Oral Presentation Sydney Spinal Symposium 2025

Background:
Lumbar disc degeneration is a leading contributor to chronic back pain. Intradiscal administration of recombinant human Growth and Differentiation Factor-6 (rhGDF-6) is a novel biological therapy under investigation for its potential to reduce pain and promote disc regeneration.

Phase I/II Study Design:
An open-label, multicenter, dose-escalation study evaluated the safety, tolerability, and preliminary efficacy of intradiscal rhGDF-6 in adults with persistent low back pain unresponsive to non-surgical care.

• Design: Single administration, sequential dosing with observation pauses
• Subjects: 8 in Phase I; up to 40 in Phase II
• Endpoints: Safety (AEs, labs, neurologic exams), clinical outcomes (ODI, EQ-5D, NRS) at 14 days, 3, 6, and 12 months
• Findings: No dose-limiting toxicities. Improvements in pain and function observed; data supported dose selection for Phase III.

Phase III Study Design:
A randomized, double-blind, placebo-controlled, multicenter trial to assess the efficacy, safety, and preliminary cost-effectiveness of intradiscal rhGDF-6.

• Design: Single dose, placebo-controlled (4.0 mg rhGDF-6 determined from Phase II)
• Subjects: Up to 250 randomized (190 active, 60 placebo)
• Endpoints:
  • Primary: Pain and disability improvement (ODI, EQ-5D, VAS)
  • Secondary: Imaging (MRI hydration, disc height), cost avoidance of surgical intervention
  • Safety: Neurological exams, labs (CBC, chemistry, CRP, ESR), AEs monitoring to 36 months
• Follow-Up: Clinic visits to 12 months; telephone check-ins at 24 and 36 months.

Conclusion:
Intradiscal rhGDF-6 has demonstrated a favorable safety profile and promising signals of efficacy in treating lumbar discogenic pain. The clinical trials will pave path towards establishing rhGDF-6 as a first-in-class injectable biological therapy for early-stage degenerative disc disease.