Spinraza
30 March 2026: The FDA approved a new High Dose Regimen for Spinraza (50 mg loading × 2; 28 mg maintenance every 4 months) based on the DEVOTE phase 2/3 study. The original Low Dose Regimen (12 mg loading × 4; 12 mg maintenance every 4 months) — supported by more than a decade of clinical data — remains an approved option. Both regimens are detailed in this monograph.
Indications
Nusinersen was the first disease-modifying therapy approved for spinal muscular atrophy (SMA), a severe autosomal-recessive neuromuscular disorder caused by deletion or loss-of-function variants in the survival motor neuron 1 (SMN1) gene. Patients with SMA produce insufficient survival motor neuron (SMN) protein and progressively lose anterior horn cells, leading to muscle weakness, respiratory failure, and historically, death in infancy in the most severe forms (Type 1). Nusinersen is an antisense oligonucleotide that binds an intronic splicing silencer in the SMN2 gene, promoting inclusion of exon 7 and increasing production of full-length, functional SMN protein from the back-up SMN2 gene that all SMA patients retain in variable copy numbers. Nusinersen is delivered intrathecally to achieve direct exposure of motor neurons in the spinal cord and brainstem, where systemic delivery would not penetrate the blood-brain barrier.
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Spinal muscular atrophy (SMA) — including infantile-onset (Type 1), later-onset (Types 2 and 3), and presymptomatic disease | Pediatric and adult patients (no age restriction in FDA labelling) | Monotherapy (chronic, every-4-month maintenance dosing) | FDA & EMA Approved |
Effectiveness has been demonstrated across the SMA spectrum. The pivotal infantile-onset trial (ENDEAR; Type 1, ≤7 months at screening, two SMN2 copies; n=121 randomised 2:1 to nusinersen vs sham) showed a motor-milestone responder rate of 51% with nusinersen versus 0% with sham control (P<0.001 at the final analysis) and a statistically significant 47% relative reduction in the risk of death or permanent ventilation (HR 0.53, 95% CI 0.32–0.89, P=0.005), as well as a 63% reduction in the risk of death alone (HR 0.37, 95% CI 0.18–0.77, P=0.004). The pivotal later-onset trial (CHERISH; Types 2 and 3, ages 2–12 years at screening with symptom onset after 6 months; n=126) demonstrated a clinically meaningful improvement in motor function on the Hammersmith Functional Motor Scale–Expanded (HFMSE) — least-squares mean difference of 5.9 points (95% CI 3.7–8.1) at the prespecified interim analysis (P<0.001) and 4.0 points at the final analysis, with 57% of nusinersen-treated children versus 26% of sham-treated children achieving a clinically meaningful ≥3-point HFMSE increase. The presymptomatic NURTURE study in genetically diagnosed infants ≤6 weeks of age has shown that early initiation can result in achievement of age-appropriate motor milestones and survival exceeding what would be predicted by SMN2 copy number — establishing the clinical principle that earlier treatment is better.
The High Dose Regimen approval (March 2026) was based on the DEVOTE phase 2/3 study, in which the High Dose Regimen demonstrated a statistically significant 67% reduction in the risk of death or permanent ventilation versus a matched historical sham control (P=0.0006) and a 15.1-point CHOP-INTEND improvement at Day 183 in treatment-naïve infantile-onset SMA. Nusinersen is one of three approved disease-modifying therapies for SMA (alongside onasemnogene abeparvovec gene therapy and risdiplam oral SMN2 splicing modifier); choice between them depends on age, weight, anatomical access for lumbar puncture, AAV9 antibody status, prior therapies, and patient/family preference.
Combination or sequential therapy with risdiplam or onasemnogene abeparvovec — increasingly described in real-world cohorts in patients with suboptimal response. Evidence quality: low–moderate (observational; no head-to-head randomised data). Combination strategies should be specialist-led and discussed within multidisciplinary SMA care teams.
Adults with later-onset SMA beyond the age range of pivotal trials — extensive real-world experience supports use, but pivotal Biogen-sponsored trials did not include adults. Evidence quality: moderate based on prospective adult cohorts.
Off-label use should follow shared decision-making and ideally be coordinated through neuromuscular specialists experienced in SMA care.
Dosing
Two dosing regimens are approved by the FDA: the original Low Dose Regimen (12 mg) supported by more than a decade of clinical data and the new High Dose Regimen (50 mg loading / 28 mg maintenance) approved in March 2026 based on the DEVOTE study. Both regimens deliver maintenance doses every 4 months (3 times per year) via intrathecal bolus injection over 1 to 3 minutes by, or under the direction of, healthcare professionals experienced in performing lumbar punctures. Treatment is administered in a designated centre with appropriate sedation and imaging support where required. Tablets are not available — nusinersen is supplied only as a clear, colourless solution in single-dose vials that should be allowed to warm to room temperature before administration. A volume of cerebrospinal fluid approximately equivalent to the volume of the dose (5 mL) should be removed prior to each injection.
Low Dose Regimen (12 mg)
| Clinical Scenario | Loading Phase | Maintenance Phase | Maximum / Frequency | Notes |
|---|---|---|---|---|
| SMA — all ages and types (treatment-naïve, Low Dose Regimen) | 12 mg (5 mL) × 4 loading doses: first 3 doses at 14-day intervals; 4th dose 30 days after the 3rd | 12 mg (5 mL) once every 4 months | 3 maintenance doses per year; lifelong therapy unless discontinued | Use only the 12 mg/5 mL vial Total of 4 loading + 3 maintenance doses in year 1 |
High Dose Regimen (50 mg loading / 28 mg maintenance)
| Clinical Scenario | Loading Phase | Maintenance Phase | Maximum / Frequency | Notes |
|---|---|---|---|---|
| SMA — treatment-naïve patients (High Dose Regimen) | 50 mg (5 mL) × 2 loading doses, given 14 days apart | 28 mg (5 mL) once every 4 months, starting 4 months after the 2nd loading dose | 3 maintenance doses per year; lifelong therapy unless discontinued | Accelerated loading phase compared with the 12 mg regimen Use 50 mg/5 mL vial for loading and 28 mg/5 mL vial for maintenance |
| Transition from Low Dose to High Dose Regimen | Single 50 mg (5 mL) loading dose given at least 4 months (±14 days) after the last 12 mg maintenance dose | 28 mg (5 mL) once every 4 months, on the patient’s existing schedule | 3 maintenance doses per year; continues lifelong therapy | Patients should resume their established 4-month dosing intervals after the single transition loading dose |
Missed Doses
- If a loading or maintenance dose is delayed or missed: administer as soon as possible. Per the FDA prescribing information, the Low Dose Regimen should be restarted with 12 mg loading doses if the gap is sufficient to compromise expected steady-state concentrations.
- For the High Dose Regimen: follow the manufacturer’s restart guidance in the prescribing information; specialist input is recommended for any significant deviation from the protocol.
- Missed doses are common in adolescents and adults due to scheduling, anatomy, or insurance issues — proactively schedule the next dose at the time of administration.
Important Preparation and Administration Instructions
- Allow the vial to warm to room temperature before administration. Do not use other warming methods.
- Inspect for particulate matter and discoloration; the solution should be clear and colourless.
- Withdraw the dose into a syringe and discard any unused portion.
- Consider sedation as indicated by the patient’s clinical status. In patients with extensive spinal instrumentation or rotoscoliosis, image-guided alternative approaches (transforaminal, cervical, or cone-beam CT-guided) may be necessary.
- Remove a volume of cerebrospinal fluid approximately equal to the volume of the dose (5 mL) before administration.
- Administer as an intrathecal bolus over 1 to 3 minutes using a spinal anaesthesia needle. Do not inject into areas with infection or inflammation of the overlying skin.
- Conduct the required laboratory tests (platelet count, coagulation studies, quantitative spot urine protein) at baseline and prior to each dose.
Special Populations
- Renal impairment: nusinersen is excreted via the kidney, but no dose adjustment is specified in labelling. Monitor for proteinuria before each dose. Use cautiously in significant renal impairment given the warning for ASO-associated renal toxicity.
- Hepatic impairment: not specifically studied; minimal hepatic metabolism is expected.
- Paediatric: approved without age restriction in the FDA label. Pivotal trials enrolled patients from 3 days to 16 years of age at first dose. The presymptomatic NURTURE study enrolled infants ≤6 weeks of age with genetically confirmed SMA. The High Dose Regimen safety database includes patients approximately 14 days to 65 years of age at first dose.
- Adults: pivotal Biogen-sponsored trials did not include sufficient adult numbers; real-world cohorts in adults up to age 71 years support efficacy and tolerability.
- Pregnancy: no adequate human data. Animal data suggest possible fetal harm. Discuss benefit/risk on an individual basis. There is a Spinraza pregnancy registry; report exposed pregnancies to Biogen.
- Lactation: no human data on excretion in human milk. Decision to continue or hold therapy should weigh maternal benefit against unknown infant risk.
The most important non-dosing factor in nusinersen outcomes is timing of initiation relative to motor neuron loss. SMA produces irreversible loss of anterior horn cells; nusinersen prevents further loss but does not regenerate motor neurons that have already died. Presymptomatic treatment (informed by newborn screening, now universal in the US and many other countries) gives the highest chance of normal motor development; symptomatic infants treated earliest in disease course in ENDEAR had the greatest milestone gains. Newborn screening, expanded SMA carrier testing, and rapid access to disease-modifying therapy should be priorities in any SMA care pathway.
Pharmacology
Mechanism of Action
Nusinersen is a 2′-O-(2-methoxyethyl) phosphorothioate antisense oligonucleotide that binds to a specific intronic splicing silencer site (ISS-N1) on the SMN2 pre-messenger RNA, displacing splicing factors that would otherwise promote the exclusion of exon 7. As a result, SMN2 transcripts include exon 7 and are translated into full-length, functional SMN protein rather than the truncated, rapidly degraded protein normally produced by SMN2. SMA patients all carry homozygous loss of SMN1 but retain at least one copy of SMN2; nusinersen exploits this back-up gene to restore SMN protein in motor neurons, slowing or arresting motor neuron degeneration in the spinal cord and brainstem.
Because oligonucleotides do not cross the blood-brain barrier, nusinersen must be delivered intrathecally to reach motor neurons. After intrathecal injection, nusinersen distributes through cerebrospinal fluid throughout the central nervous system and into peripheral tissues including skeletal muscle, liver, and kidney. Long tissue half-lives (months) underpin the every-4-month maintenance schedule. Nusinersen is not metabolised by cytochrome P450 enzymes and is not a substrate, inhibitor, or inducer of CYP isoforms or major drug transporters at clinically relevant concentrations.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Administered intrathecally; trough plasma concentrations are relatively low compared with trough CSF concentrations | Direct CSF delivery is required because oligonucleotides do not cross the blood-brain barrier; systemic exposure is minimal but not zero, which contributes to peripheral organ distribution and toxicity considerations |
| Distribution | Distributed within CNS and peripheral tissues including skeletal muscle, liver, and kidney | Wide tissue distribution explains the peripheral safety signals (renal toxicity warning, thrombocytopenia warning) shared with the antisense oligonucleotide drug class |
| Metabolism | Metabolised by 3′- and 5′-exonuclease–mediated hydrolysis to chain-shortened metabolites. Not a substrate, inhibitor, or inducer of cytochrome P450 enzymes; no significant pharmacokinetic drug-drug interactions identified | Few traditional drug-drug interactions; the practical issues centre on additive toxicity (anticoagulants, nephrotoxic drugs) and on the procedure itself (lumbar puncture) |
| Elimination | Mean terminal elimination half-life approximately 135–177 days in CSF and 63–87 days in plasma. Primary route of elimination is urinary excretion of nusinersen and its chain-shortened metabolites; only ~0.5% of an administered dose is recovered in urine within 24 hours | The very long CSF half-life supports the every-4-month maintenance schedule. Renal monitoring (proteinuria) is required because of urinary excretion and the class warning for ASO-associated renal toxicity |
Cardiac electrophysiology has been examined: across sham-controlled studies in 247 patients with SMA receiving the Low Dose Regimen, only 4 (2.4%) had QTcF values >500 ms or change from baseline >60 ms, with no signal for delayed ventricular repolarisation events versus sham control. Immunogenicity has been characterised in the Low Dose Regimen and in the High Dose Regimen (the latter evaluated in 117 patients with post-baseline plasma samples for anti-drug antibodies, of whom 11 [9%] developed treatment-emergent ADAs); ADAs had no observed effect on clinical function, plasma neurofilament light, or the incidence of hypersensitivity, anaphylactic reaction, or angio-oedema.
Side Effects
The safety profile of nusinersen is shaped by three factors: the underlying SMA disease in the population studied (which contributes high rates of pneumonia, atelectasis, and constipation in infantile-onset cohorts and post-procedural symptoms in older children and adults); the antisense oligonucleotide drug class (thrombocytopenia, coagulation abnormalities, renal toxicity); and the lumbar-puncture delivery route (post-LP syndrome, headache, back pain, rare meningitis, hydrocephalus). Frequencies below are drawn from FDA prescribing information adverse-reaction tables for ENDEAR (Study 1, infantile-onset, Low Dose Regimen) and CHERISH (Study 2, later-onset, Low Dose Regimen), the integrated safety analysis of seven nusinersen clinical trials, and the DEVOTE study supporting the High Dose Regimen.
