Spinraza: Uses, Dosage & Side Effects

What Is Spinraza and What Is It Used For?

Spinraza contains the active substance nusinersen, which belongs to a class of medicines called antisense oligonucleotides (ASOs). These are short, synthetic strands of modified nucleotides designed to bind to specific sequences of messenger RNA (mRNA) and alter the way genes are expressed. Nusinersen is a 2'-O-methoxyethyl phosphorothioate-modified antisense oligonucleotide, 18 nucleotides in length, specifically engineered to target the survival motor neuron 2 (SMN2) gene pre-mRNA.

Spinraza is used to treat spinal muscular atrophy (SMA), a rare autosomal recessive genetic disease with an estimated incidence of approximately 1 in 6,000 to 1 in 10,000 live births worldwide. SMA is caused by homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene on chromosome 5q13. The SMN1 gene is the primary gene responsible for producing full-length, functional survival motor neuron (SMN) protein. This protein is essential for the survival and function of motor neurons in the spinal cord — the nerve cells that control voluntary muscle movements including breathing, swallowing, crawling, walking, and head and neck control.

Humans also carry a nearly identical gene called SMN2, which differs from SMN1 by a single nucleotide change in exon 7. This critical difference causes the majority of SMN2 mRNA transcripts to exclude exon 7 during pre-mRNA splicing, resulting in a truncated, unstable, and rapidly degraded SMN protein (known as SMNΔ7). Only approximately 10–15% of SMN2 transcripts naturally produce full-length, functional SMN protein. While this small amount of functional protein explains why patients with more copies of SMN2 tend to have milder disease, it is insufficient to fully compensate for the loss of SMN1 function, and motor neurons progressively degenerate.

Nusinersen works by binding to a specific intronic splicing silencer site called ISS-N1 in intron 7 of the SMN2 pre-mRNA. By blocking this silencer element, nusinersen promotes the inclusion of exon 7 in the mature SMN2 mRNA transcript. This results in a significantly greater proportion of full-length, functional SMN protein being produced from the SMN2 gene. The increased levels of SMN protein help to preserve motor neuron function and survival, slowing or halting the progression of the disease and, in many cases, improving motor function.

SMA is clinically classified into several types based on the age of onset and the highest motor milestone achieved:

• SMA Type 1 (Werdnig-Hoffmann disease): The most severe and common form, accounting for approximately 60% of all SMA cases. Onset occurs before 6 months of age, and affected infants never achieve the ability to sit independently. Without treatment, most children with SMA Type 1 do not survive beyond 2 years of age due to respiratory failure.
• SMA Type 2 (Dubowitz disease): Onset typically occurs between 6 and 18 months of age. Children can sit independently but never achieve the ability to walk unaided. Life expectancy varies but is often reduced.
• SMA Type 3 (Kugelberg-Welander disease): Onset occurs after 18 months of age. Patients achieve the ability to walk independently at some point, although many lose this ability over time. Life expectancy is near normal.
• SMA Type 4: The mildest form with adult onset (typically after age 30). Patients experience mild to moderate muscle weakness. Life expectancy is not significantly affected.

Spinraza was evaluated in two pivotal phase III clinical trials that demonstrated its transformative efficacy:

• ENDEAR (infantile-onset SMA): This randomized, double-blind, sham-controlled trial enrolled 121 infants with SMA Type 1 diagnosed before 7 months of age. After a median treatment duration of approximately 6 months, 51% of Spinraza-treated infants achieved motor milestone improvements (including head control and sitting) compared with 0% of sham-control infants. Event-free survival (defined as being alive and free from permanent ventilation) was significantly higher in the Spinraza group, with a 47% reduction in the risk of death or permanent ventilation.
• CHERISH (later-onset SMA): This randomized, double-blind, sham-controlled trial enrolled 126 children aged 2–12 years with SMA Type 2 or Type 3. After 15 months of treatment, Spinraza-treated children showed a mean improvement of 4.0 points on the Hammersmith Functional Motor Scale – Expanded (HFMSE), compared with a mean decline of 1.9 points in the sham-control group, representing a highly significant treatment difference of 5.9 points.

