Mesoblast announced results from a Phase 3 trial of its allogeneic mesenchymal precursor cell (MPC) therapy rexlemestrocel-L in patients with chronic low back pain (CLBP) due to degenerative disc disease (DDD) refractory to conventional treatments. The results indicate that a single injection of rexlemestrocel-L may provide a safe, durable, and effective opioid sparing therapy.
The prospective, multicenter, randomized, double-blind, placebo-controlled study was designed to evaluate the safety and efficacy of Mesoblast’s rexlemestrocel-L alone or combined with hyaluronic acid (HA) in subjects (n=404) with chronic low back pain (> 6 months) associated with moderate radiographic degenerative changes of a disc. Patients were randomized 1:1:1 to receive a single intra-discal injection of either rexlemestrocel-L using a unit dose of 6 million allogeneic mesenchymal precursor cells (MPCs), with or without hyaluronic acid (HA) carrier, or saline control, and stratified for opioid use at baseline to ensure all three treatment arms were equally represented in this pre-defined population. The effectiveness of rexlemestrocel-L alone or rexlemestrocel-L + HA through 24 months was evaluated on reduction in pain using Visual Analog Score (VAS) and on disability or function using two measurements, Oswestry Disability Index (ODI) and EuroQoL 5-Dimensional (EQ-5D) Index.
A single injection of MPC + HA carrier resulted in significant and durable reductions in CLBP through 24 months across the entire evaluable study population (n=391) compared with saline controls. The greatest pain reduction was observed in the pre-specified population with CLBP of shorter duration than the study median of 68 months (n=194), with a significantly greater reduction at all time points (1, 3, 6, 12, 18 and 24 months) compared with saline controls. Significantly greater pain reduction was observed in the pre-specified patient subset of opioid users (n=168) at all time-points compared with saline controls. No safety concerns over the 24-month period of follow-up in the entire study population
In patients using opioids at baseline, the results showed a significant reduction in opioid use over 24 months in patients treated with MPC + HA, while increased opioid use occurred in saline controls. In addition, treatment with MPC + HA resulted in nearly four times more opioid users achieving 50% reduction in pain as well as reduction in opioid use by 24 months than those treated with saline.
Mesoblast plans to present these findings to the FDA and discuss potential pathways towards approval for rexlemestrocel-L, including as an opioid sparing treatment in patients with DDD.
Rexlemestrocel-L consists of a unit dose of 6 million mesenchymal precursor cells (MPCs). It is injected by syringe directly into a targeted damaged disc in an outpatient procedure. Extensive preclinical studies have established that MPCs have anti-inflammatory effects and secrete multiple paracrine factors that stimulate new proteoglycan and collagen synthesis by chondrocytes in vitro and by resident cells in the nucleus and annulus in vivo. MPCs have also been shown to produce anti-inflammation factors. Together these effects offer the potential to strengthen the load bearing function of the disc by increasing its water content, improving disc anatomy and stability, while also reducing inflammation and pain.
About Chronic Low Back Pain due to Degenerative Disc Disease
Chronic low back pain (CLBP) affects approximately 10-15% of the adult population. Degenerative disc disease (DDD) causing discogenic pain is the most common etiology of CLBP in adults. Over 7 million patients in each of the United States and E.U. are thought to suffer from CLBP caused by degenerative disc disease, a disease which involves inflammation and degeneration of the intervertebral discs due to various factors including age, trauma or genetic pre-disposition. Back pain causes more disability than any other condition and inflicts substantial direct and indirect costs on the healthcare system, including excessive use of opioids in this patient population. There are few treatment options for patients with CLBP who fail conservative therapy, including opioids, spinal injections and surgery (e.g., spinal fusion or total disk arthroplasty). More than 50% of US opioid prescriptions are for the treatment of CLBP, even though opioids are associated with serious and potentially life-threatening side effects and have not demonstrated efficacy in the treatment of CLBP.