| Adverse Effect | Nusinersen vs Sham | Clinical Note |
|---|---|---|
| Lower respiratory tract infection (composite term per FDA PI: includes pneumonia, bronchiolitis, RSV bronchiolitis, lower respiratory tract infection, bronchitis, lung infection, and related diagnoses) | 55% (44/80) vs 37% (15/41) | Reflects both class effect and the underlying respiratory vulnerability of infantile-onset SMA. Manage as for any paediatric LRTI; admission and respiratory support as required |
| Constipation | 35% (28/80); ≥5% more frequent than sham per FDA PI | Common in SMA Type 1 due to bulbar weakness and reduced bowel motility. Routine bowel regimen (osmotic laxative ± stimulant) is appropriate |
| Atelectasis (reported as serious adverse reaction) | 18% (14/80) vs 10% (4/41) | More common in nusinersen-treated patients but largely reflects underlying disease severity. Aggressive airway clearance and respiratory physiotherapy are key |
| Adverse Effect | Nusinersen vs Sham | Clinical Note |
|---|---|---|
| Pyrexia (fever) | 43% vs 36% | Often peri-procedural; usually self-limited. Antipyretics as needed |
| Headache (includes post-lumbar-puncture headache) | 29% vs 7% | Use atraumatic (pencil-point) needles when possible to reduce risk; standard hydration, caffeine, and analgesia for management |
| Vomiting | 29% vs 12% | Often peri-procedural; consider sedation/positioning factors. Standard antiemetics where indicated |
| Back pain | 25%; ≥5% more frequent than sham per FDA PI | Procedure-related muscular and ligamentous pain. NSAIDs or acetaminophen typically sufficient; consider procedural technique review if recurrent |
| Adverse events possibly related to study drug (CHERISH) | 29% vs 10% | Per Mercuri 2018 NEJM. Most events were attributed to SMA disease, common population events, or the lumbar puncture procedure |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Post-lumbar-puncture syndrome | Reported in FDA PI; more common in older children and adults than infants | Position-dependent headache classically improving when supine; rarely requires blood patch. Common procedural sequela of intrathecal administration |
| Mild thrombocytopenia (lab finding: platelet count below the lower limit of normal at any time after baseline) | 16% (24/146) vs 14% (10/72) sham, pooled across infantile- and later-onset Low Dose Regimen studies | Lab finding from pooled sham-controlled studies. Pre-dose platelet count and coagulation testing are required at baseline and before each dose |
| Elevated urine protein | 58% (71/123) vs 34% (22/65) sham, pooled across infantile- and later-onset Low Dose Regimen studies | Common lab finding consistent with the antisense oligonucleotide class effect. Quantitative spot urine protein at baseline and before each dose. For values >0.2 g/L, repeat testing and further evaluation |
| Coagulation abnormalities (class warning) | FDA PI describes as a class effect; specific frequencies not tabulated | Coagulation laboratory testing (PT, aPTT) is required at baseline and before each dose. Investigate clinically significant prolongation before proceeding with intrathecal administration |
| Adverse Effect | Comment | Clinical Note |
|---|---|---|
| Pneumonia | ≥10% of high-dose-treated infants | Consistent with infantile-onset SMA respiratory vulnerability |
| COVID-19 | ≥10% — represents a population/era effect | Per FDA PI: COVID-19 was not described at the time of ENDEAR (the source of the historical sham control), so the imbalance partially reflects the pandemic-era enrolment of DEVOTE rather than a drug-attributable effect |
| Pneumonia, aspiration | ≥10% — reflects underlying disease | Bulbar weakness in infantile-onset SMA predisposes to aspiration. Aggressive airway clearance and feeding evaluations |
| Malnutrition | ≥10% — reflects underlying disease | Feeding difficulties common in SMA Type 1; multidisciplinary nutritional support is essential |
| Decreases in platelet counts | Observed in High Dose Regimen recipients per FDA PI | Pre-dose platelet count monitoring applies to both regimens |
Per FDA labelling, the safety profile of the High Dose Regimen is generally consistent with the well-characterised safety of the Low Dose Regimen.
