SMC Extends SMA Drug Access to Newborns

The Scottish Medicines Consortium (SMC) has accepted nusinersen (Spinraza, Biogen Idec) for restricted use within NHS Scotland to treat pre-symptomatic 5q spinal muscular atrophy (SMA), extending access to infants identified before symptoms develop, rather than only those already showing signs of the disease.The decision follows the rollout of routine newborn screening for SMA in Scotland, which now identifies affected infants before symptoms appear — a population for whom pre-symptomatic treatment options were previously limited. England will introduce a similar screening programme from October this year.5q SMA is an inherited, autosomal recessive disorder caused by deletion or mutation of the SMN1 gene, which reduces levels of the SMN protein needed to keep spinal motor neurons alive. A second, near-identical gene, SMN2, produces a shorter, less functional version of the protein; patients can carry between zero and eight copies of SMN2, and having fewer copies is linked to more severe disease.The end result is that neurons progressively deteriorate and die, leading to severe muscle weakness. This is usually first noticed in babies and toddlers, who may have floppy or weak arms and legs. They have difficulty sitting up, crawling, or walking; problems with breathing or swallowing; and muscle twitching or tremors. Bone and joint problems, such as scoliosis, may develop.Estimates suggest a disease frequency of 1 in 6000 live births, with a carrier frequency of 1 in 50 among Europeans.SMA presents a clinical spectrum of disease, with disease severity linked to younger age of symptom onset.9 in 10 Pre-Symptomatic Infants Able to Walk Unaided Nusinersen is an antisense oligonucleotide, which increases the proportion of exon 7 inclusion in survival motor neuron 2 messenger ribonucleic acid (mRNA) transcripts by binding to an intronic splice silencing site found in intron 7 of the SMN2 pre‑messenger ribonucleic acid (pre‑mRNA). By binding, the ASO displaces splicing factors, which normally suppress splicing. Displacement of these factors leads to retention of exon 7 in the SMN2 mRNA and hence when SMN2 mRNA is produced, it can be translated into the functional full length SMN protein.SMC approval followed a submission assessed under the orphan medicine process, with results of a phase II single-arm study in which 80% of pre-symptomatic patients with a genetic diagnosis of SMA who received nusinersen treatment did not require respiratory intervention. Additionally, 92% of patients achieved the motor milestone of walking alone. However, the SMC cautioned that direct comparative evidence is lacking comparing nusinersen with risdiplam or onasemnogene abeparvovec, two other standard treatments.Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics.