A new experimental method of delivering Spinraza (nusinersen) to people with spinal muscular atrophy (SMA) could reduce both the costs and burden of the treatment, potentially allowing more patients access to the therapy, researchers say.
The new approach was outlined in the study, “Preliminary Safety and Tolerability of a Novel Subcutaneous Intrathecal Catheter System for Repeated Outpatient Dosing of Nusinersen to Children and Adults With Spinal Muscular Atrophy,” published in the Journal of Pediatric Orthopaedics.
SMA is caused by mutations in the SMN1 gene, which leads to reduced production of the SMN protein. While humans have a second survival motor neuron gene (SMN2) capable of producing SMN, a slight difference in its DNA sequence makes 90 percent of the resulting SMN protein shorter and nonfunctional.
Spinraza, developed by Biogen, is the only approved treatment for almost all types of SMA in several countries including the U.S., the European Union, Australia, Brazil, Japan, Switzerland, South Korea, Canada, and Chile. It increases the ability of the SMN2 gene to produce a full-length SMN protein, potentially restoring its levels and function.
Spinraza is currently administered through an injection into the cerebrospinal fluid (the fluid in the spine) — a procedure called intrathecal injection — every four months throughout a patient’s life. Intrathecal injection allows Spinraza to easily reach the central nervous system (spinal cord and brain) that is mainly affected by SMA.
However, this type of administration not only presents safety and accessibility challenges in many SMA patients with spine deformities, it can also cause complications, especially in newborns and young children.
To address these issues, researchers and clinicians at the Clinic for Special Children in Strasburg, Pennsylvania, and the Nemours/A.I. duPont Hospital for Children in Wilmington, Delaware, have developed and tested a new method of Spinraza delivery.
The alternative method is based on a subcutaneous intrathecal catheter (SIC) system that connects a catheter inserted in the spinal cord to an implantable infusion port — a self-sealing silicone disk placed under the skin that can be punctured with a special needle many times to administer a therapy.
Researchers implanted the SIC system in 10 SMA patients with advanced disease and spine deformities, between 5 and 30 years old, with 3 copies of SMN2, and evaluated its safety and tolerability over three sequential doses of Spinraza.
The device was inserted in less than two hours and was well-tolerated in all patients, who stayed in the hospital, on average, for less than two and a half days. All doses of Spinraza were administered in less than 20 minutes on the first attempt, and required no sedation, medication to relieve pain, ultrasound guidance, or respiratory precautions.
These preliminary findings suggest that the SIC system is a relatively safe and well-tolerated delivery method for Spinraza in SMA patients. In addition, the team noted that this method significantly lowers the cost of Spinraza administration by five to 10 times.
The researchers believe that if these results are confirmed in larger trials of longer duration, twice as many SMA patients may be able to receive Spinraza through this alternative method.