Condoliase(Seikagaku Corp.)

PARSIPPANY, N.J.--( BUSINESS WIRE )--Ferring Pharmaceuticals and its clinical development partner, Seikagaku Corporation (Seikagaku), today announced the presentation of data from two Phase 3 trials evaluating the efficacy and safety of SI-6603 (generic name: condoliase), an investigational product being studied for the treatment of radicular leg pain associated with lumbar disc herniation (LDH). The podium presentation at the North American Spine Society’s (NASS) Annual Meeting included results from one study conducted in the U.S. and one in Japan. In addition, The Spine Journal has published the results of the pivotal U.S. Phase 3 study. NASS Presentation In the double-blind, sham or placebo controlled Phase 3 studies, patients with LDH were randomized to receive either a single intradiscal injection of SI-6603 1.25 Units or control (sham injection for U.S. study; placebo injection for 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), and the study population in Japan included 163 participants (SI-6603 n=82; placebo n=81). The studies met their primary endpoint, showing significantly greater change from baseline (CFB) in worst leg pain at Week 13 compared to sham (U.S.) / placebo (Japan) (least squares mean [LSM] difference: -7.5 [p=0.0263] for the U.S. study and -15.2 [p=0.001] for the Japan study). “ Treatment for radicular leg pain associated with lumbar disc herniation is currently limited to conservative pain management and physical therapy or surgery. 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, ” said Kee Kim, MD, University of California, Davis. 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, and in the Japan study, one SAE (back pain) was considered potentially related to SI-6603. About the Phase 3 Trial in the U.S. In this randomized double-blind, sham-controlled, parallel Phase 3 study — known as the Discovery 6603 clinical trial (NCT03607838) — participants were randomized 1:1 to receive either SI-6603 (1.25 U) or sham injection followed by 52 weeks of observation. The primary endpoint was defined as the CFB to Week 13 in worst leg pain during the past 24 hours averaged over the previous seven days, as assessed by Visual Analogue Scale, a pain rating score from 0 – 100 with a higher score indicating greater pain intensity. Key secondary endpoints included the CFB in average worst leg pain at 52 weeks, percentage of participants with negative straight leg raise test, and 50% responder rates for worst leg pain and Oswestry Disability Index (ODI). Since the key secondary endpoint of change in average worst leg pain at Week 52 was not significant, the serial gatekeeping testing algorithm dictated that there were no significant group differences for Week 13 herniation volume or ODI score regardless of their p-values. Endpoints were assessed using a mixed model for repeated measures (MMRM) analysis of the modified intention-to-treat population (mITT). The trial included U.S. participants ages 30 to 70 years old who had contained posterolateral LDH with the chief complaint being unilateral radiculopathy/radicular leg pain and inadequate improvement in pain despite more than six weeks of conservative treatment. Among 352 randomized participants, 341 constituted the mITT population (SI-6603 n=169; sham injections n=172). About the Phase 3 Trial in Japan In this randomized, double-blind, placebo-controlled study, participants were randomized 1:1 to receive either a single injection of SI-6603 (1.25U) or placebo injection, followed by 52 weeks of observation. The primary endpoint was the CFB to Week 13 in average worst leg pain during the past 24 hours over the previous seven days, as assessed by Visual Analogue Scale, a pain rating score from 0 – 100 with a higher score indicating greater pain intensity. Secondary endpoints included CFB up to Week 52 in average worst leg pain, herniation volume and ODI score. Endpoints were assessed using an analysis of covariance model. About Lumbar Disc Herniation About 9 million adults in the U.S. suffer from lumbar disc herniation each year. A disc herniation is a displacement of the gel-like inner core of the intervertebral disc, called the nucleus pulposus, through its external membrane (annulus fibrosus) due to wear and tear, aging or sudden injury. As a result of this displacement, the disc presses on the spinal nerve, often producing pain. 1,2 About SI-6603 SI-6603, which contains condoliase as its active pharmaceutical ingredient, is an investigational product being studied for the treatment of radicular leg pain associated with lumbar disc herniation via a single, direct intradiscal injection. SI-6603 (condoliase) is designed to reduce nerve root compression and thereby the radicular leg pain. SI-6603 was developed by Seikagaku. Marketing approval for SI-6603 in Japan was obtained from the Japanese Ministry of Health, Labour and Welfare in March 2018 and SI-6603 has been marketed in Japan only as HERNICORE ® 1.25 units for intradiscal injection through Seikagaku's Japanese sales partner Kaken Pharmaceutical Co., Ltd. (Tokyo, Japan) since August 1, 2018. 