Qalsody (Tofersen)
Antisense Oligonucleotide for SOD1-Amyotrophic Lateral Sclerosis
Quick Facts About Qalsody
Key Takeaways About Qalsody (Tofersen)
- Qalsody is the first targeted therapy specifically approved for SOD1-ALS, a rare genetic form of motor neuron disease affecting approximately 2% of all ALS patients.
- The drug is administered every 28 days via intrathecal injection (lumbar puncture) by an experienced healthcare professional, following an initial loading phase of three doses at 14-day intervals.
- Clinical trials demonstrated significant reductions in neurofilament light chain (NfL) and CSF SOD1 protein levels, biomarkers associated with nerve damage and disease activity.
- Serious but uncommon side effects include myelitis (spinal cord inflammation), radiculitis (nerve root damage), papilloedema, and aseptic meningitis – patients must be monitored closely.
- Qalsody was approved under exceptional circumstances due to the rarity of SOD1-ALS, with regulatory agencies reviewing emerging data annually to confirm its benefit-risk profile.
What Is Qalsody and What Is It Used For?
Qalsody contains the active substance tofersen, which belongs to a class of medicines called antisense oligonucleotides (ASOs). These are short, synthetic strands of nucleic acid designed to bind to a specific messenger RNA (mRNA) target and trigger its degradation. In the case of tofersen, the target is the mRNA produced by the SOD1 gene, which encodes the superoxide dismutase 1 protein.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that destroys motor neurons – the nerve cells in the brain and spinal cord responsible for sending instructions to muscles. As motor neurons are lost, muscles gradually weaken, waste away (atrophy), and eventually cease to function. This affects voluntary movement, speech, swallowing, and ultimately breathing. Most forms of ALS have no known genetic cause, but approximately 5–10% of cases are familial (inherited), and among these, mutations in the SOD1 gene account for roughly 12–23% of cases.
In SOD1-ALS, mutations in the SOD1 gene produce an abnormal form of the SOD1 protein that misfolds and accumulates within motor neurons. This toxic protein accumulation triggers a cascade of cellular damage, including oxidative stress, mitochondrial dysfunction, and neuroinflammation, ultimately leading to the death of motor neurons. Unlike the normal SOD1 protein – which serves a protective antioxidant function – the mutant form gains a toxic function that drives neurodegeneration.
Qalsody works by specifically targeting SOD1 mRNA and promoting its degradation through a process involving an enzyme called RNase H1. When tofersen binds to the SOD1 mRNA, it forms a DNA-RNA hybrid that is recognised by RNase H1, which cleaves and degrades the mRNA. This reduces the total amount of SOD1 protein produced by the cell, including the toxic misfolded forms. Clinical studies have demonstrated that tofersen significantly reduces SOD1 protein levels in cerebrospinal fluid (CSF) and lowers plasma neurofilament light chain (NfL), a well-established biomarker of ongoing neuronal injury.
By reducing the burden of toxic SOD1 protein, Qalsody aims to slow or halt the destruction of motor neurons, thereby preserving muscle strength and function. It is important to note that Qalsody does not cure ALS or reverse existing damage, but it addresses the underlying molecular cause of disease in patients with confirmed SOD1 mutations. A genetic test confirming a pathogenic SOD1 mutation is required before treatment can be initiated.
What Should You Know Before Receiving Qalsody?
Contraindications
Qalsody must not be administered to patients with a known hypersensitivity (allergy) to tofersen or any of the excipients contained in the formulation. The excipients include disodium phosphate, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, sodium chloride, sodium dihydrogen phosphate dihydrate, and water for injections. If you have experienced a previous allergic reaction to any of these substances, inform your healthcare provider before treatment begins.
Additionally, Qalsody is only indicated for patients with a genetically confirmed SOD1 mutation. It will not be effective in ALS patients without this specific genetic mutation, and should not be used in those cases. Genetic testing must be completed and the results reviewed by a specialist before treatment is initiated.
Warnings and Precautions
There is an inherent risk of side effects associated with intrathecal administration via lumbar puncture. These procedure-related effects can include headache (post-lumbar puncture headache), back pain, and, less commonly, infection at the injection site. Your healthcare provider will use sterile technique and take appropriate precautions to minimise these risks.