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Acute severe thrombocytopenia (class effect of antisense oligonucleotides) | Rare. In CHERISH (Study 2), 2 nusinersen-treated patients developed platelet counts <50,000 cells/µL, with a lowest level of 10,000 cells/µL on study day 28 | Variable; can occur after any dose | Hold further dosing until platelet count recovers; investigate alternative aetiologies; consult haematology if persistent |
| Renal toxicity (including potentially fatal glomerulonephritis — class effect of ASOs) | Rare; potentially fatal cases reported with other antisense oligonucleotides. Asymptomatic proteinuria observed in 58% of treated patients | Variable | Quantitative spot urine protein before each dose. For values >0.2 g/L, repeat testing and consider further nephrology evaluation. Hold further dosing if persistent or worsening proteinuria |
| Hydrocephalus (communicating; not related to meningitis or bleeding) | Rare; identified in post-marketing reports | Variable | Per FDA PI: some patients have been managed with implantation of a ventriculoperitoneal shunt. Investigate any new or progressive neurological signs of raised intracranial pressure (vomiting, irritability, head circumference change, papilloedema); consult neurosurgery |
| Aseptic meningitis and arachnoiditis | Rare; identified in post-marketing reports | Hours to days post-injection | Investigate fever, neck stiffness, photophobia, severe headache; differentiate from infective meningitis. Manage supportively; involve neurology |
| Serious infections related to lumbar puncture (including bacterial meningitis) | Rare; identified in post-marketing reports | Days to weeks post-injection | Strict aseptic technique. Investigate fever and meningeal signs urgently. Standard CSF analysis and empirical broad-spectrum antibiotics for suspected bacterial meningitis |
| Hypersensitivity reactions (angioedema, urticaria, rash) | Rare; identified in post-marketing reports | Minutes to hours post-injection | Manage acutely with antihistamines, corticosteroids, and adrenaline as indicated. Reconsider therapy after specialist input |
| Delayed-onset rash (distinct from acute hypersensitivity) | Rare. Per FDA PI: 2 patients developed painless red macular skin lesions 8 and 10 months after starting nusinersen, respectively; both continued therapy with spontaneous resolution | Months after initiation (8–10 months in described cases) | Document carefully; refer to dermatology if extensive or atypical. Specialist input regarding continuation. In described cases, treatment was continued with spontaneous resolution |
| Severe hyponatremia | Reported in one infant in an open-label study, requiring 14 months of salt supplementation | Variable | Investigate electrolytes if there are clinical signs (lethargy, seizures, vomiting). Manage acutely; consult nephrology/endocrinology if persistent |
| Bleeding complications related to coagulation abnormalities | Rare | Variable | Required platelet count and coagulation testing before every dose. Investigate any bleeding promptly. Use atraumatic spinal needles to reduce procedural bleeding risk |
| Spinal/epidural haematoma (procedural risk) | Rare | Hours to days post-injection | Avoid procedure if platelets <50,000 cells/µL, abnormal coagulation, or therapeutic anticoagulation; investigate new back pain with weakness, sensory change, or bladder/bowel dysfunction urgently with MRI |
| Reduction in growth (height) when administered to infants | Per FDA PI: nusinersen may cause a reduction in growth as measured by height when administered to infants, as suggested by observations from the controlled study. Reversibility with cessation is unknown | Detected on growth-chart monitoring during ongoing therapy | Monitor height and growth velocity at each visit in infants; involve paediatric endocrinology if significant deviation from growth curve |
| Reason for Therapy Interruption / Discontinuation | Incidence | Context |
|---|---|---|
| Difficulty with intrathecal access (extensive scoliosis, spinal instrumentation) | Variable; not formally quantified in pivotal trials | Common practical issue, particularly in older patients with later-onset SMA. Image-guided alternative approaches (transforaminal, cervical, cone-beam CT) often resolve access |
| Persistent severe proteinuria or thrombocytopenia | Rare | Hold further dosing until investigation completed; specialist input required |
| Switch to alternative DMT (risdiplam oral, onasemnogene abeparvovec gene therapy) | Variable; institution-dependent | Patient/family preference, access concerns, or perceived suboptimal response. Specialist neuromuscular team should coordinate transitions |
| Recurrent or severe post-LP syndrome | Uncommon — rarely necessitates discontinuation | Usually managed with technique optimisation, hydration, and analgesia |
| Pregnancy | Variable | Pregnancy registry available; benefit/risk assessment with the patient and the SMA care team |
Every dose of nusinersen requires three baseline laboratory tests: platelet count, coagulation testing (PT/aPTT), and quantitative spot urine protein (preferably first-morning specimen). Skipping these tests is the most common protocol violation and the most common preventable cause of complications. For urinary protein concentration >0.2 g/L, repeat testing and consider further evaluation before proceeding. For platelet count <50,000 cells/µL or significant coagulopathy, defer the procedure and investigate. These checks take minutes and prevent serious complications.
Drug Interactions
Nusinersen has minimal traditional pharmacokinetic drug-drug interaction potential: it is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes; it is metabolised by exonuclease hydrolysis rather than hepatic enzymes; and systemic exposure after intrathecal dosing is low. The clinically relevant interactions therefore relate primarily to (1) additive toxicity with antiplatelet, anticoagulant, or nephrotoxic agents that compound the class warnings of thrombocytopenia and renal toxicity; (2) procedural considerations with anticoagulants and antiplatelet drugs around the time of lumbar puncture; and (3) general procedural considerations with sedatives and anaesthetics in patients with SMA-related respiratory and bulbar weakness. There are no documented drug-drug interactions with the other approved SMA therapies (risdiplam, onasemnogene abeparvovec), but combination use is off-label and specialist-directed.
