Remestemcel-L-rknd

Mesoblast’s stock surged on Thursday after the company won FDA approval for its twice-rejected graft-versus-host disease therapy. Remestemcel-L is the first mesenchymal stromal cell therapy to be approved by the FDA. The drug, branded as Ryoncil, will be available in the coming weeks for pediatric patients 2 months and older with acute graft-versus-host disease, a complication of allogeneic transplant in which donor cells attack the recipient. Ryoncil is specifically approved for patients who do not respond to steroids, the first line of treatment. Ryoncil’s path to market took several turns, with an approval coming more than four years after regulators accepted Mesoblast’s first application. The company’s stock $MESO was up 36% on Thursday afternoon, pricing at nearly $17 per share. “This is a day to celebrate the tremendous work, the commitment and the perseverance of everybody at Mesoblast for these many, many years,” CEO Silviu Itescu said on a call with investors Wednesday night. The company declined to share the list price. Odds of an approval looked good in 2020, when an FDA advisory committee voted 9-1 in favor of Ryoncil. The committee shrugged off concerns that efficacy was determined from a single-arm trial, after struggling to imagine what a randomized trial would look like given parents’ and pediatricians’ reluctance to put children in a placebo arm. The FDA usually follows the recommendations of its advisory committees. But in a rare move, the agency rejected Ryoncil in October 2020 after raising concerns about the trial design during the advisory committee meeting. Regulators also had concerns about potency measurements, following “inconsistent batch-to-batch potency,” Jefferies’ David Stanton said at the time. Itescu told Endpoints on Thursday that the rejection was “primarily focused on ensuring we had a robust potency assay in place that correlated with clinical outcomes, reflected the mechanism of action and would ensure we maintain continued efficacy if we make future manufacturing changes.” Mesoblast resubmitted its application with additional data and analyses, including information on an optimized potency assay . But the company was met with another rejection in August 2023, along with a request for more data. At the time, the company said it would conduct a study in the “highest-risk adults with the greatest mortality” to get the additional data. However, the company didn’t end up needing another study. This time around, Mesoblast said it addressed outstanding chemistry, manufacturing and controls concerns. Upon resubmitting, the company said that after “additional consideration,” the FDA said available data from its single-arm Phase 3 study MSB-GVHD001 in 54 pediatric patients “appears sufficient” to support approval. Itescu said Thursday that the 2023 CRL was also primarily focused on a “robust potency assay.” “The FDA’s concern around the potency assay was around the variability range of results. Mesoblast identified the root cause of the assay variability, standardized the raw materials, improved training, and significantly reduced the standard deviation of the test,” Itescu said in an email.

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