SPINRAZA (nusinersen) is indicated for the treatment of spinal muscular atrophy (SMA) in paediatric and adult patients.
It was originally developed by Ionis Pharmaceuticals, a US-based biotechnology company.
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Ionis Pharmaceuticals transferred the global rights to develop, produce and market SPINRAZA to American biotechnology company Biogen in August 2016.
Spinraza is available as a clear, colourless solution of 12mg/5ml (2.4mg/ml) dosage strength in a single-dose vial for intrathecal injection.
Regulatory approvals for SPINRAZA
Spinraza was first approved by the US Food and Drug Administration (FDA) under priority review in December 2016 and subsequently approved in Europe in June 2017. It was the first approved treatment for SMA in the EU. The drug is currently available in more than 71 countries.
In March 2026, the FDA approved a higher-dose regimen of Spinraza for the treatment of SMA. This higher-dose approach was developed to deliver increased drug exposure during both loading and maintenance periods, offering an additional regimen option intended to address ongoing treatment needs in the SMA community.
For individuals initiating Spinraza therapy, the new regimen provides an accelerated loading phase consisting of two 50mg doses given 14 days apart, followed by 28mg maintenance injections every four months.
Patients already receiving the lower-dose regimen can transition by receiving a single higher-dose loading administration, after which they can continue the 28mg maintenance dosing at four-month intervals, aligned with their existing treatment schedule.
The high-dose Spinraza is also approved in the EU, Switzerland, and Japan.
Spinal muscular atrophy causes and symptoms
SMA is a genetic disorder that affects the part of the nervous system that regulates muscular movement. The disease is caused by the loss of motor neurons in the spinal cord.
The disease can occur in two forms, Type 1 and Type 2. Each form is characterised by distinct features in terms of onset, motor development, and severity.
Both SMA types are caused by mutations in the survival motor neuron 1 (SMN1) gene, resulting in a deficiency of the SMN protein. The severity of the condition is influenced by the presence of a related gene, SMN2, which can produce some functional SMN protein but is less efficient than SMN1.
SMA Type 1 is life-threatening and fatal. The symptoms typically appear within the first six months of life, often evident in the first few weeks.
Infants with SMA Type 1 experience severe muscle weakness and have difficulty achieving motor milestones such as sitting or crawling. Independent sitting is usually not achieved.
Type 2 is less severe but has life-altering forms. Onset occurs later, usually between six and 18 months of age. Children with SMA Type 2 have less severe muscle weakness. While they may acquire some motor skills, such as sitting without support, they generally do not achieve the ability to stand or walk independently.
Spinraza’s mechanism of action
Spinraza is an antisense oligonucleotide (ASO) utilising Ionis Pharmaceuticals’ proprietary antisense technology. ASOs are concise synthetic sequences of nucleotides designed to selectively bind to target ribonucleic acid (RNA), thereby regulating gene expression.
The drug is specifically crafted to address SMA resulting from mutations or deletions in the SMN1 gene on chromosome 5q, leading to a deficiency of the SMN protein. By modifying the splicing of SMN2 pre-mRNA, Spinraza boosts the production of complete SMN protein.
The drug can be administered through intrathecal injection directly into the cerebrospinal fluid around the spinal cord. The targeted approach addresses the degeneration of motor neurons in individuals with SMA, stemming from insufficient levels of SMN protein.
Clinical trials on SPINRAZA
The FDA approval for Spinraza was based on results obtained from the ENDEAR Phase III study.
ENDEAR was a randomised, double-blind, sham-controlled clinical study conducted for 13 months on 121 patients with infantile-onset SMA. The motor milestone response was measured by the Hammersmith Infant Neurological Examination (HINE), which is a neurological exam that helps clinicians identify movement disorders in infants.
Results of the interim analysis showed that infants treated with Spinraza achieved the primary endpoint of motor milestone response compared to those who did not receive treatment. In addition, a smaller percentage of patients (23%) treated with Spinraza died compared to untreated patients (43%). The study also showed that other efficacy endpoints were consistently in favour of infants who were treated with Spinraza.
