INTRODUCTION: Chemonucleolysis recently re-emerged as a nonsurgical treatment for lumbar disc herniation (LDH). SI-6603 (condoliase; 1.25 unit [U]), a glycosaminoglycan-degrading mucopolysaccharidase, is approved in Japan for LDH-associated radicular leg pain. Efficacy and safety data from two pivotal phase 3 studies alongside integrated safety data from phase 2 and 3 clinical trials in the United States (US) and Japan are summarized.
METHODS: In two studies in the US (NCT03607838) and Japan, participants with radicular leg pain and contained posterolateral LDH were randomized 1:1 to receive a single injection of condoliase (1.25 U) or control (US: sham injection; Japan: placebo injection). The primary endpoint was the change from baseline (CFB) to Week 13 in worst leg pain assessed by visual analogue scale. The integrated safety analysis used data from 6 completed phase 2/3 clinical trials (2 open-label) of condoliase (≥1.25 U).
RESULTS: The US (N=341) and Japanese studies (N=163) met the primary endpoint, with condoliase showing significantly greater CFB in worst leg pain at Week 13 vs sham (p=0.0263) and placebo (p=0.001), respectively. In the US trial, no treatment-related serious adverse events (SAEs) occurred; one SAE (back pain) was considered possibly related to condoliase in the Japanese trial. In the integrated safety analysis (condoliase ≥1.25 U; N=1679), 69.0% of participants reported treatment-emergent adverse events (TEAEs), 4.9% SAEs, and 0.8% TEAEs leading to discontinuation.
DISCUSSION: Condoliase was effective in improving radicular leg pain at Week 13 in adults with LDH and was well tolerated, demonstrating its therapeutic potential in the US.