Monitoring
Monitoring centres on three drug-class warnings (thrombocytopenia, coagulation abnormalities, renal toxicity), procedure-related risks (bleeding, infection, post-LP syndrome), the labelled growth-reduction warning in infants, and ongoing assessment of efficacy through standardised motor function measures. Pre-dose laboratory testing is mandated before every dose, both loading and maintenance.
-
Platelet count
Baseline; before every loading and maintenance dose
Routine Mandatory pre-dose test. Investigate any value below the lower limit of normal; defer the procedure if <50,000 cells/µL or with a sharply falling trend, and consult haematology if persistent. -
Coagulation testing (PT, aPTT)
Baseline; before every loading and maintenance dose
Routine Mandatory pre-dose test. Investigate any clinically significant prolongation before proceeding with intrathecal administration. Note that coagulation parameters can be abnormal in immobilised SMA patients. -
Quantitative spot urine protein
Baseline; before every dose (preferably first-morning specimen)
Routine Mandatory pre-dose test. For values >0.2 g/L, repeat testing and consider further nephrology evaluation. Persistent or worsening proteinuria may warrant treatment interruption. -
Pregnancy test
Before initiation in patients of reproductive potential; periodically as clinically indicated
Routine Discuss benefit/risk if pregnancy is planned or confirmed. Report exposed pregnancies to the manufacturer’s pregnancy registry. -
Motor function assessments
Baseline and at regular intervals (typically every 6 months)
Routine Use age- and ability-appropriate scales: CHOP-INTEND for non-sitting infants; Hammersmith Infant Neurological Exam (HINE Section 2) for infants; Hammersmith Functional Motor Scale–Expanded (HFMSE) for sitters; Revised Upper Limb Module (RULM) for upper-limb function; 6-Minute Walk Test (6MWT) for ambulatory patients. Establish individualised treatment goals. -
Pulmonary function
Periodically; every 6–12 months in stable patients; more frequently in symptomatic infants
Routine Assess respiratory muscle strength, sleep-disordered breathing, and need for non-invasive ventilation. Coordinate with multidisciplinary SMA team. -
Growth (height, weight, head circumference)
Every visit in infants and young children
Routine FDA labelling warns of possible reduction in height growth in infants treated with nusinersen. Plot on age-appropriate growth charts and investigate significant deviation from baseline curves; involve paediatric endocrinology if persistent. -
Spinal imaging / orthopaedic review
Periodically based on age and skeletal maturity
Routine Monitor for scoliosis (common in SMA Type 2). Pre-procedure planning may require updated imaging if anatomy changes; alternative LP approaches (cone-beam CT-guided, transforaminal) may become necessary. -
Symptom review post-LP
After every dose; safety-net for delayed complications
Routine Specifically ask about post-LP headache, back pain, fever, neck stiffness (meningitis), new neurological deficits (haematoma), and unexpected bleeding. Counsel families on what symptoms to report. -
Neurological examination for hydrocephalus signs
At each visit and prompted by parental concerns
Trigger-based In infants, monitor head circumference and fontanelle; in older children and adults, assess for headache, vomiting, vision changes, gait disturbance. Investigate with imaging if suspected. -
Renal function (serum creatinine, eGFR)
If proteinuria is detected or other clinical concern
Trigger-based Although not mandated by labelling, evaluate renal function if there is significant proteinuria, hypertension, oedema, or any clinical concern for glomerular disease. -
CSF analysis
If suspicion of meningitis, arachnoiditis, or hydrocephalus
Trigger-based Standard workup for fever with meningeal signs after intrathecal injection. Hold further nusinersen until investigation is complete.
Contraindications & Cautions
Notably, the FDA prescribing information for nusinersen does not list any absolute contraindications in Section 4. However, several practical contraindications relate to the intrathecal route of administration and the antisense oligonucleotide class effects, which are reflected in widely accepted clinical practice.
Practical Contraindications (Procedure-Specific)
- Active infection at the planned puncture site — defer the procedure; use an alternative entry level or postpone until resolved.
- Significant uncorrected coagulopathy or therapeutic anticoagulation that cannot be safely held — proceed only after coagulation parameters are addressed in line with neuraxial procedure guidelines.
- Severe thrombocytopenia (platelet count below local procedural threshold, often <50,000 cells/µL) — defer until investigated and corrected.
- Untreated raised intracranial pressure — investigate with imaging before lumbar puncture if clinical suspicion (papilloedema, focal neurological signs, severe headache).
Relative Contraindications (Specialist Input Recommended)
- Significant pre-existing renal disease, especially active glomerular disease — class warning for ASO-associated renal toxicity.
- Extensive spinal instrumentation, severe scoliosis, or anatomical distortion preventing standard interlaminar access — evaluate alternative approaches (transforaminal, cervical, cone-beam CT-guided) with interventional radiology or anaesthesia input.
