FDA Grants Remestemcel-L Priority Review for Pediatric GVHD

The FDA has granted remestemcel-L a priority review designation for the treatment of children with steroid-refractory acute graft versus host disease.

The FDA has granted remestemcel-L (Ryoncil) a priority review designation for the treatment of children with steroid-refractory acute graft versus host disease (SR-aGVHD), according to Mesoblast Limited, the manufacturer of the allogeneic cell therapy.1

Under the Prescription Drug User Fee Act, the FDA is scheduled to decide on the application by September 30, 2020.

“There is a critical need to improve survival outcomes in children suffering from the more advanced stages of this devastating disease. The acceptance of the biologics license application represents an important milestone for the company. Mesoblast is on track in its preparation for the potential launch of Ryoncil, including meeting its target inventory build and commercial team roll-out,” Mesoblast Chief Executive Silviu Itescu, MBBS, FRACP, FACP, said in a press release.

According to Mesoblast, “Remestemcel-L is an investigational therapy comprising culture- expanded mesenchymal stem cells derived from the bone marrow of an unrelated donor. It is administered to patients in a series of intravenous infusions”

Study 275 explored remestemcel-L in 241 children with grade B to D SR-aGVHD enrolled at 50 sites in 8 countries.2 Most patients had grade C (30%) or grade D (50%) disease. The mean patient age was 9.6 years, 60% were white, and 39% were female. The patients did not respond to steroids with or without other secondary and tertiary immunosuppressive therapies.

Patients were administered 8 biweekly IV infusions of human mesenchymal stromal cells (2 × 106 per kg for 4 weeks) with an option for an additional 4 weekly infusions after day +28 for those patients who had either a partial response (PR) or a mixed response. The primary outcome measure was overall response rate (ORR) at day +28.

Among all patents, the 28-day ORR was 65.1% (n = 157), including a complete response rate of 14.1% (n = 34) and a PR rate of 51.3% (n = 123). The ORR at day +28 was 72.9%, 67.1%, and 60.8% for patients with a GVHD grade B, grade C, and grade D, respectively.

At day +100, overall survival (OS) was 66.9 % (160 of 239 evaluable patients). Of note, OS through day +100 was significantly higher among patients who had a day +28 OR compared with those who did not respond, at 82.1% versus 38.6%, respectively (P <.001).

The investigators considered remestemcel-L to be well tolerated, overall, with no safety issues.

In their conclusion, the authors wrote, “This update to the remestemcel-L expanded access program confirms the reported clinical and survival benefits of remestemcel-L therapy in children with aGVHD who have exhausted all conventional therapeutic options.”

According to Mesoblast, there are no treatments approved by the FDA for patients aged <12 years with SR-aGVHD.

Beyond GVHD, remestemcel-L is also being explored as a treatment for advanced heart failure and chronic low back pain.


  2. Kurtzberg J, Prockop S, Chaudhury S, et al. Study 275: updated expanded access program for remestemcel-L in steroid-refractory acute graft-versus-host disease in children [published online February 7, 2020]. Biol Blood Marrow Transplant. pii: S1083-8791(20)30059-8. doi: 10.1016/j.bbmt.2020.01.026