Spinraza was first approved by the U.S. Food and Drug Administration (FDA) in December 2016 and subsequently by the European Medicines Agency (EMA) in June 2017. It was the first drug ever approved for the treatment of SMA and represented a landmark achievement in the field of neuromuscular medicine. Spinraza is now approved in more than 50 countries worldwide and has been used to treat thousands of patients. Long-term follow-up data from open-label extension studies (SHINE) have demonstrated sustained benefit over more than 5 years of continuous treatment, with many patients maintaining or continuing to improve their motor function.

What Should You Know Before Taking Spinraza?

Contraindications

Spinraza must not be given to patients who are allergic (hypersensitive) to nusinersen or any of the other ingredients in this medicine. The excipients include sodium dihydrogen phosphate dihydrate, disodium phosphate, sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, sodium hydroxide, hydrochloric acid, and water for injections. If you are unsure whether you or your child may be allergic to any of these components, speak with your doctor or nurse before receiving Spinraza.

Warnings and Precautions

There is a risk of side effects occurring after Spinraza is administered via lumbar puncture (see the Dosage and Side Effects sections below). These may include headache, vomiting, and back pain. There may also be difficulties with administering the medicine using this method in very young patients and in those with scoliosis (a twisted and curved spine), which is common in SMA patients. In such cases, imaging guidance (such as fluoroscopy or ultrasound) may be used to assist with the procedure.

Other medicines in the same pharmacological class as Spinraza (antisense oligonucleotides) have been shown to affect blood cells involved in clotting, potentially leading to thrombocytopenia (low platelet count). Before you or your child receives Spinraza, your doctor may decide that blood tests should be taken to check whether blood clotting is functioning properly. This may not be necessary before every dose of Spinraza, but regular monitoring is generally recommended, particularly during the loading phase.

Similarly, other antisense oligonucleotides have been associated with effects on kidney function, including proteinuria (protein in the urine). Before you or your child receives Spinraza, your doctor may decide that urine tests should be taken to check kidney function. Again, this monitoring may not be required before every dose but is generally recommended at baseline and periodically during treatment.

A small number of patients treated with Spinraza have developed hydrocephalus, which is an accumulation of excessive cerebrospinal fluid (CSF) around the brain. Some of these patients required surgical placement of a ventriculoperitoneal (VP) shunt to manage the condition. If you notice any symptoms such as increasing head circumference, decreased consciousness, persistent nausea, vomiting, or headache, or any other symptoms that concern you, contact your or your child's doctor immediately to receive appropriate treatment. The risks and benefits of continuing Spinraza treatment in patients with a VP shunt in place are not currently well established.

Drug Interactions

No formal drug interaction studies have been conducted with nusinersen. Because nusinersen is not metabolized by cytochrome P450 (CYP) enzymes, it is not expected to affect the metabolism of other drugs that are CYP substrates. Nusinersen is metabolized slowly by exonuclease-mediated hydrolysis and has low systemic exposure following intrathecal administration, further reducing the likelihood of clinically significant drug interactions. However, you should always inform your doctor about all medications you or your child are currently taking, have recently taken, or may be planning to take, including over-the-counter medicines and supplements.

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before receiving Spinraza. The use of Spinraza during pregnancy should be avoided as a precaution, as there are limited clinical data on its effects in pregnant women. Animal reproductive studies with nusinersen have not shown evidence of harmful effects on embryo-fetal development, fertility, or postnatal development at clinically relevant doses. However, as a general precaution, the potential risks and benefits should be carefully considered by the treating physician.

It is not known whether nusinersen or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. The decision whether to discontinue breastfeeding or to discontinue Spinraza therapy should be made in consultation with your doctor, taking into account the benefit of breastfeeding for the child and the benefit of Spinraza therapy for the mother.

Effects on Driving and Use of Machines

Spinraza has no or negligible influence on the ability to drive or use machines. However, given that Spinraza treats a condition characterized by muscle weakness, the underlying disease itself may affect these abilities. Patients should be assessed individually regarding their capacity to drive or operate machinery based on their overall clinical status.

How Does Spinraza Interact with Other Drugs?

