Highly significant positive top-line results from a Phase III pivotal trial for SP 102 to treat sciatica.- Scilex Holding Company.

The C.L.E.A.R. Program trial has met the primary efficacy and key secondary efficacy endpoints with highly statistical significance: i. For the primary endpoint of change in average daily pain (as measured by the Numeric Pain Rating Scale) in the affected leg over 4 weeks following the initial injection the LS Mean (SE) group difference of -1.08 (0.17) compared to placebo with a p-value <0.001. ii. the two key secondary endpoints assessing oswestry disability index (odi) and time to open-label repeat injection have also demonstrated highly statistically significant results for sp 102. the ls mean (se) group difference in odi compared to placebo at week 4 was -6.28 (1.49) with a p-value><0.001. a cox proportional hazard model showed significantly longer duration of initial sp 102 (semdexa) treatment compared to placebo hazard ratio (95% ci) 0.49 (0.36, 0.65), with a p-value><0.001.></0.001.></0.001.></0.001.>

Scilex expects SP 102 (Semdexa) to be the first FDA-approved non-opioid epidural injection for sciatica with the potential to replace the current 10 to 12 million off-label epidural steroid injections administered each year in the USA, where more than 30 million people suffer from low back and radicular pain. This population is expected to grow as the overall population ages.

C.L.E.A.R. Trial (Corticosteroid Lumbosacral Epidural Analgesia for Radiculopathy) was designed to investigate safety and analgesic effects of a single and repeat transforaminal injections of SP 102 (Semdexa) compared to placebo (saline injection).The trial enrolled 401 low back pain subjects with unilateral intervertebral disc herniation in lumbosacral spine resulting in radicular pain symptoms of moderate to severe leg pain. It is the largest known randomized well-controlled trial in sciatica using epidural steroid injections. The primary endpoint of change in average daily pain in the affected leg over 4 weeks following the initial injection had demonstrated LS Mean (SE) group difference of -1.08 (0.17) compared to placebo with a p-value <0.001.></0.001.>

The two key secondary endpoints assessing Oswestry Disability Index (ODI) and Time to open-label repeat injection had also demonstrated highly statistically significant results . The LS Mean (SE) group difference in ODI compared to placebo at week 4 was -6.28 (1.49) with a p-value <0.001. following the initial 4-week observation period, subjects with moderate to severe radicular pain could receive an open-label repeat injection of sp 102 (semdexa). between weeks 4 and 12, repeat injections were administered to 67% of subjects who initially received placebo treatment and 46% of subjects who initially received active treatment. a cox proportional hazard model showed significantly longer duration of initial sp 102 (semdexa) treatment compared to placebo hazard ratio (95% ci) 0.49 (0.36, 0.65), with a p-value><0.001. sp 102 (semdexa) demonstrated a very clean safety profile with no identified safety risks. there were no adverse events of special interest reported (paraplegia, hematoma, injection) associated with epidural steroid injections. there were no saes related to the drug or injection procedure.></0.001.></0.001.>

Scilex intends to use the results from this pivotal Phase III trial to discuss with the FDA in 2022 a licensure application and Breakthrough Designation Status for the high unmet need sciatica indication for which no treatments have been approved in the U.S.

By 2022, the overall estimated number of epidural steroid injection (ESI) procedures in the U.S. is expected to be 12.1 million across all Medicare and private coverage patients, with lumbar radiculopathy/sciatica procedures comprising approximately 88% of all ESIs administered, according to a proprietary study by Syneos Health Consulting. Despite widespread utilization of ESIs, concerns persist in the market about particulate and solution steroids and potential side effect and safety concerns (e.g., stroke) from current off-label use. Opioid prescriptions account for about 40% of the chronic back pain market and carry a well-known risk of abuse and misuse, underscoring the need for alternate pain therapies without the medical and societal challenges. As a result, a significant unmet medical need exists within the market for a novel, non-particulate ESI formulation that demonstrates safety and effectiveness in controlled clinical trial evaluations.

In the U.S., more than 30 million people suffer from low back and radicular pain. This population is expected to grow as the overall population ages. Many patients experience moderate to severe pain with intolerance of and/or inadequate response to current analgesic therapies such as opioids and nonsteroidal anti-inflammatory drugs (NSAIDs). There is a great need for highly effective analgesic medications to provide patient relief without the toxicity and tolerability challenges of NSAIDs and opioids.

Chronic pain affects 116 million Americans and costs the U.S. as much as $635 billion each year, according to a recent report from the Institute of Medicine (IOM) that called for changes in how chronic pain is managed and nearly 30 million patients suffer from lower back pain in the U.S. Government agencies, physicians, patients, and payers are looking for alternatives to opioids to reduce the risk of dependency or addiction, and serious side effects (such as respiratory depression and constipation), while still offering potent solutions for people living with chronic pain.