Third time lucky for Mesoblast

After four years and two complete response letters, Mesoblast finally has FDA approval for its mesenchymal stem cell therapy Ryoncil (remestemcel-L) in paediatric steroid-refractory acute GvHD. The company, which first submitted a BLA in 2020, got the nod based on an uncontrolled phase 3 trial, MSB-GVHD001, which found a 70% ORR and 30% complete response rate at 28 days. Ryoncil’s cause was likely helped by the life-threatening nature of acute GvHD and the fact that, until now, there have been no US-approved therapies for children. Novartis/Incyte’s Jakafi has the nod for steroid-refractory disease, but in patients aged 12 and older; Jakafi recently received a positive CHMP opinion in children, but its US status is unclear. In Ryoncil’s first CRL the FDA asked for a randomised, controlled trial, as well questioning the potency assays designed to show consistency of the donor-derived product. Upon its second CRL Mesoblast proposed a study in adults who had failed steroids and Jakafi – a use also being targeted by MaaT Pharma. This trial is slated to start upon paediatric approval, and will be conducted by the Blood and Marrow Clinical Trials Network. Mesoblast, now facing a solo launch, had just $63m in cash as of Jun 2024. Ryoncil’s long road to FDA approvalEventTimingFDA approves Ryoncil for steroid-refractory acute GvHD in pts ≥2 months oldDec 2024Mesoblast says that following paediatric approval it will start a study in steroid and Jakafi-refractory adults; to be conducted by the Blood and Marrow Transplant Clinical Trials NetworkAug 2024FDA accepts Mesoblast’s BLA, setting PDUFA date of 7 Jan 2025Jul 2024FDA indicates that data from ph3 MSB-GVHD001 study appear sufficient to support a BLAMar 2024FDA issues second CRL; Mesoblast discloses plans to conduct study in adults with steroid-refractory acute GvHDAug 2023Mesoblast resubmits BLA, including long-term survival data & potency assay infoJan 2023FDA issues first CRL, recommending additional randomised, controlled study & requesting potency assay infoOct 2020FDA adcom votes 9-1 in favour of Ryoncil approvalAug 2020MSB-GVHD001 trial data published in Biology of Blood and Bone Marrow TransplantationMay 2020Mesoblast completes first rolling BLA submission for Ryoncil in paediatric steroid-refractory GvHD, based on single-arm ph3, MSB-GVHD001Jan 2020Source: OncologyPipeline.