Mesoblast, Inc.

SILVER SPRING, Md., Dec. 18, 2024 /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. It contains MSCs, which are a type of cell that can have various roles in the body and can differentiate into multiple other types of cells. These MSCs are isolated from the bone marrow of healthy adult human donors. "Today's decision marks an important milestone in the use of innovative cell-based therapies to treat life-threatening diseases with devastating impacts on patients, including children," said Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research (CBER). "This first mesenchymal stromal cell therapy approval demonstrates the FDA's commitment to supporting the development of safe and effective products that could improve the quality of life for patients with symptoms that are unresponsive to other therapies." Steroid-refractory acute graft-versus-host disease is a serious and life-threatening condition that can occur as a complication of allogeneic hematopoietic (blood) stem cell transplantation (allo-HSCT). In allo-HSCT, a patient receives hematopoietic stem cells from a healthy donor to replace their own stem cells and form new blood cells, a procedure often done as part of treatment for certain types of blood cancers, blood disorders or immune system disorders. "Steroid-refractory acute graft-versus-host disease can have significant, wide-ranging health consequences, including damage to multiple organs, reduced quality of life and risk of death in affected patients," said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. "The FDA remains dedicated to helping address the urgent unmet needs of individuals with debilitating and deadly diseases, and today's approval is an important step in that effort." 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. Ryoncil's effectiveness was based primarily on the rate and duration of response to treatment 28 days after initiating Ryoncil. Study participants who had a partial or mixed response to treatment—meaning that there was improved condition in one organ with either no change (partial) or worsening condition (mixed) in another organ—received additional infusions once weekly for an additional four weeks. Sixteen study participants (30%) had a complete response to treatment 28 days after receiving Ryoncil, while 22 study participants (41%) had a partial response. Infusion of Ryoncil should be monitored by the treating physician, and the infusion should be discontinued if there is any evidence of a reaction which may include dyspnea (shortness of breath), hypotension (low blood pressure), fever, tachypnea (rapid breathing), cyanosis (blue discoloration of skin, lips or nails) and hypoxia (low oxygen in the blood). The most common adverse reactions in study participants who received Ryoncil were infections, fever, hemorrhage, edema, abdominal pain and hypertension. Complications such as hypersensitivity and acute infusion reactions, transmission of infectious disease or agents and ectopic tissue formation may occur following treatment with Ryoncil. Ryoncil is contraindicated in patients with known hypersensitivity to dimethyl sulfoxide or porcine and bovine proteins. Patients should be premedicated with corticosteroids and antihistamines prior to infusion and monitored for hypersensitivity reactions during treatment with Ryoncil. The application received Orphan Drug, Fast Track and Priority Review designations by the FDA. The FDA granted approval of Ryoncil to Mesoblast, Inc. Media Contact: Carly Pflaum, (240) 672-8872 Consumer Inquiries: Email or 888-INFO-FDA The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products. SOURCE U.S. Food and Drug Administration WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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.

