The resubmitted biologics license application for remestemcel-L has been issued a complete response letter.
The FDA has issued a complete response letter to the biologics license application (BLA) resubmission for remestemcel-L (Ryoncil), which states that more data are needed to support the approval of this drug for pediatric patients with steroid-refractory acute graft-vs-host disease (aGVHD).1
Additional data will be collected through a targeted, controlled study in adult patients with the highest risk and greatest mortality.
“[The] FDA’s inspection of our manufacturing process resulted in no observed concerns, the Agency raised no safety issues across more than 1300 patients who have received remestemcel-L to date, and acknowledged improvements to our potency assay,” Silviu Itescu, chief executive at Mesoblast, said in a news release. “We remain steadfast in making remestemcel-L available to both children and adults suffering from this devastating disease and have received substantial clarity in how to bring this much-needed product to these patients.”
Pilot data compiled through the company’s emergency investigational new drug program in adults demonstrated a survival benefit with remestemcel-L in the target population for the trial. The company is now working with investigators across the United States to plan the adult follow-on study protocol and will meet with the FDA within 45 days to discuss the trial design in a Type A meeting.
Prior to the resubmission, per FDA guidance, Mesoblast corrected outstanding chemistry, manufacturing, and controls issues before launching another trial. The regulatory agency completed the pre-license inspection of the manufacturing facility, did not issue any Form 483, and found no objectionable conditions. Moreover, in the resubmission review the FDA stated that the changes made to the assay seemed to improve its performance for subsequent research.
Previously, the prespecified primary end point of a single-arm phase 3 trial in 54 children with steroid-refractory aGVHD was met, and the company agreed with the FDA to the terms of the trial. In August 2020, the FDA’s Oncologic Drugs Advisory Committee voted 9:1 in favor of remestemcel-L’s efficacy in a pediatric patient population. However, in September 2020, the FDA recommended that additional steps be taken to receive approval.
The BLA, which was resubmitted in January 2023 and accepted for review in March 2023,2 included long-term follow-up data from the phase 3 trial led through the Center for International Blood and Marrow Transplant Research. These data showed that half of patients remained alive after more than 4 years of follow-up. The resubmission also included a post-hoc propensity matched study showing a 6-month survival rate of 67% with remestemcel-L vs 10% with other unapproved therapies in highest-risk patients defined by the Mount Sinai Acute GVHD International Consortium.
“These pediatric data provide further support for use of remestemcel-L in the proposed study in high-risk adults with steroid-refractory, acute GVHD,” Mesoblast stated in the press release.