Stem-Cell Treatment for DDD Enters Phase 3

Denver docs have enrolled their first patient with back pain in the third phase of a landmark, nationwide study to test stem cell therapy for degenerative disc disease (DDD).

In Phase 2 patients were randomized to receive direct intra-disc injection of saline (n= 20), hyaluronic acid (HA, n=20), 6 million allogeneic mesenchymal precursor cells (MPCs) in hyaluronic acid carrier (6M, n=30) or 18 million allogeneic MPCs in hyaluronic acid carrier (18M, n=30) for a single painful degenerated lumbar level.

Patients in this trial are being followed for a total of 36 months to evaluate long-term efficacy and safety.

And here is how the patients did after one year:

• Statistically significant chronic low back pain relief
  • Reduction in mean pain score: While mean pain scores, as measured by a Visual Analog Scale (VAS), were similar for all four groups at baseline (67 points for saline, 72 points for HA, 70 points for 6M MPC, 72 points for 18M MPC), at 12 months MPC treatment resulted in significantly greater pain reduction than was seen in controls. Mean pain reduction at 12 months was 40 points for the 18M MPC group, 37 points for the 6M MPC group, 27 points for HA controls, and 27 points for saline controls (p=0.046 and p=0.11, respectively, for 18M MPC and 6M MPC vs pooled controls).
  • Increased proportion of patients achieving >50% reduction in pain score: Achieving more than 50% reduction in low back pain at 12 months is considered by many patients and physicians as a key target. A significantly greater proportion of MPC treated patients achieved at least a 50% reduction in low back pain at 12 months, as measured by VAS, than controls (6M MPC 69%, 18M MPC 62%, HA 35%, saline 31%, p=0.036 between groups). Both MPC dose groups had a significantly greater proportion of patients with 50% or more reduction in back pain from baseline compared to the pooled controls (6M, p=0.009, 18M p=0.038).
  • Increased proportion of patients achieving minimal residual back pain: Minimal residual back pain at 12 months was considered if the VAS score was <20. A significantly greater proportion of MPC treated patients achieved minimal residual back pain at 12 months than controls (6M group 52%, 18M group 42%, pooled controls 18%, p=0.01 and p=0.05, respectively).
  • Reduced opioid use for pain relief: At 12 months, mean daily use of opioid medications for back pain was reduced by as much as 42% in the 18M MPC group compared with the saline control group (p=0.17). Mean opioid use was 1.00 tablet/day saline group, 0.94 tablet/day HA group, 0.77 tablet/day 6M MPC group, and 0.58 tablet/day 18 MPC group. Mean opioid use was also over two-fold higher in saline and HA controls achieving >50% reduction in pain score than in MPC treated patients, indicating that pain reduction in the controls may have been due to high opioid intake rather than to any biologic effect (mean opioid use 1.3 and 1.2 tablets/day in saline and HA controls compared with 0.7 and 0.6 tablets/day for the 6M and 18M MPC groups).
  • Reduced need for additional surgical and non-surgical interventions for persistent pain: MPC-treated patients had a significantly reduced need for additional interventions at the treated disc level, including surgical intervention (spine fusion, discectomy or artificial disc replacement) or injection (epidural steroid injection, rhizotomy or transforaminal injections), than saline controls. By 12 months, 25% saline controls had undergone an additional intervention, compared with 10% HA controls, 6.9% of 6M MPC and only 3.3% of 18M MPC treated patients. By Kaplan-Meier analysis of time to a first additional treatment intervention, treatment with either 6M or 18M MPC significantly reduced the need for additional interventions compared with saline treatment (p=0.024 and p=0.010, respectively).
• Improvement in function
  • Reduction in mean disability score: At 12 months, MPC treatment resulted in greater improvement in function than was seen in controls, as measured by the Oswestry Disability Index (ODI). Mean reduction in the ODI functional disability score was 43% for the 18M MPC group, 35% for the 6M MPC group, 30% for HA controls, and 28% for saline controls (p=0.09 for 18M MPC group vs saline).
  • Increased proportion of patients achieving minimal residual functional disability: Minimal residual functional disability at 12 months was considered if the ODI score was <20. A greater proportion of MPC treated patients achieved minimal residual functional disability at 12 months than controls (18M group 39%, 6M group 36%, pooled controls 18%, p=0.14 and p=0.14, respectively).
• Improvement in disc stability
  • In patients with early disc degeneration (Pfirrmann MRI degenerative grades below 5), increased translational movement of the disc is a potential indicator of instability associated with early disc degeneration and annular fissures seen on MRI and pathologic examination. At 12 months, MPC-treated patients demonstrated a significant reduction in radiographically-determined translational movement of the disc, suggesting a treatment effect on disc degeneration, anatomy, and improved disc stability. The 18M MPC group had a mean translational movement of only 1.3%, the 6M MPC group 2%, the HA group 2.5%, and the saline group 3.5% (p=0.021 between groups). When adjusting translation per degree of rotation (TPDR), a similar treatment effect on reduced translational movement was seen in both the 6M and 18M MPC groups.

Now Comes Phase 3

The FDA cleared study has now started the third and final phase of its testing for FDA approval and eventual commercialization.

Degenerative disc disease is the most common cause of low-back pain experienced by an estimated 10 million in the United States. In many cases, the cause of the back pain is the loss of a material called proteoglycan which cushions the bones of the spine.
J. Scott Bainbridge, M.D., of Denver Back Pain Specialists is leading the team of researchers. “The clinical program is the first of its kind in the United States and we are very excited by the potential of these adult stem cells to provide a novel therapeutic approach, ” Bainbridge said.

The Phase 3 study will enroll approximately 330 study participants at the Denver site and at multiple other medical centers throughout the United States. Patients will be followed for 12 months post-treatment.

Once enrolled, patients will be randomly assigned to one of three treatment groups. One-third will receive a 6 million cell dose of MPCs, plus hyaluronic acid, a substance that facilitates the localization and retention of stem cells. The second third will receive a 6 million cell dose of MPCs alone; and the final third will receive only an injection of saline solution.

Bainbridge participated in the preceding Phase 2 clinical trial, which found that the cells were well tolerated. The 6 million cell dose resulted in a greater proportion of patients achieving reduced back pain compared to patients who had not received the cells. This study is sponsored by Mesoblast Limited, a leader in cell-based regenerative medicine.