A small number of patients treated with Qalsody have developed myelitis (inflammation of the spinal cord) or radiculitis (irritation or damage to the nerve roots). These conditions can cause symptoms including weakness, numbness, abnormal sensations (such as tingling or burning), and pain. If you notice any new neurological symptoms during treatment, it is essential to report them to your healthcare team immediately, as early recognition and management are critical.
Papilloedema (swelling of the optic nerve in the eye) and raised intracranial pressure have also been reported in patients receiving Qalsody. Symptoms may include blurred vision, double vision, reduced vision, and headache. Regular ophthalmological monitoring may be recommended during treatment. Additionally, aseptic (non-infectious) meningitis has been observed, presenting with headache, fever, neck stiffness, nausea, and vomiting. These symptoms require prompt medical evaluation.
Before starting treatment with Qalsody, your healthcare provider may request baseline blood and urine tests. Blood tests are performed to assess blood clotting function (coagulation), while urine tests evaluate kidney function. This is because other medicines in the antisense oligonucleotide class have been associated with effects on renal function and platelet counts. These tests may not be required before every dose but will be conducted periodically during treatment as determined by your physician.
Use in Children and Adolescents
Qalsody has not been studied in patients under 18 years of age. Its safety and efficacy in children and adolescents have not been established, and it should not be administered to this age group. SOD1-ALS typically presents in adulthood, though rare juvenile-onset cases have been described in the medical literature. If a paediatric patient is suspected of having SOD1-ALS, treatment decisions should be made on a case-by-case basis by a specialist in neurodegenerative diseases, weighing potential benefits against unknown risks.
Pregnancy and Breastfeeding
Qalsody is not recommended during pregnancy. The effects of tofersen on the developing foetus have not been adequately studied in humans, and based on precautionary principles, women of childbearing potential should use effective contraception during treatment. If you discover you are pregnant while receiving Qalsody, inform your healthcare provider immediately so that the risks and benefits of continuing treatment can be carefully evaluated.
It is not known whether tofersen passes into breast milk. A decision must be made whether to discontinue breastfeeding or to discontinue Qalsody treatment, taking into account the benefit of treatment for the mother and the benefit of breastfeeding for the infant. Your doctor will help you weigh these considerations and arrive at the best decision for your individual circumstances.
Driving and Using Machines
Qalsody may affect your ability to drive or operate machinery. If you experience changes in your vision during treatment – such as blurred or double vision – you should not drive or operate machinery until your vision returns to normal. This is particularly relevant given the known risk of papilloedema and raised intracranial pressure associated with Qalsody. Additionally, the underlying progression of ALS may independently affect your ability to drive, and this should be discussed with your healthcare provider.
Interactions with Other Medicines
Tofersen is not metabolised by cytochrome P450 (CYP) enzymes and is not known to be a substrate, inhibitor, or inducer of major drug-metabolising enzymes or drug transporters. Therefore, clinically significant drug-drug interactions are not expected. However, you should always inform your healthcare provider of all medicines you are currently taking, have recently taken, or plan to take, including over-the-counter medicines, herbal supplements, and vitamins.
While no formal drug interaction studies have been conducted with tofersen, patients receiving anticoagulant therapy (blood thinners) or antiplatelet agents should be monitored carefully, as these medications may increase the risk of bleeding complications associated with the lumbar puncture procedure. Your healthcare team will consider this when planning your treatment schedule.
What Is the Correct Dosage of Qalsody?
Qalsody is administered exclusively by intrathecal injection – meaning it is delivered directly into the cerebrospinal fluid (CSF) surrounding the spinal cord via a lumbar puncture procedure. This route of administration ensures that the drug reaches its target in the central nervous system at therapeutic concentrations. The procedure involves inserting a needle into the lower back (lumbar region) into the space around the spinal cord, and it must be performed by a healthcare professional with documented experience in performing lumbar punctures.
