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Redefine what’s possible in pediatric steroid-refractory acute graft-versus-host disease (SR-aGvHD)

Demonstrated efficacy in pediatric SR-aGvHD patients, including those with high-grade disease (Grade C and D)1-3

In a pivotal Phase 3 study, RYONCIL demonstrated clinically meaningful responses across the pediatric study population. The majority of patients (70%) achieved a response at Day 28, including those with severe SR-aGvHD.1-3

RYONCIL is the first and only FDA-approved SR-aGvHD treatment for pediatric patients 2 months of age and older, and the only approved treatment option for patients under 12 years of age.1,4

Explore the Evidence

High response rates in pediatric patients with high-grade disease1 

Demonstrated efficacy at Day 281

RYONCIL was studied in a multicenter, prospective, open-label, single-arm, Phase 3 trial of pediatric patients with SR-aGvHD Grade B to D (excluding Grade B skin alone),* following allogeneic hematopoietic stem cell transplantation (HSCT).1,2

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At Day 28, 70% of patients achieved a response, including those with the most severe SR-aGvHD1

Pediatric Response Chart
70%OVERALL RESPONSE
RATE (ORR)1

RYONCIL ORR (70%) compared with the prespecified null hypothesis of 45% (P=0.0003)1,2†

High ORR at Day 28 in patients with high-grade SR-aGvHD at baseline1

Median duration timeline

CI=confidence interval; CR=complete response; IBMTR=International Blood Marrow Transplant Registry; PR=partial response.
*Per the IBMTR Severity Index criteria.
†Calculated for two-sided exact binomial confidence interval at the 95% level. P value calculated from binomial distribution, assuming a 0.45 (45%) predefined control ORR under the null hypothesis.
Patients who died, withdrew from the study, or required second-line treatment before Day 28 were considered nonresponders.

Additional data from the clinical study 

Consistent results across clinical subgroups1-3

At Day 28, the majority of patients achieved a response, regardless of disease severity, organ involvement, or age group.1-3*

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Overall response at Day 28 by subgroup 

Results were generally consistent across prespecified subgroups.1-3* 

Disease severity

Disease severity

Grade of aGvHD at Baseline Day 28 ORR (%)
Grade B50% (n=3/6)
Grade C70% (n=16/23)
Grade D76% (n=19/25) 

Disease severity

Minnesota Risk Score Day 28 ORR (%)
Standard risk73% (n=11/15)
High risk69% (n=27/39)

Organ involvement

Organ involvement

Organ Involvement Day 28 ORR (%) 
Skin only 86% (n=12/14) 
Lower GI only 67% (n=14/21) 
Multiple organs63% (n=12/19)

Age

Age

Age Group Day 28 ORR (%)
0-7 years 71% (n=20/28)  
8-12 years 71% (n=10/14) 
13-17 years 67% (n=8/12) 

Organ involvement and disease severity were secondary endpoints.3

LIMITATIONS: These subgroup results are based on small sample sizes and could represent chance findings, and they were not adjusted for multiplicity; interpret with caution.

GI=gastrointestinal.

*N is based on the number of enrolled patients who received RYONCIL.

Specifically studied in pediatric patients1,2

Pivotal clinical study design 

RYONCIL was studied in a multicenter, prospective, open-label, single-arm, Phase 3 trial of pediatric patients with SR-aGvHD Grade B to D (excluding Grade B skin alone),* following allogeneic HSCT.1,2

  • SR-aGvHD was defined as progression within 3 days or no improvement within 7 days of steroid therapy (methylprednisolone 2 mg/kg/day or equivalent)1
  • A total of 55 patients were enrolled, and 54 were treated with RYONCIL. Patients received at least 1 infusion of RYONCIL via IV at a dose of 2 x 106 mesenchymal stromal cells/kg per infusion twice weekly for 4 consecutive weeks (up to 8 infusions)1,2
  • Patients with partial or mixed response at Day 28 could receive weekly infusions for 4 additional weeks; those with CR at Day 28 who experienced recurrence could restart twice-weekly dosing for 4 weeks1
Patients previously treated with second-line therapy were excluded from the study1
Primary endpoint1-3
  • Day 28 ORR rate (CR rate and PR rate)
Baseline characteristics1-3
AGE
AGE

Median age: 7 years

SEX
SEX

64% males; 36% females

Reason for HSCT
Reason for HSCT
  • 67% hematologic malignancy
  • 33% nonmalignant diseases
aGvHD GRADE
aGvHD GRADE
  • Grade B: 11% (excluded skin only)
  • Grade C: 43%
  • Grade D: 46%
Organ involvement 
Organ involvement 
  • Skin only: 26%
  • Lower GI only: 39%
  • Multiorgan: 35%
Race 
Race 
  • White: 56%
  • Other race: 19%
  • Black: 15%
  • Asian: 6%
  • American Indian or Alaska Native: 6%
  • Hispanic: 33%
  • Non-Hispanic: 65%
89 Percent 89% of patients had severe SR-aGvHD (Grade C or D) at baseline1

*Per the IBMTR Severity Index criteria.

