Expert Clinical Network Insights: March 2025 - Prime Therapeutics
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Steroid-refractory acute graft-versus-host disease
March 18, 2025
Medication insights: remestemcel-L-rknd (Ryoncil)
The U.S. Food and Drug Administration (FDA) approved remestemcel-L-rknd (Ryoncil) in December 2024 for the treatment of steroid-refractory (SR)-acute graft-versus-host disease (aGvHD) in pediatric patients 2 months of age and older.¹˒² Prime Therapeutics sought insight from key opinion leader(s) (KOLs) within our Expert Clinical Network (ECN) who specialize in hematology and oncology. This month’s newsletter summarizes KOL feedback on this first FDA-approved mesenchymal stromal cell (MSC) therapy for SR-aGvHD.¹
Efficacy
Ryoncil is comprised of allogeneic bone marrow-derived MSCs. It is thought to elicit its therapeutic effect by modulating the immune system. MSCs have properties that can suppress excessive inflammation and regulate immune responses. These characteristics are beneficial in conditions such as graft-versus-host disease (GvHD), in which immune dysfunction is the target.
The efficacy of Ryoncil was assessed in a single-arm, Phase 3 trial of pediatric patients with SR-aGvHD. In this trial, 54 children with primary SR-aGvHD who were naïve to other immunosuppressant treatments were treated with intravenous (IV) Ryoncil twice weekly for four weeks. The primary endpoint was the ORR, which was defined as the percentage of patients showing complete response (CR) or partial response (PR) to their treatment. The ORR at day 28 was 70.4% as compared to 45% for the prespecified control group, which was clinically significant. This ORR was sustained through day 100 and included an increasing rate of CR from 29.6% at day 28 to 44.4% at day 100. The most notable metric of improvement was the overall survival (OS) rate of 74.1% at day 100 and 68.5% at day 180. Additionally, survival was greater in responders compared to nonresponders at day 100 (86.8% versus 47.1%, respectively).³
In a separate Phase 3 trial that included both adults and pediatric patients, Ryoncil did not meet the primary endpoint of greater durable complete response (DCR) in the intent-to-treat population (35% for Ryoncil versus 30% for placebo). However, a post hoc analysis of this study showed that patients with liver involvement had a statistically significant higher DCR when treated with Ryoncil as compared to placebo (29% versus 5%, respectively; P = 0.047). Additionally, high-risk patients with aGvHD grade C or grade D demonstrated higher overall responses in patients treated with Ryoncil versus placebo at day 28 (58% versus 37%, respectively; P = 0.03). When looking at the pediatric patients in this study, there was a higher ORR in this patient population treated with Ryoncil as compared to placebo (64% versus 23%, respectively; P = 0.05).⁴
The efficacy of Ryoncil was assessed in a single-arm, Phase 3 trial of pediatric patients with SR-aGvHD. In this trial, 54 children with primary SR-aGvHD who were naïve to other immunosuppressant treatments were treated with intravenous (IV) Ryoncil twice weekly for four weeks. The primary endpoint was the ORR, which was defined as the percentage of patients showing complete response (CR) or partial response (PR) to their treatment. The ORR at day 28 was 70.4% as compared to 45% for the prespecified control group, which was clinically significant. This ORR was sustained through day 100 and included an increasing rate of CR from 29.6% at day 28 to 44.4% at day 100. The most notable metric of improvement was the overall survival (OS) rate of 74.1% at day 100 and 68.5% at day 180. Additionally, survival was greater in responders compared to nonresponders at day 100 (86.8% versus 47.1%, respectively).³
In a separate Phase 3 trial that included both adults and pediatric patients, Ryoncil did not meet the primary endpoint of greater durable complete response (DCR) in the intent-to-treat population (35% for Ryoncil versus 30% for placebo). However, a post hoc analysis of this study showed that patients with liver involvement had a statistically significant higher DCR when treated with Ryoncil as compared to placebo (29% versus 5%, respectively; P = 0.047). Additionally, high-risk patients with aGvHD grade C or grade D demonstrated higher overall responses in patients treated with Ryoncil versus placebo at day 28 (58% versus 37%, respectively; P = 0.03). When looking at the pediatric patients in this study, there was a higher ORR in this patient population treated with Ryoncil as compared to placebo (64% versus 23%, respectively; P = 0.05).⁴