Loading Phase
Initial Loading Doses
The loading phase consists of three doses of 100 mg tofersen, administered at 14-day intervals:
- Dose 1: Day 1 (treatment initiation)
- Dose 2: Day 15 (14 days after first dose)
- Dose 3: Day 29 (14 days after second dose)
This accelerated schedule allows rapid accumulation of tofersen in the central nervous system to achieve therapeutic levels more quickly.
Maintenance Phase
Ongoing Maintenance Doses
Following completion of the loading phase, Qalsody is administered at a dose of 100 mg every 28 days (approximately once monthly). This maintenance schedule is designed to sustain therapeutic drug concentrations in the CSF and ensure continued suppression of SOD1 protein production.
Duration of Treatment
Qalsody is intended for long-term use. Your neurologist will discuss the expected duration of treatment based on your individual response and clinical status. It is critical that you do not discontinue treatment without consulting your doctor, as interrupting therapy could lead to a rebound in SOD1 protein levels and potential acceleration of disease progression. The decision to continue or stop treatment should be made collaboratively between you and your medical team.
Missed Dose
If you miss a scheduled dose of Qalsody, contact your healthcare provider as soon as possible to arrange an alternative appointment. The missed dose should be administered at the earliest opportunity. Your treatment schedule will then continue from the date of the rescheduled dose, with subsequent maintenance doses given every 28 days from that point. Do not attempt to double up doses or alter the dosing interval without medical guidance.
Overdose
Since Qalsody is administered exclusively by healthcare professionals in a clinical setting, the risk of accidental overdose is extremely low. There is no specific antidote for tofersen overdose. In the event of an overdose, supportive care and monitoring for adverse effects – particularly neurological symptoms – would be the appropriate clinical response. If you have concerns about your dosing, discuss them with your treating physician.
| Phase | Dose | Schedule | Route |
|---|---|---|---|
| Loading – Dose 1 | 100 mg (15 mL) | Day 1 | Intrathecal (lumbar puncture) |
| Loading – Dose 2 | 100 mg (15 mL) | Day 15 | Intrathecal (lumbar puncture) |
| Loading – Dose 3 | 100 mg (15 mL) | Day 29 | Intrathecal (lumbar puncture) |
| Maintenance | 100 mg (15 mL) | Every 28 days | Intrathecal (lumbar puncture) |
How Does Qalsody Interact with Other Drugs?
One of the notable advantages of tofersen from a pharmacological perspective is its favourable drug interaction profile. Unlike many conventional small-molecule drugs, antisense oligonucleotides are not metabolised by cytochrome P450 (CYP) enzymes in the liver. Instead, tofersen is broken down by endonucleases – enzymes that cleave nucleic acid chains – through a completely different metabolic pathway. This means it does not compete with other drugs for CYP-mediated metabolism and is unlikely to alter the plasma levels of co-administered medications.
Furthermore, tofersen is not a substrate, inhibitor, or inducer of major drug transporters such as P-glycoprotein (P-gp), organic anion transporting polypeptides (OATPs), or breast cancer resistance protein (BCRP). No formal clinical drug-drug interaction studies have been conducted; however, based on the known pharmacological properties of tofersen, clinically relevant pharmacokinetic interactions are considered unlikely.
Procedural Considerations
While tofersen itself does not interact with other drugs in a traditional pharmacokinetic sense, the lumbar puncture procedure required for its administration introduces practical considerations for patients taking certain medications. Anticoagulants (such as warfarin, heparin, or direct oral anticoagulants) and antiplatelet agents (such as aspirin or clopidogrel) may increase the risk of spinal haematoma or bleeding at the puncture site. Your healthcare team will evaluate your current anticoagulation or antiplatelet therapy and may recommend temporary dose adjustments or timing modifications around the procedure.
| Medication Class | Examples | Consideration | Action |
|---|---|---|---|
| Anticoagulants | Warfarin, enoxaparin, rivaroxaban, apixaban | Increased bleeding risk during lumbar puncture | Discuss timing/adjustment with physician |
| Antiplatelet agents | Aspirin, clopidogrel, ticagrelor | Increased bleeding risk at injection site | Evaluate risk-benefit with physician |
| NSAIDs | Ibuprofen, naproxen, diclofenac | May affect platelet function | Discuss temporary discontinuation |
| Other intrathecal drugs | Baclofen, methotrexate | Potential for additive CSF effects | Coordinate administration schedules |
What Are the Side Effects of Qalsody?
