The DGX-A01 study met its primary safety and efficacy endpoints in its highest dose cohort of IDCT.
The FDA has granted regenerative medicine advanced therapy (RMAT) designation to DiscGenics’ IDCT (rebonuputemcel) cell therapy, which recently demonstrated safe and durable improvements in low back pain, function, quality of life, and pain medication usage by 12 weeks in patients with lumbar degenerative disc disease (DDD) in 2-year data from the phase 1/2 DGX-A01 study (NCT03347708).1,2
"These clinical results demonstrate the incredible potential of DiscGenics's IDCT to safely treat not only the pain and disability associated with DDD with a single injection, but also to address the underlying cause of the disease—the degenerating disc. This is unlike any treatment I have seen in 30 years of practice and unlike any treatment currently available on the market," Matthew F. Gornet, MD, Board Certified Spine Surgeon, The Orthopedic Center of St. Louis, said in a statement.1 "The improvements we observed in disc volume through MRI image analysis suggest DiscGenics's IDCT produces a regenerative effect within the degenerating disc which indicates the ability to halt and possibly reverse the progression of DDD."
DGX-A01 is evaluating the safety and preliminary efficacy of IDCT allogeneic discogenic progenitor cell therapy in 60 participants with symptomatic lumbar DDD versus vehicle and saline controls. The trial enrolled participants from 13 centers across 12 states. It used measures including 100-mm Visual Analog Scale (VAS), Oswestry Disability Index Questionnaire (ODI), and EQ-5D quality of life index score. At 2 years, overall patient follow-up was 85%.
“This designation represents a critical validation of our novel approach to utilizing a manufactured live progenitor cell population derived from donated adult human intervertebral disc tissue to treat disc degeneration,” Flannagan commented on the RMAT designation.2 “As committed stewards of this technology, we look forward to partnering with the FDA to expedite our drug development program and to ultimately realizing the potential of IDCT to address the unmet medical needs of millions of patients with this painful and debilitating condition.”
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The new data from DGX-A01 announced by DiscGenics included the announcement that the study had met its primary safety endpoint in the high-dose cohort of 20 participants treated with 9,000,000 cells/mL, with no observed treatment-emergent serious adverse events (AEs).1 The primary efficacy endpoint was previously reported to be reached, with statistically significant improvements in back pain scores by over 30% as measured on a 100mm VAS observed in the high dose IDCT group at 52 weeks (–62.79%, P =.0005). A smaller, significant decrease in VAS was also observed in the vehicle control group.
Clinically meaningful improvements in pain (measured by VAS), function (measured by ODI), and quality of life (measured by EQ-5D)seen in the high-dose group were sustained at 6 months, 1 year, 1.5 years, and 2 years post percutaneous injection. Investigators also observed statistically significant improvements in disc volume, with MRI imaging-derived mean changes in disc volume increasing steadily from baseline and reaching statistical significance at week 52 (249.01 mm3, P = .0284) and week 104 (402.1 mm3, P = .028). In the control group, disc volume decreased although not significantly. This treatment group also showed a decrease in both opioid and nonsteroidal anti-inflammatory drug use.
Participants treated with 3,000,000 cell/mL (n = 20) experienced trends of improvement in the measured clinical outcomes, but these were inconsistent. Ten participants in the vehicle control group also had some pain relief as measured by 100mm VAS, but this was not associated with clinically meaningful improvements in function or quality of life. The 10 participants in the saline placebo control group did not have any significant or meaningful improvements in outcomes.
"We are very encouraged by the final two-year results of this study," Flagg Flanagan, chief executive officer and Chairman of the Board, DiscGenics, added to the statement.1 "The significant and durable improvements we saw in pain, function, quality of life, disc volume, and concomitant pain medication usage are critical indicators of the potential for IDCT to change the paradigm of care for patients with DDD."