” Annually in the United States approximately 10,000 patients undergo an allogeneic bone marrow transplant, 1,500 of whom are children. Approximately 50% develop aGvHD and almost half of those do not respond to steroids, the recognized first-line treatment. 1-5 In a single-arm multi-center Phase 3 trial of children with SR-aGvHD, 89% of whom had high severity Grade C or Grade D disease, 70% achieved an overall response by Day 28 of treatment with RYONCIL, a measure that predicts survival in aGVHD. RYONCIL treatment was not discontinued or interrupted in any patient for any laboratory abnormality, and the full course was completed without interruption in more than 85% of patients. The full Phase 3 clinical study results are available in Biology of Blood and Marrow Transplantation . 6 “We are very pleased that the FDA has granted approval of RYONCIL ® and are proud of the company’s commitment to the GVHD community in bringing this important new treatment to children and families with no other acceptable options,” said Dr. Silviu Itescu, Chief Executive of Mesoblast. “With RYONCIL approval by FDA, Mesoblast has demonstrated the ability to bring the first MSC product to market. We will continue to work closely with FDA to obtain approval of our other late-stage products, including REVASCOR ® for cardiovascular diseases and rexlemestrocel-L for inflammatory pain indications, as well as expanding the indications for RYONCIL in both children and adults with inflammatory conditions.” RYONCIL will be available in the United States at transplant centers and other treating hospitals. Please see the full Prescribing Information at www.ryoncil.com . The FDA’s approval press release is available here . What is RYONCIL (remestemcel-L) RYONCIL is an allogeneic 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. The recommended dosage of RYONCIL is 2 × 10 6 MSC /kg body weight per intravenous infusion given twice per week for 4 consecutive weeks. Response is assessed 28 ± 2 days after the first dose and further treatment administered as appropriate. Important Safety Information Contraindications: Known hypersensitivity to dimethyl sulfoxide (DMSO) or porcine and bovine proteins. Adverse reactions: Serious adverse reactions included pyrexia (9%), respiratory failure (9%), pneumatosis intestinalis (7%) and staphylococcal bacteremia infection (<5%). Adverse reactions of Grade 3 occurring in ≥10% of patients were viral infectious disorders (15%), bacterial infectious disorders (19%), and infections pathogen unspecified (15%). No grade 4 or 5 adverse reactions occurred in the study. Eight patients had discontinuation of RYONCIL treatment due to the following: acute infusion reactions (n=3), hypotension (n=1), gastroenteritis (n=1), and death (n=3). You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . You may also report side effects to Mesoblast at toll-free phone #1-844-889-MESO (6376) Please see the RYONCIL full Prescribing Information for additional Important Safety Information. 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 therapies from the Company’s proprietary mesenchymal lineage cell therapy technology platform 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. Mesoblast’s RYONCIL ® (remestemcel-L) for the treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in children 2 months and older is the first FDA-approved mesenchymal stromal cell (MSC) therapy. Mesoblast is committed to developing additional cell therapies for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. RYONCIL is being developed for additional inflammatory diseases including SR-aGvHD in adults and biologic-resistant inflammatory bowel disease. Rexlemestrocel-L is being developed for heart failure and chronic low back pain. The Company has established commercial partnerships in Japan, Europe and China. About Mesoblast intellectual property: Mesoblast has a strong and extensive global intellectual property portfolio, with over 1,000 granted patents or patent applications covering mesenchymal stromal cell compositions of matter, methods of manufacturing and indications. These granted patents and patent applications provide commercial protection extending through to at least 2041 in all major markets. About Mesoblast manufacturing: 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. Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com , LinkedIn: Mesoblast Limited and Twitter: @Mesoblast References / Footnotes SOURCE: Mesoblast