3 Alliance with Seikagaku Seikagaku and Ferring entered into a license agreement for SI-6603 in August 2016. Ferring plans to commercialize the product in the United States upon FDA approval and has received further rights to develop, register and commercialize SI-6603 worldwide, excluding Japan. About Ferring Pharmaceuticals Ferring Pharmaceuticals is a privately-owned, research-driven, specialty biopharmaceutical group committed to building families and helping people live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, and in areas of gastroenterology and orthopaedics. We are at the forefront of innovation in microbiome-based therapeutics and uro-oncology intravesical gene therapy. Our company was founded in 1950 and is headquartered in Saint-Prex, Switzerland. Ferring employs more than 7,000 people worldwide and markets its medicines in over 100 countries. Ferring USA is based in Parsippany, New Jersey, and employs more than 900 employees. For more information, please visit www.ferringusa.com , call 1-888-FERRING (1-888-337-7464), or connect with us on LinkedIn and X (Twitter) . References: Vialle LR, Vialle EN, Suárez Henao JE, Giraldo G. Lumbar Disc Herniation. Rev Bras Ortop . 2015 Nov 16;45(1):17-22. doi: 10.1016/S2255-4971(15)30211-1. PMID: 27019834; PMCID: PMC4799068. Herniated Disk in the Lower Back. OrthoInfo. American Academy of Orthopaedic Surgeons. Available at: https://orthoinfo.aaos.org/en/diseases–conditions/herniated-disk-in-the-lower-back/ . Accessed May 23, 2023. Press Release. Seikagaku and Kaken Announce the Launch of HERNICORE ® 1.25 Units for Intradiscal Injection in Japan. July 31,2018. Available at: https://www.seikagaku.co.jp/en/news/news-6617037418084939174/main/0/link/20180731-e.pdf . Accessed May 24, 2023.

PARSIPPANY, NJ. USA I July 15, 2024 I Ferring Pharmaceuticals and its clinical development partner, Seikagaku Corporation (Seikagaku), today announced the presentation of a Phase 3 data analysis evaluating the early treatment response to SI-6603 (generic name: condoliase), an investigational product being studied for the treatment of radicular leg pain associated with lumbar disc herniation (LDH). The research, presented at the American Society of Pain and Neuroscience (ASPN) Annual Meeting, also included an analysis of healthcare resource utilization and costs associated with LDH surgery. In the analysis (poster number 44) of the double-blind, sham-controlled, Phase 3 study, patients with LDH were randomized to receive either a single intradiscal injection of SI-6603 1.25 Units or a sham injection, followed by 52 weeks of observation (Weeks 1, 2, 4, 6, 13, 26, 39, 52). The modified intention-to-treat (mITT) population included 341 participants (SI-6603 n=169; sham n=172). The study met its primary endpoint, showing significantly greater improvement vs. sham in worst leg pain at Week 13 (least squares mean [LSM] difference: -7.5; p=0.0263) with notable differences as early as Week 4 (-6.0; p=0.0418) and Week 6 (-7.4; p=0.0146). Beginning at Week 1, more participants in the SI-6603 group vs. sham had a negative straight leg raise test (p=0.0054) which was sustained to Week 52 (p=0.0003). Notable differences in 50% responders for worst leg pain (i.e., meaning a ≥50% improvement from baseline) also favored SI-6603 vs. sham at Week 4 (p=0.0189), Week 6 (p=0.0297) and Week 13 (p=0.0165). There were no treatment-related serious adverse events with SI-6603. “ The early treatment response observed in this analysis is promising for those suffering from radicular leg pain resulting from lumbar disc herniation and who may experience severe, debilitating pain which can affect their mobility, and impact their ability to go about their usual activities. This is an area of significant unmet patient need and if approved, SI-6603, which targets the source of radicular leg pain, may help fill a current treatment gap between conservative pain management and surgery, ” said Raza Ahmed, MD, Senior Director, Medical Affairs, Specialty/Orthopaedics, Ferring USA. An analysis (poster number 171) of healthcare resource utilization and costs for patients with LDH who underwent LDH surgical procedures was also presented at ASPN 2024. Of the more than one million patients with LDH in the medical claims database, 58,328 underwent LDH surgeries within one year of initial diagnosis. During the first year following initial diagnosis, patients treated with surgery had more LDH-related outpatient visits than non-surgery-treated patients (mean: 17.0 vs. 10.3) and a higher proportion of LDH-related hospitalizations (36.3% vs. 0.9%). Nearly half (48.2%) of surgery-treated patients received at least one epidural steroid injection (ESI) within the first year, with 49% of them receiving multiple ESIs. Total LDH-related healthcare cost during the first year was $35,018 for surgery-treated patients versus $4,384 for non-surgery-treated patients. The average cost for LDH surgery was $25,993 per procedure ($25,815 for the first surgery and $27,587 for subsequent procedures). About one in three LDH surgeries (35.7%) were performed in an inpatient setting, with a cost three times higher than an