On December 23, the FDA announced the approval of the first-ever therapy for SMA. Spinraza™ (nusinersen) will serve not only as a treatment, but also addresses the underlying genetic cause of SMA. The approval from the FDA for all SMA — pediatric and adult — is the broadest possible label, with no restrictions.
How does Spinraza™ work?SMA is caused by a mutation in the survival motor neuron gene 1 (SMN1). In a healthy person, this gene produces a protein—called survival motor neuron protein or SMN protein—that is critical to the function of the nerves that control our muscles. Without it, those nerve cells cannot properly function and eventually die, leading to debilitating and often fatal muscle weakness.
All individuals affected by SMA have at least one copy of survival motor neuron gene 2 (SMN2), often referred to as the SMA "backup gene." Due to a splicing error, most of the SMN protein made by SMN2 is missing an important piece, called exon 7. Antisense drugs are small snippets of synthetic genetic material that bind to ribonucleic acid (RNA), so they can be used to fix splicing errors in genes such as SMN2. Spinraza™ is antisense oligonucleotide that targets SMN2, causing it to make more complete SMN protein.
The studies behind Spinraza™The FDA approved Spinraza™ based on data from multiple clinical studies which included more than 170 individuals with SMA. Our very own Kaiden was involved in one of these clinical studies.
The data package included the interim analysis of ENDEAR, a Phase 3 controlled study evaluating Spinraza™ in infantile-onset, as well as open-label data from uncontrolled studies in pre-symptomatic and symptomatic patients with, or likely to develop, Types 1, 2 and 3 SMA. In ENDEAR, a pivotal controlled clinical study, infantile-onset SMA patients treated with Spinraza™ achieved and sustained clinically meaningful improvement in motor function compared to untreated study participants. In addition, a greater percentage of patients on Spinraza™ survived compared to untreated patients.
In open-label uncontrolled studies, some patients achieved milestones such as ability to sit unassisted, stand or walk when they would otherwise be unexpected to do so and maintained milestones at ages when they would be expected to be lost. The overall findings of these studies support the effectiveness of Spinraza™ across the range of SMA patients, and appear to support the early initiation of treatment.