The therapy is also under development for SR-aGvHD in adults and biologic-resistant inflammatory bowel disease. Credit: PowerUp/Shutterstock. Mesoblast has gained US Food and Drug Administration (FDA) approval for its mesenchymal stromal cell (MSC) therapy, Ryoncil (remestemcel-L), to treat steroid-refractory acute graft versus host disease (SR-aGvHD) in paediatric patients aged a minimum of two months and up to adolescents and teenagers. It is the only MSC therapy approved in the US for any indication. Ryoncil is part of a development programme for inflammatory diseases such as SR-aGvHD in adults, and biologic-resistant inflammatory bowel disease. Other therapies, such as rexlemestrocel-L, are being developed for conditions such as chronic lower back pain and heart failure. The company has established commercial partnerships for these therapies in China, Japan and Europe. Mesoblast chief executive Dr Silviu Itescu stated: “We are very pleased that the FDA has granted approval of Ryoncil and proud of the company’s commitment to the GVHD community in bringing this important new treatment to children and families with no other acceptable options. “With RYONCIL’s approval by the FDA, Mesoblast has demonstrated the ability to bring the first MSC product to market. We will continue to work closely with the FDA to obtain approval of our other late-stage products, including REVASCOR for cardiovascular diseases and rexlemestrocel-L for inflammatory pain indications, as well as expanding the indications for RYONCIL in both children and adults with inflammatory conditions.” The mesenchymal lineage cell therapy technology platform of the company is designed to respond to severe inflammation with the release of anti-inflammatory factors. These factors counter and modulate multiple effector immune system arms, leading to a reduction in the damaging inflammatory process. In the US, the therapy will be available at hospitals and transplant centres. 10,000 individuals in the US undergo an allogeneic bone marrow transplant annually, of whom 1,500 are paediatric patients. Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content.

On December 18, 2024, the Food and Drug Administration approved remestemcel-L-rknd (Ryoncil, Mesoblast, Inc.), an allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy, for 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.Full prescribing information for Ryoncil will be posted hereEfficacy and SafetyEfficacy was evaluated in MSB-GVHD001 (NCT02336230), a multicenter, prospective, single-arm study in 54 pediatric patients with SR-aGVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Patients had Grade B to D SR-aGVHD, excluding Grade B skin alone (International Blood and Marrow Transplantation Registry Severity Index Criteria). SR-aGVHD was defined as aGVHD progressing within 3 days or not improving within 7 consecutive days of methylprednisolone (2 mg/kg/day or equivalent). Patients receiving a second-line aGVHD therapy prior to screening were excluded.The main efficacy outcome measures were overall response rate (ORR) at Day 28 and duration of overall response. The ORR included complete and partial response rates (CR and PR). ORR at Day 28 was 70% (95% confidence interval, CI: 56.4, 82.0), including a CR rate of 30% (95% CI: 18.0, 43.6) and a PR rate of 41% (95% CI: 27.6, 55.0). The median duration of response calculated from response at Day 28 to either progression, new systemic therapy for aGVHD, or any cause death, was 54 days (range 7, 159+).The most common nonlaboratory adverse reactions (incidence ≥20%) were viral infectious disorders, bacterial infectious disorders, infection – pathogen unspecified, pyrexia, hemorrhage, edema, abdominal pain and hypertension.The recommended dose is 2 X 106 MSC/kg body weight per intravenous infusion given twice a week for 4 consecutive weeks for a total of 8 infusions. Infusions are administered at least 3 days apart. Treatment may be continued based on response at 28 days after initial remestemcel-L-rknd.Expedited ProgramsRemestemcel-L-rknd has fast track, orphan drug and priority review designations. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. A description of FDA expedited programs for regenerative medicine advanced therapies is in the Guidance for Industry: Expedited Programs for Regenerative Medicine Therapies for Serious Conditions.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.For assistance with single-patient INDs for investigational oncology products regulated by the Center for Biologics Evaluation and Research, healthcare professionals may email OTPRPMS@fda.hhs.gov.Follow the Oncology Center of Excellence on X: @FDAOncology.