Like all medicines, Qalsody can cause side effects, although not everyone will experience them. The side effects reported during clinical trials and post-marketing surveillance fall into several categories, ranging from very common procedure-related effects to rare but serious neurological complications. It is important to be aware of these potential effects so you can recognise them early and seek appropriate medical attention.
Side effects related to the lumbar puncture procedure itself may occur during or after each Qalsody administration. These can include headache (including post-lumbar puncture headache, which may worsen when sitting or standing), back pain at the injection site, and rarely, infection. Your healthcare team will provide guidance on managing post-procedure symptoms, which typically resolve within a few days.
Serious Side Effects
The most serious adverse effects observed in patients receiving Qalsody include myelitis (inflammation of the spinal cord), radiculitis (irritation and damage to spinal nerve roots), papilloedema (swelling of the optic disc caused by raised pressure), increased intracranial pressure, and aseptic meningitis (inflammation of the meninges without an infectious cause). While these events are uncommon, they can be clinically significant and require prompt evaluation and management. Myelitis and radiculitis may present with new weakness, numbness, tingling, or pain that differs from your ALS symptoms. Papilloedema may cause visual disturbances including blurring, double vision, or visual field defects.
Very Common
- Pain (back pain, pain in arms or legs)
- Fatigue and tiredness
- Musculoskeletal and joint pain (arthralgia, myalgia)
- Fever (pyrexia)
- Elevated protein levels in cerebrospinal fluid (CSF pleocytosis)
- Elevated white blood cell count in cerebrospinal fluid
Common
- Muscle stiffness (musculoskeletal stiffness)
- Nerve pain (neuropathic pain), including burning and tingling sensations
- Headache (including post-lumbar puncture headache)
Uncommon / Reported
- Myelitis (spinal cord inflammation)
- Radiculitis (nerve root inflammation and damage)
- Papilloedema (optic nerve swelling)
- Raised intracranial pressure
- Aseptic meningitis (chemical meningitis)
Procedure-Related
- Post-lumbar puncture headache (worse when upright)
- Back pain at injection site
- Injection site infection (rare)
- Cerebrospinal fluid leak
If you experience any side effects not listed above, or if existing symptoms worsen, contact your healthcare provider. Reporting suspected side effects contributes to the ongoing monitoring of the medicine's benefit-risk profile. In the European Union, side effects can be reported to the national medicines agency. In the United States, reports can be submitted to the FDA's MedWatch programme.
How Should Qalsody Be Stored?
Proper storage of Qalsody is essential to maintain the stability and efficacy of the medicine. In most cases, your healthcare facility will store and handle Qalsody, but the following information is important for awareness and patient safety.
Qalsody must be stored in a refrigerator at a temperature between 2 °C and 8 °C (36–46 °F). The vials must not be frozen at any time, as freezing may damage the molecular structure of the antisense oligonucleotide and compromise its effectiveness. The vials should be kept in the original outer carton to protect the solution from light exposure, as tofersen is light-sensitive.
For convenience in clinical settings, unopened Qalsody vials may be temporarily removed from the refrigerator and stored at room temperature (not exceeding 30 °C / 86 °F) for up to 14 days in the original packaging. Additionally, unopened vials may be removed from and returned to the refrigerator as needed, but the total time outside the refrigerator at room temperature should not exceed 6 hours per day for a maximum of 6 days.
Before administration, the solution should be visually inspected. Qalsody is a clear and colourless to slightly yellow solution for injection. If particles are visible in the solution, or if the liquid appears cloudy or discoloured, the vial should not be used and should be discarded according to local pharmaceutical waste disposal guidelines. As with all medicines, Qalsody should be kept out of the sight and reach of children, and should not be used after the expiry date printed on the carton.
What Does Qalsody Contain?
