Mesoblast Phase 3 Trial Shows That a Single Injection of Rexlemestrocel-L + Hyaluronic Acid Carrier Results in at Least Two Years of Pain Reduction With Opioid Sparing Activity in Patients With Chronic Low Back Pain Due to Degenerative Disc Disease
NEW YORK, Feb. 10, 2021 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced results from the Phase 3 randomized controlled trial of its allogeneic mesenchymal precursor cell (MPC) therapy rexlemestrocel-L in 404 enrolled 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 for patients with chronic inflammatory back pain due to degenerative disc disease, and that greatest benefits are seen when administered earlier in the disease process before irreversible fibrosis of the intervertebral disc has occurred.
“The durable pain reduction for at least two years from a single administration indicates that rexlemestrocel-L has the potential to change the treatment paradigm for chronic low back pain due to inflammatory disc disease, a condition that affects as many as seven million patients across the United States and Europe, and to prevent or reduce opioid use and dependence,” said Dr. Silviu Itescu, Chief Executive Officer of Mesoblast.
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 study was conducted across 48 sites, predominantly in the United States. In a previous randomized controlled trial in patients with refractory CLBP, up to 80% of whom were taking opioids, a single injection of 6 million MPC + HA carrier significantly reduced CLBP for at least two years, while HA alone was no different than saline.1
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. Key analyses were performed on the total study population and on the pre-specified subsets of opioid users at baseline and patients with CLBP duration shorter or longer than the median for the whole study population.
Regulatory approval of pharmaceutical agents, such as opioids, in the treatment of chronic pain syndromes generally requires reduction in pain as the primary outcome. In the midst of the opioid epidemic in the United States, the Food and Drug Administration has prioritized a focus on new therapeutics that target both pain reduction and opioid avoidance2, particularly for treating CLBP which accounts for 50% of opioid prescriptions.3-5 In addition to assessing the durability of pain reduction with rexlemestrocel-L treatment, this study evaluated primary outcomes using composite measures of pain reduction together with functional responses to treatment, as well as exploratory composites of pain reduction and functional responses in the context of opioid reduction.
A single injection of MPC + Hyaluronic Acid (HA) carrier resulted in:
Importantly, in patients using opioids at baseline, the results showed:
Mesoblast will meet with the FDA to discuss the results from this trial together with the earlier randomized controlled trial of MPC + HA, and potential approval pathways for rexlemestrocel-L + HA as treatment for durable reduction in CLBP due to DDD with opioid sparing activity.
Entire Treated Population of Patients
Figure 1: LS Mean VAS Low Back Pain Change from Baseline VAS of 60.4 – Entire Study (n=391)
Maximal pain reduction with MPC + HA was seen in the pre-specifiedsubset of patients treated within a shorter duration of CLBP than the study’s median of 68 months (n=194). Figure 2 shows the least-squared (LS) mean change from baseline in patients treated with MPC + HA was -36.9 at 12 months and -36.5 at 24 months (p<0.0001 at both timepoints compared with saline-treated controls). Further, minimal to no pain (VAS < 20) was seen in 60% of these patients treated with MPC + HA at 12 months and in 54% at 24 months (p=0.011 and p=0.036, respectively, compared to saline controls).
Figure 2: LS Mean VAS Low Back Pain Change from Baseline - Duration CLBP < Median (n=194)
Pre-specified measurements of function and disability showed that the EuroQoL 5-dimensional questionnaire (EQ-5D) Index appeared to be a more sensitive discriminator of treatment effect than the Oswestry Disability Index (ODI) in this patient population. In the population with shorter duration of CLBP than the median for the study, MPC + HA improved function and disability compared with saline at both 12 and 24 months, as measured by either EQ-5D Index (p=0.009 and p=0.020, respectively) or ODI (p=0.044 and p=0.059, respectively). In these patients MPC + HA resulted in increased composite responder outcomes at 24 months of 50% reduction in pain and improvement in function as measured by either >0.03 EQ-5D Index or by >15-point ODI (p=0.04 and p=0.06, respectively).
Population of Patients Taking Opioids
In the pre-specified population of opioid users at baseline (n=168), patients who received a single injection of MPC + HA had a significantly greater reduction in pain at all time-points (1, 3, 6, 12, 18 and 24 months) compared with saline controls (p<0.05 for all timepoints). Importantly, despite instructions to treating physicians and patients to not change any medications during the trial, by 24 months there was a 40% reduction in opioid use (as measured by morphine equivalent dose, MED) in patients treated with a single injection of MPC + HA (p=0.03). Conversely, more saline treated opioid users actually increased their daily MED opioid use over 24 months than those treated with MPC + HA (50% vs 13% at 24 months, p=0.0009).
By 24 months, 46% of patients treated with MPC + HA achieved 50% reduction in VAS together with opioid MED dose reduction compared with only 12% of saline controls (p=0.004), and 32% vs 12% (p=0.05) achieved a composite of 50% reduction in VAS and 15-point improvement in ODI together with opioid reduction. Treatment with MPC + HA resulted in a 5-fold increase in the proportion of patients achieving a composite of 50% reduction in pain and an EQ-5D Index response at both 12 and 24 months (33% vs 6%, p=0.006) while at the same time reducing opioid use.
Mesoblast Chief Medical Officer Dr. Fred Grossman said: “These results show very meaningful improvements in debilitating CLBP for at least two years after a single injection of our anti-inflammatory mesenchymal precursor cells (MPCs) in an outpatient procedure. On the basis of the Phase 3 trial results, we intend to meet with the FDA and discuss potential pathways towards approval for rexlemestrocel-L, including as an opioid sparing treatment in patients with DDD.”
About Chronic Low Back Pain due to Degenerative Disc Disease
Back pain causes more disability than any other condition9 and inflicts substantial direct and indirect costs on the healthcare system9, 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).10 More than 50% of US opioid prescriptions are for the treatment of CLBP,3-5 despite the fact that opioids are associated with serious and potentially life-threatening side effects and have not demonstrated efficacy in the treatment of CLBP.5,11,12 In 2018, more than 67,000 drug overdose deaths occurred in the United States13 of which almost 47,000 (70%) were opioid related.
Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2040 in all major markets. The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.
Mesoblast has completed Phase 3 trials of rexlemestrocel-L for advanced chronic heart failure and chronic low back pain. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease and moderate to severe acute respiratory distress syndrome. Two products have been commercialized in Japan and Europe by Mesoblast’s licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.
Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast
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