Ferring Pharmaceuticals and Seikagaku Corporation announced positive data from two Phase 3 trials evaluating SI-6603 (condoliase) for radicular leg pain associated with lumbar disc herniation (LDH). The results, presented at the North American Spine Society’s (NASS) Annual Meeting, indicated significant improvements in leg pain compared to sham or placebo. The U.S. Phase 3 study results have also been published in The Spine Journal.
Phase 3 Trial Results
The double-blind, sham or placebo-controlled Phase 3 studies randomized patients with LDH to a single intradiscal injection of either SI-6603 1.25 Units or control (sham injection for the U.S. study; placebo injection for the Japanese study), followed by 52 weeks of observation. The modified intention-to-treat population in the U.S. study included 341 participants (SI-6603 n=169; sham n=172), while the Japanese study included 163 participants (SI-6603 n=82; placebo n=81).
Both studies met their primary endpoint, demonstrating a significantly greater change from baseline (CFB) in worst leg pain at Week 13 compared to the control groups. In the U.S. study, the least squares mean (LSM) difference was -7.5 (p=0.0263), and in the Japan study, it was -15.2 (p=0.001).
Expert Commentary
“Treatment for radicular leg pain associated with lumbar disc herniation is currently limited to conservative pain management and physical therapy or surgery,” said Kee Kim, MD, University of California, Davis. “The data from these two Phase 3 studies further support the potential of SI-6603 as a therapeutic option for the millions of Americans suffering from the debilitating impact of this condition.”
Safety Profile
The most common treatment-emergent adverse events (TEAEs) in the U.S. trial were spinal magnetic resonance imaging abnormalities (SI-6603 28.1%; sham 9.2%) and back pain (SI-6603 19.2%; sham 12.6%). In the Japan trial, the most common TEAEs were back pain (SI-6603 36.6%; placebo 33.3%) and leg pain (SI-6603 25.6%; placebo 35.8%). There were no treatment-related serious adverse events (SAEs) with SI-6603 in the U.S. study. In the Japan study, one SAE (back pain) was considered potentially related to SI-6603.
Study Details
The U.S. trial, known as the Discovery 6603 clinical trial (NCT03607838), was a randomized, double-blind, sham-controlled, parallel Phase 3 study. Participants aged 30 to 70 years with contained posterolateral LDH and radicular leg pain, who had inadequate pain improvement despite more than six weeks of conservative treatment, were included. The primary endpoint was the CFB to Week 13 in worst leg pain, assessed by Visual Analogue Scale (VAS).
The Japanese study was a randomized, double-blind, placebo-controlled trial with similar endpoints and assessments.
About Lumbar Disc Herniation and SI-6603
Approximately 9 million adults in the U.S. suffer from lumbar disc herniation annually. SI-6603, containing condoliase, is an investigational product designed to reduce nerve root compression and radicular leg pain via a single intradiscal injection. It has been approved and marketed in Japan as HERNICORE® since 2018.
Ferring Pharmaceuticals holds the rights to develop, register, and commercialize SI-6603 worldwide, excluding Japan, and plans to commercialize the product in the United States upon FDA approval.