Nusinersen is an antisense oligonucleotide administered directly into the cerebrospinal fluid via intrathecal injection. Due to its unique route of administration and mechanism of metabolism (exonuclease-mediated hydrolysis rather than hepatic CYP450 metabolism), clinically significant pharmacokinetic drug interactions are not expected. Systemic exposure to nusinersen following intrathecal administration is low, with plasma concentrations representing a small fraction of the concentrations achieved in the cerebrospinal fluid.

Despite the favorable interaction profile, healthcare providers should exercise caution in several specific scenarios. Although no formal interaction studies have been performed, the following theoretical considerations apply based on the pharmacology of antisense oligonucleotides as a class:

It is important to note that the interactions listed above are primarily theoretical and based on class-effect considerations rather than documented clinical interactions with nusinersen specifically. Nonetheless, a proactive approach to monitoring is recommended, especially in patients who are receiving multiple medications. Always provide your healthcare team with a complete and current list of all prescription drugs, over-the-counter medications, vitamins, herbal supplements, and any other products you are taking.

What Is the Correct Dosage of Spinraza?

Spinraza is administered exclusively by healthcare professionals experienced in performing lumbar punctures. Unlike many other medications, the dose of Spinraza does not vary based on age, body weight, or the type or severity of SMA. All patients receive the same fixed dose of 12 mg (5 mL of solution) for each intrathecal injection. The medication is supplied as a clear, colorless solution in a single-use vial that must not be diluted or mixed with other medications.

Loading Phase

Maintenance Phase

Administration Procedure

Each dose of Spinraza is given as an intrathecal injection, meaning it is injected directly into the space surrounding the spinal cord (the subarachnoid space) via a lumbar puncture. This procedure is performed by a physician experienced in administering intrathecal medications. The injection is delivered as a slow bolus over 1–3 minutes using a spinal anesthesia needle. Before each injection, it is recommended that a volume of cerebrospinal fluid equivalent to the volume of Spinraza to be injected (5 mL) be removed.

Patients may receive sedation, general anesthesia, or local anesthesia prior to the procedure, depending on their age, clinical status, and preference. Very young infants and patients with significant scoliosis may require imaging guidance (such as fluoroscopy or ultrasound) to facilitate accurate needle placement. The procedure is typically performed in a hospital or specialized clinic setting.

Missed Dose

If you or your child misses a scheduled dose of Spinraza, contact your doctor as soon as possible to arrange for the injection to be given at the earliest opportunity. It is important to maintain the dosing schedule as closely as possible to ensure that therapeutic drug concentrations in the cerebrospinal fluid remain adequate. Your doctor will advise on the best timing for subsequent doses after a missed injection.

Overdose

No cases of overdose with Spinraza have been reported in clinical trials or post-marketing experience. Given the controlled clinical setting in which Spinraza is administered by healthcare professionals, the risk of accidental overdose is extremely low. In the event of an inadvertent overdose, the patient should be monitored closely, and supportive care should be provided as clinically indicated. There is no specific antidote for nusinersen overdose.

Duration of Treatment

Your doctor will tell you how long you or your child needs to receive Spinraza. Current clinical evidence supports long-term, ongoing treatment, as discontinuation may lead to gradual decline in the benefits achieved. Do not stop treatment with Spinraza unless your doctor advises you to do so. Open-label extension studies have shown that patients who continue treatment for 5 or more years maintain the motor function gains achieved during the initial treatment period, and many continue to show gradual improvements over time.

What Are the Side Effects of Spinraza?

Like all medicines, Spinraza can cause side effects, although not everybody gets them. It is important to understand that many of the reported adverse events associated with Spinraza treatment are related to the lumbar puncture procedure used for intrathecal administration, rather than to the drug itself. Most of these procedure-related side effects have been reported within 72 hours of the injection and are generally mild to moderate in severity, resolving without specific treatment.

The safety profile of Spinraza has been established through extensive clinical trial data (including the ENDEAR, CHERISH, and NURTURE studies) and more than 8 years of post-marketing surveillance. The overall benefit-risk profile is considered favorable by regulatory authorities worldwide, and the most common adverse effects are manageable with standard clinical care.

In the pivotal ENDEAR trial in infantile-onset SMA, the most frequently reported adverse events in Spinraza-treated patients were respiratory infection (including lower respiratory tract infection and pneumonia), constipation, and signs of teething. These events were largely attributable to the underlying disease and the patient population (young infants with severe SMA) rather than to Spinraza itself, as many of these events occurred at similar rates in the sham-control group.

