Phase 3 Data Garners RMAT Designation for Chronic Low Back Pain Cell Therapy

Mesoblast’s rexlemestrocel-L, an investigational allogeneic human bone marrow-derived mesenchymal precursor cell (MPC) therapy, has received regenerative medicine advanced therapy (RMAT) designation from the FDA’s Office of Tissues and Advanced Therapies for the treatment of chronic low back pain (CLBP) associated with disc degeneration in combination with hyaluronic acid (HA).

Rexlemestrocel-L was recently evaluated in a phase 3 clinical trial (NCT02412735; MSB-DR003). The 404 participants in the trial were treated with either rexlemestrocel-L in combination with HA, rexlemestrocel-L alone, or a saline control. Rexlemestrocel-L was administered via a 2.0 mL injection into the lumbar disc consisting of approximately 6x10⁶ cells in freeze media mixed in a 1:1 volume ratio with either HA or saline, depending on the patient’s randomly assigned cohort.

At 12 months and 24 months post-treatment, significant reductions in pain were reported for participants who received rexlemestrocel-L+HA in comparison to patients who received the saline control. It was noted that a pre-specified group of 194 participants with shorter duration CLBP than the study’s median duration of 68 months achieved a substantially enhanced reduction in low back pain. Furthermore, significant improvements in assessments of function and quality of life were demonstrated in patients with a shorter duration of CLBP. Among the 168 participants using opioids at baseline, pain reduction was observed through 36 months, with the patients in this group who received rexlemestrocel-L+HA showing substantially greater pain reduction at all time points in comparison to the patients in this group who receive the saline control. It was additionally noted that 28% of the participants who were using opioids at baseline and received rexlemestrocel-L+HA had ceased opioid use at the 36 month mark, despite instructions to continue using baseline therapies for the duration of the trial. In contrast, 8% of participants who were using opioids at baseline and received the saline control had ceased opioid use at 36 months.

“We are pleased to receive RMAT designation for our cellular therapy to treat CLBP due to disc degeneration” SilviuItescu, chief executive, Mesoblast, said in a statement regarding the news.¹ “We look forward to working closely with FDA to efficiently generate the additional data needed to support marketing approval of rexlemestrocel-L for the treatment of this serious and debilitating condition.”

In addition to CLBP, rexlemestrocel-L was also evaluated for the treatment of chronic heart failure in a phase 3 clinical trial (NCT02032004; DREAM HF-1) that was completed in May 2020. Mesoblast is also developing remestemcel-L, a mesenchymal stromal cell therapy, for indications including steroid-refractory acute graft versus host disease (SR-aGVHD), biologic-resistant inflammatory bowel disease, and acute respiratory distress syndrome.² In February 2023, the company resubmitted a biologics license application (BLA) for remestemcel-L for the treatment of pediatric patients with SR-aGVHD, 4 years after it had originally initiated a rolling BLA for the therapy. Remestemcel-L is being evaluated in 2 phase 1b/2a clinical trials for the treatment of refractory ulcerative (NCT04543994) and Crohn colitis (NCT04548583), respectively.

REFERENCES

1. FDA grants regenerative medicine advanced therapy (RMAT) designation for rexlemestrocel-L in chronic low back pain. News release. Mesoblast Limited. February 8, 2023. Accessed February 10, 2023.https://investorsmedia.mesoblast.com/static-files/ca23828a-c4a2-42b1-8865-6a437277e472 

2. Mesoblast resubmits biologic license application (BLA) to FDA for Remestemcel-L in children with steroid-refractory acute graft versus host disease (Sr-aGVHD). News release. Mesoblast. February 1, 2023. https://www.globenewswire.com/news-release/2023/01/31/2599031/0/en/Mesoblast-Resubmits-Biologic-License-Application-BLA-to-FDA-for-Remestemcel-L-in-Children-With-Steroid-Refractory-Acute-Graft-Versus-Host-Disease-Sr-aGVHD.html