Patient Profiles

Which patients are candidates for RYONCIL?

Explore a series of case-based patient profiles to see how RYONCIL is redefining what’s possible in pediatric SR-aGvHD.

View Patient Profiles
Review pediatric safety profile
Review pediatric safety profile

Examine the established pediatric safety profile.

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See how RYONCIL works 
See how RYONCIL works 

Learn more about cellular immunomodulation.

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References: 1. RYONCIL (remestemcel-L-rknd) package insert. New York, NY: Mesoblast, Inc; 09/2025. 2. Kurtzberg J, Abdel-Azim H, Carpenter P, et al; MSB-GVHD001/002 Study Group. A phase 3, single-arm, prospective study of remestemcel-L, ex vivo culture-expanded adult human mesenchymal stromal cells for the treatment of pediatric patients who failed to respond to steroid treatment for acute graft-versus-host disease. Biol Blood Marrow Transplant. 2020;26(5):845-854. 3. Data on file. Mesoblast Ltd. Clinical study report MSB-GVHD001. 4. US Food and Drug Administration. Summary Basis for Regulatory Action - RYONCIL. Published December 18, 2024. Accessed March 5, 2025. https://www.fda.gov/media/185192/download 

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INDICATION

RYONCIL is indicated for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGvHD) in pediatric patients 2 months of age and older.

Important Safety Information

Contraindications

Do not use RYONCIL in patients with known hypersensitivity to dimethyl sulfoxide (DMSO) or porcine and bovine proteins.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Acute Infusion Reactions

Hypersensitivity reactions including acute infusion reactions have occurred with RYONCIL administration. Serious hypersensitivity reactions, including anaphylaxis, may occur due to DMSO and trace amounts of porcine or bovine proteins. Signs and symptoms may include fever, dyspnea, and hypotension during or after RYONCIL infusion.

Premedicate patients with antihistamine and corticosteroids and monitor closely for signs and symptoms of hypersensitivity or acute infusion reactions.

If a hypersensitivity or infusion reaction occurs, interrupt RYONCIL infusion. Do not administer RYONCIL in patients who experience serious or life-threatening reactions.

Transmission of Infectious Agents

Transmission of infectious disease or agents may occur with RYONCIL administration because it contains cells from human donors and is manufactured using human, porcine and bovine-derived reagents. Donors are screened and tested for Human Immune-deficiency Virus 1 (HIV-1); Human Immune-deficiency Virus 2 (HIV-2); Hepatitis B Virus (HBV); Hepatitis C Virus (HCV); Human T-cell Leukemia-lymphoma Virus 1 (HTLV-1); Human T-cell Leukemia-lymphoma Virus 2 (HTLV-2); West Nile Virus (WNV); Cytomegalovirus (CMV); Epstein-Barr Virus (EBV); and Syphilis (Treponema pallidum). Screening was performed for Creutzfeldt-Jakob disease (CJD) and communicable disease risks associated with xenotransplantation. RYONCIL cell banks are tested for human and animal viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma. Human and animal-derived reagents are tested for human and animal viruses, bacteria, fungi, and mycoplasma before use. These measures do not eliminate the risk of transmitting these or other infectious diseases or agents.

Ectopic Tissue Formation

Ectopic tissue formation may occur following treatment with RYONCIL due to the ability of human mesenchymal stromal cells to differentiate into mesenchymal lineage cells such as bone, cartilage and fat cells.

ADVERSE REACTIONS

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The safety data described in this section reflect exposure to RYONCIL in 54 patients in Study MSB-GVHD001 for the treatment of SR-aGvHD. Patients received intravenous infusion of RYONCIL at a dosage of 2 x 106 MSCs/kg twice a week for four consecutive weeks, for a total of eight infusions. Patients with partial or mixed response at Day 28 received additional infusions of RYONCIL 2 x 106 MSCs/kg once a week for an additional four weeks. The median number of doses administered were 10 (range 1 to 16), and the treatment was administered over a median of 43 days (range 1 to 104 days).

Serious adverse reactions occurred in 35 patients (65%) including pyrexia (n=5;9%), respiratory failure (n=5;9%), pneumatosis intestinalis (n=4;7%) and staphylococcal bacteremia (n=2;<5%). 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).

Adverse reactions ≤ grade 3 occurring in ≥10% of patients in Study MSB-GVHD001 up to day 100 after RYONCIL treatment included viral infectious disorders, bacterial infectious disorders, infections – pathogen unspecified, pyrexia, hemorrhage, abdominal pain, hypertension, vomiting, arrhythmia, diarrhea, rash, arthralgia, fungal infectious disorders, hypotension, cough and respiratory failure. No grade 4 or 5 adverse reactions occurred in the study.

