Although the introduction of disease-modifying treatments and implementation of newborn screening has undoubtedly changed the landscape for spinal muscular atrophy (SMA), challenges remain to optimize diagnostic and treatment processes, explain the researchers of a new paper published in Frontiers in Neurology.
As of September 2022, all but 2 states had implemented newborn screening programs, accounting for 98% of births in the United States. Together with the availability of multiple therapies—nusinersen, onasemnogene-abeparvovec, and risdiplam—newborn screening programs have allowed for early initiation of treatment for presymptomatic and minimally symptomatic children.
“Although great progress has been made to date, there continues to be a gap in the implementation of newborn screening for SMA,” wrote the researchers. “Screening programs have not reached all states, and in addition, there is a lack of clear guidance regarding the minimum or ideal personnel necessary for the adequate execution of this process. For example, specialists need to be involved, and there needs to be an acceptable and ideal time to diagnosis and time to therapy.”
The recent introduction of methods for early diagnosis and rapid introduction of these 3 treatments have left unknowns about the ideal infrastructure needed within health care systems and for supporting implementation, as well as the medical personnel and resources needed for cost-effective care, explained the researchers .
Implementation of newborn screening interventions, wrote the group, should be guided by a variety of factors, ranging from the state’s size and health care infrastructure to provider factors such as laboratory personnel, methodology, and preparedness of designated diagnostic centers. For example, the state laboratory in Florida only reports SMN1 copy number, requiring early referral to identify SMN2 copy number.
Time to treatment is also affected by insurance approval, which may take weeks, and in some cases requires the patient to meet a more rigorous set of criteria than those identified by the FDA. Challenges are also posed by the treatments themselves, with gaps in knowledge of long-term implications, as most research has focused on the short-term effects.
“Long term safety data are scarce given the relative short duration of postmarketing approval. Animal studies have raised concern about the risks related to [adeno-associated viral vector] viruses and potential harm related to SMN overexpression at high doses, but literature in humans is lacking,” detailed the researchers. “Safety monitoring should be the responsibility of the health care teams and pharmaceutical companies, with participation from health insurance companies and governmental agencies, creating a challenging but ideal opportunity for the application of implementation science frameworks.”
Efficacy measures included in SMA treatment studies often report on neuromotor milestones, ventilator free time, and overall survival. Meanwhile, little data offer insight on improvement of dysphagia, sleep disorder breathing, and scoliosis.
“With the common goal to provide optimal care for patients with SMA, diagnostic and treatment centers should work together along with patients and their families, clinicians, pharmaceutical companies and governmental agencies to ensure not only timely treatment and follow-up,” the study authors concluded, “but also the development of the processes necessary for the evaluation of outcomes beyond efficacy and safety, such as cost-effectiveness and program sustainability.
Leon-Astudillo C, Byrne B, Salloum R. Addressing the implementation gap in advanced therapeutics for spinal muscular atrophy in the era of newborn screening programs. Front Neurol. Published online December 12, 2022. doi:10.3389/fneur.2022.1064194