A second Phase III study, CHERISH, was conducted for 15 months on 126 non-ambulatory patients with later-onset SMA.
In the study, children treated with Spinraza exhibited a substantial and statistically significant enhancement in motor function.
The improvement was clinically meaningful, evident in a treatment difference of 4.9 points in the mean change from baseline to month 15 on the Hammersmith Functional Motor Scale Expanded (HFMSE) score, which is used to evaluate motor function in children with SMA.
Long-term clinical trials on Spinraza
The SHINE open-label extension Phase III study was initiated for patients who took part in the ENDEAR and CHERISH studies. The SHINE study recruited 292 participants and intended to evaluate Spinraza’s long-term safety and tolerability.
Updated SHINE data released in 2020 indicated that Spinraza led to improved motor outcomes or maintained disease stability in toddlers, children and young adults receiving uninterrupted treatment, with some exposed for as long as six and a half years.
Phase II clinical studies EMBRACE and NURTURE were initiated to collect additional data on Spinraza on a smaller subset of patients with infantile or later-onset SMA, who did not meet the age and other criteria of ENDEAR or CHERISH studies.
EMBRACE was a 14‑month, randomised, double-blind, multi-centre trial that evaluated Spinraza in infants and children and included a sham-procedure control.
Interim results from the study showed that a higher share of Spinraza-treated infants and children achieved HINE motor milestone responder status than those who received no treatment. The analysis also reinforced the planned regimen of four loading doses over the first two months, followed by maintenance dosing every four months for patients with infantile-onset and later-onset SMA.
The NURTURE trial, a Phase Ⅱ open-label study, evaluated Spinraza’s long-term efficacy and safety in 25 pre-symptomatic patients with SMA. Recent findings indicate that administering Spinraza early and consistently for a duration of up to 4.8 years has led to remarkable improvements in survival rates.
The NURTURE study has been extended to assess the ongoing efficacy and safety of Spinraza in children aged up to eight years.
The global two-year Phase IV open-label RESPOND clinical trial evaluates clinical outcomes and safety of the Spinraza treatment in infants and toddlers with SMA who have unmet clinical needs after being treated with Zolgensma.
Interim efficacy results showed improvements in motor function in most participants as measured by an increased mean total HINE-2 score from baseline. New data released in 2024 indicated that plasma neurofilament light chain (NfL) concentrations, an objective indicator of axonal damage and neurodegenerative processes, declined in almost every participant who received Spinraza.
Clinical trials on higher dose Spinraza
The FDA approval of the higher-dose regimen of Spinraza was supported by data from the three-part Phase II/III DEVOTE trial that enrolled 139 participants across a range of ages and SMA phenotypes.
Part A examined the safety and tolerability of higher nusinersen doses. Part B evaluated efficacy in a randomised, double-blind setting. Part C investigated the safety and tolerability of switching participants from the 12mg regimen to higher-dose regimens. Findings from Part A supported continued development of higher-dose nusinersen.
In the pivotal Part B cohort, treatment‑naive, symptomatic infants receiving the high‑dose nusinersen regimen showed statistically significant motor function improvement as measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) versus a prespecified matched sham (untreated) group from the ENDEAR study, with a mean difference of 26.19 points. Secondary outcomes also favoured the high dose, with biomarker and efficacy data trending towards benefit over the authorised 12mg dose.
In the open‑label Part C (n=40), participants aged 4–65 years switched from the 12mg regimen to a high‑dose schedule (one 50mg dose four months after the last 12mg dose, then 28mg every four months) after a median of 3.9 years on 12mg.
By day 302, mean motor function gains from baseline were 1.8 points on HFMSE and 1.2 points on Revised Upper Limb Module (RULM), an assessment used to measure upper limb function in SMA patients.
In infants with infantile‑onset SMA treated with the high‑dose Spinraza regimen, the most frequently reported adverse reactions, occurring in at least 10% of patients and at least 5% more often than in a historical matched sham‑control group, were pneumonia, Covid‑19, aspiration pneumonia and malnutrition.
