GLP Toxicology Testing and Phase 2/3 Development for a Nonopioid, Injectable Drug Product for the Treatment of Lumbosacral Radiculopathy (Sciatica)
Abstract
Over one in three Americans experiences back pain annually, resulting in significant suffering and expense. Low back pain (LBP) typically starts with a herniated disc in the lumbar (lower) spine. The vertebrae (bones of the spine) are separated and cushioned by flexible discs of connective tissue. When a disc gets worn down from an injury or over years of use, the discs can begin to push out, placing pressure on the nerves and causing significant pain and discomfort. LBP is relevant to civilians and is of great concern for the U.S. military. Epidural steroid injections (ESIs), a steroid shot given near the painful spinal nerve (epidural space), are a common treatment for back pain that is performed over 7 million times per year in the U.S.; these injections cost $4 billion in medical expenses. There are no FDA-approved drugs for ESIs; any drugs used to treat this condition are “off-label,” meaning they are approved for other diseases, such as osteoarthritis. These off-label drugs are also short-acting and repeat ESIs are common in the first 12 weeks of treatment. Off-label steroids have also rarely been linked to paralysis or death after inadvertent delivery to a spinal artery during the ESI procedure. An urgent need exists for an approved drug that provides long-term pain relief from a single injection and that addresses the safety risks of off-label drugs. SpineThera has developed a novel, sustained-release steroid drug (SX600) to treat LBP (also known as sciatica). SpineThera believes that SX600 will address the safety issues and healthcare burden observed with the current injectable drugs used to treat LBP and is aiming to be the first drug approved for this indication. One of the key features of SpineThera’s product is that a long duration of drug delivery is possible from very small microspheres, which has not been done before. The proposed project relates to two FY20 PRMRP topic areas, Musculoskeletal Health and Sustained Release Drug Delivery. With respect to Musculoskeletal Health, SX600 is being developed as an epidural steroid injection that is administered to reduce pain near a spinal nerve and is the primary treatment between conservative nondrug treatments and surgery. SX600 delivers a steroid over 60+ days and has the potential to prevent the recurrence of pain, thereby reducing the need for repeat epidural steroid injections and spinal surgery. The presented proposal is closely aligned with a second Topic Area: Sustained Release Drug Delivery. Sustained release for pain control is a listed Area of Encouragement and that directly aligns with the goals of developing SX600. Additionally, the sustained-release microspheres can be used, and are patented, as a platform technology capable of delivering other therapeutics; the duration and speed of release can be easily tuned. The requested funding will be used to run FDA-required preclinical studies needed for an IND regulatory submission and phase 3 clinical trial, including three critical animal studies. The outcomes of the preclinical testing will provide safety data that will be used to support further human clinical research. Additionally, the proposal seeks funding to de-risk the manufacturing process for a phase 3 clinical trial in the U.S. by performing critical development and scaling activities for the GMP manufacturing processes. Building on the significant development work to date, the main objective of the proposal is to advance the novel SX600 drug product through the preclinical testing phase and enable a phase 3 clinical study in patients with LBP. We have identified three specific aims to support this objective: • Aim #1: Complete animal testing in two species where SX600 is injected near the spinal cord (this is an accidental route of administration required by the FDA to be tested for safety). • Aim #2: Complete animal testing in one species in a short-term study where SX600 is injected in the epidural space (this is the intended rout
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110425
Entities
People
- Jeffrey Missling
Organizations
- SpineThera (United States)
- United States Army