- Recent or active CNS infection — defer until resolved.
- Pregnancy — limited human data; use only when potential benefit justifies potential risk, with informed consent and pregnancy registry enrolment.
- Significant immune compromise requiring careful infection-control planning around the procedure.
Use with Caution
- Patients on chronic antiplatelet or anticoagulant therapy — coordinate timing of holds with the prescribing team.
- Patients with bulbar weakness or significant respiratory compromise — anaesthesia input for sedation; ensure ventilatory support is available.
- Patients with significant pre-existing thrombocytopenia or proteinuria — establish baseline trends before starting; involve haematology or nephrology if values are borderline.
- Patients who have received another SMA disease-modifying therapy — multidisciplinary discussion to clarify rationale and define monitoring strategy.
- Lactation — no human data; benefit/risk discussion required.
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia, have been observed after administration of some antisense oligonucleotides. Patients may be at increased risk of bleeding complications. In sham-controlled studies of patients with infantile- and later-onset SMA, 24 of 146 (16%) nusinersen-treated patients with high, normal, or unknown baseline platelet count developed a platelet level below the lower limit of normal versus 10 of 72 (14%) sham-controlled patients. Two nusinersen-treated patients in CHERISH developed platelet counts <50,000 cells/µL (lowest 10,000 cells/µL on day 28). Decreases in platelet counts have also been observed in patients receiving the High Dose Regimen. Obtain a platelet count and coagulation testing at baseline and prior to each dose and as clinically needed.
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Nusinersen is present in and excreted by the kidney. In sham-controlled studies of patients with infantile- and later-onset SMA, 71 of 123 (58%) nusinersen-treated patients had elevated urine protein versus 22 of 65 (34%) sham-controlled patients. Conduct quantitative spot urine protein testing (preferably first-morning specimen) at baseline and prior to each dose. For urinary protein concentration >0.2 g/L, consider repeat testing and further evaluation.
Per FDA labelling, nusinersen may cause a reduction in growth as measured by height when administered to infants, as suggested by observations from the controlled study. It is unknown whether any effect of nusinersen on growth would be reversible with cessation of treatment. Monitor growth at each visit in infants and involve paediatric endocrinology if significant deviation from age-appropriate growth curves is detected.
Post-lumbar-puncture syndrome has been observed after administration of nusinersen. Communicating hydrocephalus not related to meningitis or bleeding has been reported in the post-marketing setting; some patients have been managed with implantation of a ventriculoperitoneal shunt. Aseptic meningitis, hypersensitivity reactions (angioedema, urticaria, rash), and arachnoiditis have also been reported. Serious infections associated with lumbar puncture, such as bacterial meningitis, have been reported. Cases of rash were reported in patients treated with nusinersen: per the FDA prescribing information, one patient developed painless red macular lesions on the forearm, leg, and foot 8 months after starting nusinersen (which ulcerated and scabbed within 4 weeks and resolved over several months), and a second patient developed red macular skin lesions on the cheek and hand 10 months after the start of treatment (which resolved over 3 months); both patients continued therapy with spontaneous resolution. Severe hyponatremia requiring 14 months of salt supplementation was reported in one infant with symptomatic SMA in an open-label study. As with all oligonucleotides, there is potential for immunogenicity, although clinical implications appear minor.
Patient Counselling
Purpose of Therapy
Spinraza is a medicine that treats spinal muscular atrophy (SMA) by helping the body make more of a protein (called SMN) that motor nerve cells need to survive and work properly. It does not cure SMA but slows or stops the loss of motor function and, when started early enough, can allow normal or near-normal motor development. The medicine is given as an injection into the fluid surrounding the spinal cord (intrathecal injection or “lumbar puncture”), because this is the only way to reach the motor nerves directly. Most patients receive 4 loading doses (or 2 with the new High Dose Regimen) followed by maintenance doses every 4 months — about 3 times a year — for life.
How It Is Given
Each dose is given by a healthcare professional experienced in lumbar puncture, typically in a designated treatment centre. The procedure usually takes 1 to 3 minutes for the actual injection but the whole appointment may last several hours including preparation, the procedure, and recovery. Children may need sedation; adults may have it done with local anaesthetic alone. Before each appointment, blood tests (platelets and coagulation) and a urine test (for protein) are required — these can usually be drawn the same day. After the injection, you will need to lie flat for a short period and then can usually go home the same day.
Sources
- Biogen. SPINRAZA (nusinersen) injection — Full Prescribing Information (current version reflecting 30 March 2026 High Dose Regimen approval). https://www.spinraza.com/content/dam/commercial/spinraza/caregiver/en_us/pdf/spinraza-prescribing-information.pdf Primary US labelling; authoritative source for indications, both Low Dose and High Dose regimens, warnings (thrombocytopenia, coagulation, renal toxicity, growth reduction in infants), monitoring, adverse-reaction tables, and the specific delayed-onset rash observations.