Physician-scientists announced today the results of the largest cell therapy trial to date in patients with chronic heart failure due to low ejection fraction. The therapy benefited patients by improving the heart's pumping ability, as measured by ejection fraction, and reducing the risk of heart attack or stroke, especially in patients who have high levels of inflammation. Also, a strong signal was found in the reduction of cardiovascular death in patients treated with cells. Physician-scientists at The Texas Heart Institute announced today the results of the largest cell therapy trial to date in patients with chronic heart failure due to low ejection fraction. The therapy benefited patients by improving the heart's pumping ability, as measured by ejection fraction, and reducing the risk of heart attack or stroke, especially in patients who have high levels of inflammation. Also, a strong signal was found in the reduction of cardiovascular death in patients treated with cells. The findings are published in the Journal of the American College of Cardiology. Investigators in this landmark clinical trial have shown that a special immunomodulatory cell-type called MPC (mesenchymal precursor cells) developed by Mesoblast Inc., has the potential for the first time to address a major contributor to heart failure -- inflammation. Patients in the trial were on full guideline-recommended drug therapy for heart failure, suggesting that the effect of the cell therapy was synergistic with and additive to state-of-the-art heart failure medications. More than 6 million Americans have chronic heart failure, a progressive disease that leads to a weakening of the heart muscle and a loss of its pumping function. Most heart failure drugs used today are aimed at addressing the detrimental changes that occur in the heart as a result of complex neurohormonal pathways that are activated during heart failure to compensate for poor heart function. These activated pathways eventually contribute to the progression of heart failure and repeated hospitalizations. Despite advances in therapies targeting these pathways, mortality rates remain high. The unique mechanism of action of MPC appears to provide an alternative approach that has the potential to make a significant impact on the high mortality of this disease. DREAM-HF (Double-Blind Randomized Assessment of Clinical Events With Allogeneic Mesenchymal Precursor Cells in Heart Failure), sponsored by Mesoblast, was a phase 3 trial performed at 51 sites in 565 patients with chronic heart failure, who were also on standard-of-care heart failure treatment. The study, which had a mean follow-up of 30 months, was designed to examine the effects of MPC comprising immunoselected, culture-expanded mesenchymal precursor cells (MPCs), on the number of hospitalizations and major adverse cardiovascular events in heart failure. MPCs are a good candidate for use in heart failure with low ejection fraction because they have potent anti-inflammatory, pro-angiogenic, and pro-healing effects. The cells were obtained from the bone marrow of healthy adult donors. Cell-treated patients in the study received direct cardiac injections of MPCs, and control patients underwent a "sham" or mock procedure with no injections. MPC-treated patients showed significant strengthening of the left ventricular muscle within the first 12-months as measured by an increase in left ventricular ejection fraction, which measures the heart's pumping ability and is one of the metrics used to assess overall heart function. Over a mean follow-up of 30-months, treatment with MPCs reduced the risk of cardiovascular death, heart attack, or stroke, with a greater decrease in patients with increased inflammation. MPC treatment reduced the rate of heart attack or stroke by 58%, and the benefit rose to 75% in patients who had high levels of a blood marker for inflammation. Similarly to what was seen with these major adverse cardiovascular events, improvement in ejection fraction was even more pronounced in patients with higher inflammation levels. MPC therapy did not further reduce recurrent heart failure events requiring hospitalization over and above the effects of traditional drugs which reduce circulating volume overload caused by the maladaptive effects of neurohormonal activation. This aspect of heart failure treatment is already addressed by the currently available medications. "The results of DREAM-HF are an important step in understanding how cell therapy provides benefits in patients with chronic heart failure due to poor pump function. The cells appear to work by reducing inflammation, increasing microvascular flow, and strengthening heart muscle. Locally, in the heart, the MPCs can protect cardiac muscle cells from dying and can improve blood flow and energetics. In large blood vessels throughout the body, the reduced inflammation resulting from the activation of MPCs may decrease plaque instability, which is what leads to heart attacks and strokes. The cells seem to have a systemic immune modulatory and anti-inflammatory effect," according to the study's lead author, Dr. Emerson C. Perin, MD, PhD, FACC, Medical Director at The Texas Heart Institute. The DREAM-HF findings of long-term improvements in outcomes for patients with chronic heart failure due to low ejection fraction and poor pump function are an important milestone in the field of cell therapy for cardiovascular disease. The results help in identifying those heart failure patients with inflammation who are at greatest risk and most likely to benefit from MPC therapy and findings will be confirmed in future studies. This seminal trial sets the stage for eventually adding cell therapy to the treatment arsenal for heart failure. "The Texas Heart Institute has spent two decades pioneering the development of cellular therapies for the heart and continues to lead the world in this breakthrough work. For millions of people in the United States over the age of 20 who suffer from heart failure, MPC therapy could change the future of cardiovascular care for patients with heart failure due to inflammation," according to Dr. Joseph G. Rogers, CEO and President of The Texas Heart Institute and advanced heart failure specialist.