DiscGenics, Inc., a privately held, late-stage clinical, biopharmaceutical company developing allogeneic, cell-based, regenerative therapies for musculoskeletal degeneration, announced publication of results in the International Journal of Spine Surgery from the combined Phase I/Phase II, first-in-human clinical study of an allogeneic disc progenitor cell therapy (IDCT or rebonuputemcel) for painful lumbar degenerative disc disease (DDD).
The study met the primary safety and efficacy endpoints, showing that a single intradiscal injection of high-dose IDCT (9,000,000 cells/mL) safely increases disc volume and produces statistically significant, clinically meaningful improvements in back pain, disability, and quality of life out to 2 years post-injection in patients with lumbar disc degeneration.
"The results from this study demonstrate IDCT's potential to safely and effectively reduce pain associated with DDD while also producing a regenerative effect within the degenerating disc. MRI image analysis of disc volume indicated the potential to halt and possibly reverse the progression of the disease," said Matthew F. Gornet, M.D., lead author, Board Certified Spine Surgeon at The Orthopedic Center of St. Louis, and top enroller in the IDCT study. "I have been a practicing spine surgeon for more than 30 years and been involved in over 35 FDA clinical trials, and the patient outcomes from this study are very promising."
In the FDA-allowed, prospective, randomized, double-blinded, vehicle- and placebo-controlled, multicenter study, 60 patients with symptomatic, single-level lumbar DDD were randomized to receive single intradiscal injections of either low-dose cells (n = 20), high-dose cells (n = 20), vehicle alone (n = 10), or placebo (n = 10). The primary endpoint was mean visual analog scale (VAS) pain improvement >30% at 52 weeks. Disability and quality of life were evaluated via Oswestry Disability Index (ODI) and EQ-5D, respectively. Disc volume was radiologically assessed. Adverse events (AEs), regardless of whether they were related to treatment, were reported. Patients were assessed at baseline and at 4, 12, 26, 52, 78, and 104 weeks post treatment.
At Week 52, the primary study period, the high-dose group had a mean VAS percentage decrease from baseline (−62.8%, P = 0.0005), achieving the endpoint of back pain improvement >30%; the mean change was also significantly greater than the minimal clinically important difference (MCID) of a 20-point decrease (−42.8, P = 0.001). This clinical improvement was maintained at Week 104.
In addition, the high-dose group had clinically meaningful, statistically significant improvements in ODI and EQ-5D by 12 weeks. Clinical improvement was sustained at 26 weeks, 52 weeks, 78 weeks, and 104 weeks following a single intradiscal injection. Only the high-dose group had a significant change in disc volume, with mean increases of 249.0 mm3 (P = 0.028) at 52 weeks and 402.1 mm3 (P = 0.028) at 104 weeks. Overall, a minority of patients (18.3%) reported AEs that were severe, with the highest percentage being reported in the placebo group. During the course of the trial, 6.7% of patients experienced serious AEs, all occurring in the vehicle (n = 1) or placebo (n = 3) groups, none were treatment related.
"Since the inception of DiscGenics, we have seen consistent evidence of safety and the regenerative potential of the unique disc cell population in IDCT to address disc degeneration," said Kevin T. Foley, MD, Chief Medical Officer of DiscGenics and Chairman of Semmes-Murphey Neurologic & Spine Institute. "Our early basic science studies, our demonstrated ability to safely use human cells in 14 different pre-clinical animal studies conducted in the U.S. and Japan, and recently, data from our first-in-human safety and patient-reported outcomes published in this IJSS manuscript, all support the notion that this cell has the potential to safely regenerate the intervertebral disc from the inside-out."
DDD is a chronic and progressive condition where the intervertebral disc breaks down and causes pain and disability. It accounts for nearly 40% of chronic low back pain cases in the U.S., a serious medical condition that affects 12-30% of U.S. adults at a given time and is estimated to cost the U.S. healthcare system over $100 billion each year, creating a considerable burden on the economy and individual patients.
"The significant and durable results from this study demonstrate the incredible potential of IDCT to change the paradigm of care for patients with DDD, a condition with limited treatment options," said Flagg Flanagan, Chief Executive Officer and Chairman of the Board for DiscGenics." We are excited by the momentum the publication of these study results offers, as we expect to initiate Phase III clinical study of this novel therapy in the U.S. imminently."
About IDCT:
IDCT (injectable disc cell therapy, or rebonuputemcel) is a standalone, single-injection biologic treatment designed to halt progression of symptomatic lumbar disc degeneration and regenerate the disc from the inside out. The active ingredient (Drug Substance) in IDCT is a live, manufactured progenitor cell population derived from donated adult human intervertebral disc tissue. These cells are enriched and expanded into Discogenic Cells through a multistep manufacturing process in a highly controlled environment under current good manufacturing practices (cGMP) that results in significant proliferation and phenotypic changes to the cells. At the completion of the manufacturing process, the Discogenic Cells are subjected to extensive testing prior to use, including identity, purity, potency, and safety evaluations. The Discogenic Cells are then mixed with a viscous Sodium Hyaluronate Solution and excipients to generate IDCT, the Final Drug Product. IDCT is cryopreserved and maintained as individual "off-the-shelf" doses for administration via percutaneous injection into the intervertebral disc in an outpatient setting. IDCT has been granted regenerative medicine advanced therapy (RMAT) and Fast Track designations by the U.S. Food and Drug Administration.
For more information, visit www.discgenics.com.