- US Food and Drug Administration. SPINRAZA (nusinersen) — 2026 Approved Labelling, NDA 209531 supplement s016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/209531s016lbl.pdf FDA-approved labelling supplement following the High Dose Regimen approval; details DEVOTE/Study 4 efficacy results (67% reduction in death/permanent ventilation; 15.1-point CHOP-INTEND improvement) and immunogenicity data (9% ADAs in 117 evaluable High Dose Regimen patients).
- National Library of Medicine. SPINRAZA — DailyMed Drug Label. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd70cd5f-b0fc-4ba4-a5ea-89a34778bd94 Continuously updated repository of the latest FDA-approved labelling text, reflecting the March 2026 High Dose Regimen approval.
- European Medicines Agency. Spinraza — EPAR Product Information. https://www.ema.europa.eu/en/documents/product-information/spinraza-epar-product-information_en.pdf EU labelling including the 50/28 mg dosing regimen; complementary source for ADA and immunogenicity findings across both regimens.
- Biogen press release. FDA Approves New High Dose Regimen of SPINRAZA (nusinersen) for Spinal Muscular Atrophy. 30 March 2026. https://investors.biogen.com/news-releases/news-release-details/fda-approves-new-high-dose-regimen-spinrazar-nusinersen-spinal Announcement of the High Dose Regimen approval; summarises the dosing schedule, transition guidance from Low Dose, and the supporting DEVOTE study design.
- Finkel RS, Mercuri E, Darras BT, et al; for the ENDEAR Study Group. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377(18):1723–1732. https://doi.org/10.1056/NEJMoa1702752 ENDEAR pivotal phase 3 trial in symptomatic infantile-onset SMA (n=121, randomised 2:1); primary source for motor milestone responder rate (51% vs 0% sham) and 47% relative reduction in death or permanent ventilation (HR 0.53, 95% CI 0.32–0.89, P=0.005).
- Mercuri E, Darras BT, Chiriboga CA, et al; for the CHERISH Study Group. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018;378(7):625–635. https://doi.org/10.1056/NEJMoa1710504 CHERISH pivotal phase 3 trial in later-onset SMA (n=126; ages 2–12 years at screening; symptom onset after 6 months); primary source for HFMSE LSM difference (5.9 points at interim, 4.0 at final), the 57% vs 26% ≥3-point HFMSE responder rate, and AE rates of pyrexia, headache, vomiting, and back pain.
- De Vivo DC, Bertini E, Swoboda KJ, et al; NURTURE Study Group. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the phase 2 NURTURE study. Neuromuscul Disord. 2019;29(11):842–856. https://doi.org/10.1016/j.nmd.2019.09.007 NURTURE study in presymptomatic infants ≤6 weeks of age with genetically confirmed SMA; demonstrates that early initiation can produce age-appropriate motor development.
- Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017–3026. https://doi.org/10.1016/S0140-6736(16)31408-8 Phase 2 open-label dose-escalation study supporting the original 12 mg dosing schedule used in subsequent pivotal trials.
- Darras BT, Farrar MA, Mercuri E, et al. An integrated safety analysis of infants and children with symptomatic spinal muscular atrophy (SMA) treated with nusinersen in seven clinical trials. CNS Drugs. 2019;33(9):919–932. https://doi.org/10.1007/s40263-019-00656-w Integrated safety analysis across seven clinical trials confirming the favourable benefit-risk profile and the most common AEs.
- Acsadi G, Crawford TO, Müller-Felber W, et al. Safety and efficacy of nusinersen in spinal muscular atrophy: the EMBRACE study. Muscle Nerve. 2021;63(5):668–677. https://doi.org/10.1002/mus.27187 EMBRACE study in patients ineligible for ENDEAR or CHERISH; supports broader effectiveness across the SMA spectrum.
- US Food and Drug Administration. Spinraza (nusinersen) — Clinical Pharmacology and Biopharmaceutics Review, NDA 209531. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209531Orig1s000ClinPharmR.pdf FDA review document detailing PK parameters: CSF half-life 135–177 days, plasma half-life 63–87 days, exonuclease metabolism, urinary excretion, no CYP-based interactions.
- Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28(2):103–115. https://doi.org/10.1016/j.nmd.2017.11.005 SMA Standards of Care 2018 — Part 1; establishes the multidisciplinary care framework into which nusinersen is integrated.
- Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord. 2018;28(3):197–207. https://doi.org/10.1016/j.nmd.2017.11.004 SMA Standards of Care 2018 — Part 2; informs vaccination, RSV prophylaxis, and supportive care recommendations.