To help clinicians and the families they serve in the decision of when to administer therapy to infants identified with SMA via newborn screening, Cure SMA convened a working group comprised of 15 SMA experts to develop treatment guidelines. These guidelines, “Treatment Algorithm for Infants Diagnosed with Spinal Muscular Atrophy through Newborn Screening,” were originally published in the Journal of Neuromuscular Diseases in May 2018. Today, we are pleased to share an update to these recommendations, expanding the number of newborns diagnosed with SMA via newborn screening that are advised to seek immediate treatment. These revised recommendations were published online in the Journal of Neuromuscular Diseases.
The Working Group first developed a treatment algorithm for the administration of an SMN-upregulating treatment, based upon genotype following a positive identification of SMA through newborn screening. The Working Group unanimously recommended immediate treatment for individuals with SMA who have two or three copies of the survival motor neuron gene 2 (SMN2)—also known as the SMA “back-up gene”—as supported by the strong positive results seen in pre-symptomatic infants in the NURTURE trial.
Previously, the Working Group did not reach a consensus, and thus, did not issue a recommendation on whether to immediately treat or conduct watchful waiting for infants with four copies of SMN2. The group was nearly equally split on this decision and, therefore, referred the decision to the infant’s healthcare provider. The recommendation was for a personalized decision about which course to take for these patients by their parents and physicians.
In September 2019, Cure SMA reconvened the multidisciplinary Working Group to reassess the treatment algorithm. At this time, there was agreement that enough new clinical data and real-world experience was available to update their position to recommend immediate treatment for infants diagnosed with SMA via newborn screening with four copies of SMN2.
This updated recommendation took into account the recent publication of data from Biogen’s NURTURE clinical trial showing the dramatic impact from early Spinraza treatment—with data showing that treatment under 6 weeks of age in patients with two or three copies of SMN2 is significantly better than treatment after 6 weeks of age. Patients enrolled in this trial with two copies of SMN2 have a dramatically altered disease course: 100% alive, 100% sitting, 88% walking with assistance, 77% walking independently, and none needing the use of permanent ventilation assistance. Critically, disease has been largely prevented in the patients with three copies of SMN2, as these patients have met motor milestones on schedule and currently do not manifest clinical signs of SMA. The Working Group argues the same predicted outcomes seen in patients with three copies of SMN2 would apply for patients with four copies of SMN2. With early treatment, disease would be mostly eradicated in pre-symptomatic patients with four copies of SMN2. Additionally, the SMN1 replacement gene therapy (Zolgensma) is now approved for all patients under two years of age, no matter the number of SMN2 copies, is also pushing toward treatment over watchful waiting.
Decisions about initiation of treatment, when not done immediately, are still dependent on the presence of any clinical or subclinical signs of SMA, such as weakness or decrease in amplitude of the compound muscle action potential (CMAP). These symptoms are reflective of already occurring motor neuron dysfunction or loss. Critically, the Working Group notes that the loss of even a small number of motor neurons is unacceptable when effective treatment is available, as this loss cannot be reversed after onset but can be prevented with earlier treatment.