Grade 3 or 4 laboratory abnormalities that worsened from baseline in ≥ 10% of patients in Study MSB-GVHD001 included elevated Gamma-glutamyl transferase, thrombocytopenia, and elevated bilirubin.

USE IN SPECIFIC POPULATIONS

Pregnancy

There are no available data for RYONCIL use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with RYONCIL to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if RYONCIL has the potential to be transferred to the fetus. Therefore, RYONCIL is not recommended for women who are pregnant. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 10-20%, respectively.

Lactation

There is no information regarding the presence of RYONCIL in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RYONCIL and any potential adverse effects on the breastfed infant from RYONCIL or from the underlying maternal condition.

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.

INDICATION

RYONCIL is indicated for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGvHD) in pediatric patients 2 months of age and older.

Important Safety Information

Contraindications

Do not use RYONCIL in patients with known hypersensitivity to dimethyl sulfoxide (DMSO) or porcine and bovine proteins.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Acute Infusion Reactions

Hypersensitivity reactions including acute infusion reactions have occurred with RYONCIL administration. Serious hypersensitivity reactions, including anaphylaxis, may occur due to DMSO and trace amounts of porcine or bovine proteins. Signs and symptoms may include fever, dyspnea, and hypotension during or after RYONCIL infusion.

Premedicate patients with antihistamine and corticosteroids and monitor closely for signs and symptoms of hypersensitivity or acute infusion reactions.

If a hypersensitivity or infusion reaction occurs, interrupt RYONCIL infusion. Do not administer RYONCIL in patients who experience serious or life-threatening reactions.

Transmission of Infectious Agents

Transmission of infectious disease or agents may occur with RYONCIL administration because it contains cells from human donors and is manufactured using human, porcine and bovine-derived reagents. Donors are screened and tested for Human Immune-deficiency Virus 1 (HIV-1); Human Immune-deficiency Virus 2 (HIV-2); Hepatitis B Virus (HBV); Hepatitis C Virus (HCV); Human T-cell Leukemia-lymphoma Virus 1 (HTLV-1); Human T-cell Leukemia-lymphoma Virus 2 (HTLV-2); West Nile Virus (WNV); Cytomegalovirus (CMV); Epstein-Barr Virus (EBV); and Syphilis (Treponema pallidum). Screening was performed for Creutzfeldt-Jakob disease (CJD) and communicable disease risks associated with xenotransplantation. RYONCIL cell banks are tested for human and animal viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma. Human and animal-derived reagents are tested for human and animal viruses, bacteria, fungi, and mycoplasma before use. These measures do not eliminate the risk of transmitting these or other infectious diseases or agents.

Ectopic Tissue Formation

Ectopic tissue formation may occur following treatment with RYONCIL due to the ability of human mesenchymal stromal cells to differentiate into mesenchymal lineage cells such as bone, cartilage and fat cells.

ADVERSE REACTIONS

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The safety data described in this section reflect exposure to RYONCIL in 54 patients in Study MSB-GVHD001 for the treatment of SR-aGvHD. Patients received intravenous infusion of RYONCIL at a dosage of 2 x 106 MSCs/kg twice a week for four consecutive weeks, for a total of eight infusions. Patients with partial or mixed response at Day 28 received additional infusions of RYONCIL 2 x 106 MSCs/kg once a week for an additional four weeks. The median number of doses administered were 10 (range 1 to 16), and the treatment was administered over a median of 43 days (range 1 to 104 days).

Serious adverse reactions occurred in 35 patients (65%) including pyrexia (n=5;9%), respiratory failure (n=5;9%), pneumatosis intestinalis (n=4;7%) and staphylococcal bacteremia (n=2;<5%). 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).

Adverse reactions ≤ grade 3 occurring in ≥10% of patients in Study MSB-GVHD001 up to day 100 after RYONCIL treatment included viral infectious disorders, bacterial infectious disorders, infections – pathogen unspecified, pyrexia, hemorrhage, abdominal pain, hypertension, vomiting, arrhythmia, diarrhea, rash, arthralgia, fungal infectious disorders, hypotension, cough and respiratory failure. No grade 4 or 5 adverse reactions occurred in the study.

Grade 3 or 4 laboratory abnormalities that worsened from baseline in ≥ 10% of patients in Study MSB-GVHD001 included elevated Gamma-glutamyl transferase, thrombocytopenia, and elevated bilirubin.

USE IN SPECIFIC POPULATIONS

Pregnancy

There are no available data for RYONCIL use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with RYONCIL to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if RYONCIL has the potential to be transferred to the fetus. Therefore, RYONCIL is not recommended for women who are pregnant. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 10-20%, respectively.

Lactation

There is no information regarding the presence of RYONCIL in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RYONCIL and any potential adverse effects on the breastfed infant from RYONCIL or from the underlying maternal condition.

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.