outpatient setting ($46,411 vs. $14,666). About the Phase 3 Trial Data Analysis In this double-blind, sham-controlled, parallel Phase 3 study — known as the Discovery 6603 clinical trial (NCT03607838) — participants were randomized 1:1 to receive either SI-6603 (1.25 U) or sham injection followed by 52 weeks of observation. The primary endpoint was defined as the change from baseline to Week 13 in average worst leg pain during the past 24 hours over the previous seven days, as assessed by Visual Analogue Scale, a pain rating score from 0 – 100 with a higher score indicating greater pain intensity. Key secondary endpoints included the change from baseline in average worst leg pain at 52 weeks, percentage of participants with negative straight leg raise test, and 50% responder rates for worst leg pain and Oswestry Disability Index. Endpoints were assessed using a mixed model for repeated measures analysis on the modified intention-to-treat population, which represented all randomized participants who received the study injection analyzed according to the assigned treatment. Missing data was handled using a mixed-effect model, without explicit imputation. The trial included U.S. participants ages 30 to 70 years old who had contained posterolateral LDH with the chief complaint being unilateral radiculopathy/radicular leg pain and inadequate improvement in pain despite more than six weeks of conservative treatment. Among 352 randomized participants, 341 constituted the mITT population (SI-6603 n=169; sham injections n=172). About the Healthcare Utilization and LDH Surgery Analysis For this study, investigators reviewed medical claims data from the IQVIA PharMetrics® Plus database of 1,086,552 adults ages 30 to 70 years diagnosed with LDH between 01/01/2018 and 03/31/2022. Eligible patients had continuous medical and pharmacy enrollment for at least 6 months before and 12 months after the initial diagnosis. Among the patients with LDH, 58,328 patients underwent LDH surgeries within one year of initial diagnosis. On average, these patients were approximately 52 years old (51.9±9.9) with most comorbidities that were mild to moderate in severity, based on a mean Charlson Comorbidity Index score of 1.3±1.8. About Lumbar Disc Herniation About 9 million adults in the U.S. suffer from lumbar disc herniation each year. A disc herniation is a displacement (leakage) of the gel-like inner core of the intervertebral disc, called the nucleus pulposus, through its external membrane (annulus fibrosus) due to wear and tear, aging or sudden injury. As a result of this displacement, the disc presses on the spinal nerve, often producing pain. 1,2 About SI-6603 SI-6603, which contains condoliase as its active pharmaceutical ingredient, is an investigational product being studied for the treatment of radicular leg pain associated with lumbar disc herniation via a single, direct intradiscal injection. SI-6603 (condoliase) reduces nerve root compression and thereby pain. SI-6603 was developed by Seikagaku. Marketing approval for SI-6603 in Japan was obtained from the Japanese Ministry of Health, Labour and Welfare in March 2018 and SI-6603 has been marketed in Japan only as HERNICORE ® 1.25 units for intradiscal injection through Seikagaku Corporation’s Japanese sales partner Kaken Pharmaceutical Co., Ltd. (Tokyo, Japan) since August 1, 2018. 3 Alliance with Seikagaku Seikagaku and Ferring entered into a license agreement for SI-6603 in August 2016. Ferring plans to commercialize the product in the United States and has received further rights to develop, register and commercialize SI-6603 worldwide, excluding Japan. About Ferring Pharmaceuticals Ferring Pharmaceuticals is a privately-owned, research-driven, specialty biopharmaceutical group committed to building families and helping people live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, and in areas of gastroenterology and orthopaedics. We are at the forefront of innovation in microbiome-based therapeutics and uro-oncology intravesical gene therapy. Our company was founded in 1950 and is headquartered in Saint-Prex, Switzerland. Ferring employs more than 7,000 people worldwide and markets its medicines in over 100 countries. Ferring USA is based in Parsippany, New Jersey, and employs more than 900 employees. For more information, please visit www.ferringusa.com , call 1-888-FERRING (1-888-337-7464), or connect with us on LinkedIn and X (Twitter) . References: 1 Vialle LR, Vialle EN, Suárez Henao JE, Giraldo G. Lumbar Disc Herniation. Rev Bras Ortop . 2015 Nov 16;45(1):17-22. doi: 10.1016/S2255-4971(15)30211-1. PMID: 27019834; PMCID: PMC4799068. 2 Herniated Disk in the Lower Back. OrthoInfo. American Academy of Orthopaedic Surgeons. Available at: https://orthoinfo.aaos.org/en/diseases–conditions/herniated-disk-in-the-lower-back/ . Accessed May 23, 2023. 3 Press Release. Seikagaku and Kaken Announce the Launch of HERNICORE® 1.25 Units for Intradiscal Injection in Japan. July 31,2018. Available at: https://www.seikagaku.co.jp/en/news/news-6617037418084939174/main/0/link/20180731-e.pdf . Accessed May 24, 2023. SOURCE: Ferring Pharmaceuticals