Post-lumbar puncture syndrome is a recognized complication of any lumbar puncture procedure, not specific to Spinraza. It typically presents as a positional headache that worsens when sitting upright and improves when lying down. This occurs because cerebrospinal fluid leaks through the puncture site in the dura mater. Strategies to minimize this risk include using small-gauge, non-cutting spinal needles and keeping the patient lying flat for a period after the procedure.

Regarding the reported cases of hydrocephalus, this condition has been observed in a small number of patients treated with Spinraza. The relationship between Spinraza treatment and the development of hydrocephalus is not fully understood, and communicating hydrocephalus is also a recognized feature of SMA itself, particularly in patients with more severe disease. Patients and caregivers should be vigilant for signs such as unusual increases in head circumference (in infants), persistent vomiting, altered consciousness, or persistent headache, and report these symptoms to the treating physician immediately.

How Should You Store Spinraza?

Proper storage of Spinraza is essential to ensure the medication remains safe and effective. Because Spinraza is administered in a clinical setting by healthcare professionals, storage is primarily the responsibility of the hospital or clinic pharmacy. However, it is helpful for patients and caregivers to understand the storage requirements.

Spinraza should be stored in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F). The vials must not be frozen at any time. If the solution has been inadvertently frozen, it should not be used. The vials should be kept in the original outer carton to protect from light, as the solution is light-sensitive.

If refrigeration is not available (for example, during transport), Spinraza may be stored in its original carton, protected from light, at a temperature at or below 30 °C (86 °F) for a maximum of 14 days. Unopened vials of Spinraza can be removed from and returned to the refrigerator as needed. However, if the vial is removed from the original carton, the total cumulative time outside the refrigerator must not exceed 30 hours at a temperature not exceeding 25 °C (77 °F).

Each vial of Spinraza is intended for single use in one patient only. Any unused solution remaining in the vial after administration should be discarded. Once the solution has been drawn into a syringe, it must be used within 6 hours; if not used within this timeframe, it must be discarded. Do not use Spinraza after the expiry date stated on the vial and carton.

Keep this medicine out of the sight and reach of children. Unused medicine should not be disposed of via household waste or wastewater. Healthcare professionals will dispose of unused medicine according to local institutional guidelines and applicable regulations.

What Does Spinraza Contain?

Each single-use vial of Spinraza contains nusinersen sodium, equivalent to 12 mg of nusinersen in 5 mL of solution. This corresponds to a concentration of 2.4 mg per mL. Nusinersen sodium is the sodium salt form of the active substance, which facilitates dissolution in the aqueous solution.

The other ingredients (excipients) in Spinraza are:

• Sodium dihydrogen phosphate dihydrate – buffer component to maintain solution pH
• Disodium phosphate – buffer component to maintain solution pH
• Sodium chloride – tonicity agent to match the osmolality of cerebrospinal fluid
• Potassium chloride – electrolyte for physiological compatibility
• Calcium chloride dihydrate – electrolyte for physiological compatibility
• Magnesium chloride hexahydrate – electrolyte for physiological compatibility
• Sodium hydroxide – pH adjustment
• Hydrochloric acid – pH adjustment
• Water for injections – solvent

The formulation is designed to closely match the composition and osmolality of natural cerebrospinal fluid, which is essential for an intrathecally administered medication. This minimizes irritation at the injection site and ensures optimal tolerability.

Spinraza contains less than 1 mmol (23 mg) of sodium per 5 mL vial, meaning it is essentially “sodium-free.” It also contains less than 1 mmol (39 mg) of potassium per 5 mL vial, meaning it is essentially “potassium-free.” These amounts are negligible and can be disregarded from a dietary perspective, even in patients on sodium-restricted diets.

The solution appears as a clear, colorless liquid in a glass vial. Before administration, healthcare professionals must visually inspect the vial for particulate matter or discoloration. If particles are observed or the solution is not clear and colorless, the vial must not be used. Aseptic technique must be employed throughout the preparation and administration process. Spinraza does not require dilution and should not be mixed with other medications. No external filters are needed for administration.