Back pain is a pervasive health problem and a significant area of healthcare expenditure. Epidural steroid injections (ESI) are commonly given to treat back pain after more conservative treatment options have failed. ESI's are expensive and short-lasting. Repeat injections are common over the first 3 months of treatment. All are done off-label with generic, injectable steroids. Physicians historically preferred the water-insoluble steroid suspensions, such as methylprednisolone acetate, to prolong the duration of steroid exposure compared to a water-soluble steroid. Recently, the water-insoluble steroid suspensions have been linked to paralysis or death after failed epidural injections that resulted in delivery to an artery that passes through the epidural space and which supplies blood to the spinal cord. The particles in these water-insoluble steroid suspensions are significantly larger than capillary beds and are believed to result in vascular occlusion. Researchers have replicated a direct arterial injection in pigs and have shown that such an injection leads to neurological injury with a water-insoluble steroid suspension but not with a water-soluble steroid solution. SpineThera aims to demonstrate feasibility of a sustained-release, biodegradable microparticle-steroid formulation that will not result in vascular occlusion if inadvertently injeced into a spinal artery. Such a formulation may eliminate the need for repeat ESI's over the drug release time period, or longer, and eliminate the risk of paralysis associated with some generics. The duration of drug release is intended to be significantly longer than from the generic, water-insoluble steroid suspensions. SpineThera proposes to utilize previously established in-vitro drug release tests that have been compared to in-vivo release profiles to demonstrate that 28-days of drug release can be achieved from a biodegradable microparticle formulation whose particle size is small enough to not lead to direct capillary bed occlusion. Variables such as biodegradable polymer chemistry, microencapsulation processing technique, and physical form of the active pharmaceutical ingredient will be studied utilizing a Quality by Design approach. The biodegradable microparticles will further include a surface modification intended to prevent agglomeration and platelet adhesion. Formulations that meet the 28-day drug release, particle size, non-aggregating, and surface chemistry criteria will be further studied. The selected formulations will be given as a direct injection into a spinal artery of a pig (n=13). Vascular occlusion will be assessed by angiography and compared to injections of a water-insoluble steroid suspension (which has shown occlusion in previous study) and a water- soluble steroid solution (non-occluding in previous study).
The proposed drug may eliminate the need repeat for epidural steroid injections to treat back pain. Direct healthcare spending may be reduced by $3.6 billion, more than 30%. Furthermore, the proposed drug may eliminate the risk of paralysis that has been documented with epidural injection of some generic steroids.