Safety and patient experience
Across the Ryoncil trials, its safety profile was consistent. Ryoncil appears to be very well-tolerated with no remarkable treatment-related adverse events (trAEs). Notably, in a trial that investigated its use versus placebo in both adults and children, Ryoncil had a lower rate of probable trAEs compared with placebo (1.2% versus 3.7%, respectively).⁴ This data is a good indicator that Ryoncil is well-tolerated. Similarly, infusion-related reactions were reported in 1.8% of patients receiving Ryoncil as compared to 2.5% of patients receiving placebo. A trend toward higher rate of deaths associated with infections was seen in the Ryoncil group as compared to placebo (26% versus 15%, respectively; P = 0.07); however, the overall rates of infection were similar between the two groups (88% for Ryoncil versus 82% for placebo). TrAEs occurred at similar rates between the Ryoncil and placebo groups.⁴
Of note, the Ryoncil prescribing information includes recommendations for treatment based on day 28 response; select patients may receive additional treatment with Ryoncil. For patients achieving a partial or mixed response, the prescribing information recommends repeat administration of Ryoncil once a week for an additional four weeks. In patients who have a recurrence of GvHD after a CR, it is then recommended to repeat administration of Ryoncil twice a week for an additional four consecutive weeks.² In the Phase 3 single-arm study, 30 of 54 patients received more than the initial eight infusions of Ryoncil (25 patients for continued therapy and five patients for aGvHD flare [9 to 16 infusions]).³ It is estimated that approximately two-thirds of patients may need additional infusions of Ryoncil.
Of note, the Ryoncil prescribing information includes recommendations for treatment based on day 28 response; select patients may receive additional treatment with Ryoncil. For patients achieving a partial or mixed response, the prescribing information recommends repeat administration of Ryoncil once a week for an additional four weeks. In patients who have a recurrence of GvHD after a CR, it is then recommended to repeat administration of Ryoncil twice a week for an additional four consecutive weeks.² In the Phase 3 single-arm study, 30 of 54 patients received more than the initial eight infusions of Ryoncil (25 patients for continued therapy and five patients for aGvHD flare [9 to 16 infusions]).³ It is estimated that approximately two-thirds of patients may need additional infusions of Ryoncil.
Want more information on this topic and more from our KOLs?
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Our Expert Clinical Network is part of our value-based approach to medical and pharmacy benefit management where customers have access to over 175 national and world-renowned key opinion leaders in multiple disease categories. These experts assist clients with challenging prior authorization case reviews, peer-to-peer discussions, drug policy development and formulary guidance. Our ECN supports health plans and providers to make more informed decisions, leading to positive patient outcomes and avoidance of inappropriate care.
The information contained in this report is intended for educational purposes only and is not intended to define a standard of care or exclusive course of treatment, nor be a substitute for treatment. All brand names are property of their respective owners.
References
The information contained in this report is intended for educational purposes only and is not intended to define a standard of care or exclusive course of treatment, nor be a substitute for treatment. All brand names are property of their respective owners.
References
- FDA approves first Mesenchymal stromal cell therapy to treat steriod-refractory acute graft-versus-host disease. Accessed January 27, 2025. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host .
- Ryoncil. Package insert. New York, NY: Mesoblast, Inc; December 2024.
- Kurtzberg J, Abdel-Azim H, Carpenter P, et al. 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. DOI:10.1016/j.bbmt.2020.01.018.
- Kebriaei P, Hayes J, Daly A, et al. A phase 3 randomized study of remestemcel-L versus placebo added to second-line therapy in patients with steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2020;26(5):835-844. DOI:10.1016/j.bbmt.2019.08.029.
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