Qalsody is supplied as a solution for injection in a single-dose glass vial. Each vial contains 15 mL of solution, providing a total dose of 100 mg of tofersen (equivalent to a concentration of 6.7 mg per millilitre). The entire contents of one vial constitute a single dose.
The inactive ingredients (excipients) in Qalsody are carefully selected to create a solution that is compatible with the cerebrospinal fluid environment and suitable for intrathecal administration. These excipients include:
- Disodium phosphate – a buffering agent that helps maintain the pH of the solution
- Sodium dihydrogen phosphate dihydrate – a co-buffer that works with disodium phosphate to ensure pH stability
- Sodium chloride – used to adjust the osmolality (salt concentration) of the solution to match that of CSF
- Potassium chloride – an electrolyte that contributes to the physiological composition of the solution
- Calcium chloride dihydrate – an electrolyte present in trace amounts to mimic the ionic composition of CSF
- Magnesium chloride hexahydrate – an electrolyte that helps maintain the solution's compatibility with the central nervous system environment
- Water for injections – the solvent base, meeting pharmacopoeial standards for sterile preparations
The formulation is designed to closely resemble the electrolyte composition of normal cerebrospinal fluid, minimising the risk of irritation when the drug is injected into the intrathecal space. Each package contains one single-dose vial. Qalsody is manufactured by Biogen Netherlands B.V. and is available by prescription only through specialist neurological centres.
Frequently Asked Questions About Qalsody
Qalsody (tofersen) is used to treat amyotrophic lateral sclerosis (ALS) in adults who have a confirmed mutation in the superoxide dismutase 1 (SOD1) gene. SOD1-ALS is a rare genetic form of motor neuron disease that accounts for approximately 2% of all ALS cases. Tofersen works by reducing the levels of toxic SOD1 protein in the central nervous system, helping to slow the progressive destruction of motor neurons that leads to muscle weakness, wasting, and loss of function.
Qalsody is administered as an intrathecal injection via lumbar puncture – a procedure where a needle is inserted into the lower back to deliver the medicine directly into the cerebrospinal fluid surrounding the spinal cord. The treatment begins with a loading phase of three doses given at 14-day intervals (days 1, 15, and 29), followed by maintenance doses every 28 days. The procedure must be performed by a healthcare professional experienced in lumbar punctures, typically a neurologist or specialist nurse.
The most serious risks include myelitis (inflammation of the spinal cord), radiculitis (nerve root inflammation), papilloedema (swelling of the optic nerve), raised intracranial pressure, and aseptic meningitis. Warning signs to watch for include new or worsening weakness, numbness, tingling, pain, blurred or double vision, severe headache, fever, and neck stiffness. If you experience any of these symptoms, seek immediate medical attention. Regular monitoring during treatment helps detect these complications early.
SOD1-ALS is a form of amyotrophic lateral sclerosis caused by mutations in the SOD1 gene, which provides instructions for making the superoxide dismutase 1 protein. It accounts for about 2% of all ALS cases and 12–23% of familial (inherited) cases. Diagnosis requires a genetic test that identifies a pathogenic mutation in the SOD1 gene. Your neurologist can arrange this test, which is typically performed on a blood sample. Not all SOD1 mutations cause ALS, so the results must be interpreted by a genetics specialist in the context of your clinical presentation.
Qalsody was approved under “exceptional circumstances” by the European Medicines Agency (EMA) and received accelerated approval from the US FDA, recognising that complete clinical data is inherently limited due to the extreme rarity of SOD1-ALS. The pivotal VALOR Phase 3 trial demonstrated significant reductions in neurofilament light chain (NfL), a biomarker of neuronal damage, and in CSF SOD1 protein levels. The open-label extension study showed sustained biomarker improvements and trends toward slowing functional decline. Regulatory agencies review new evidence annually to confirm the ongoing benefit-risk balance.
Qalsody is not recommended during pregnancy, and women of childbearing potential should use effective contraception during treatment. The effects of tofersen on the developing foetus have not been adequately studied. For breastfeeding mothers, a decision must be made in consultation with your doctor about whether to stop breastfeeding or discontinue treatment, weighing the benefits of each. If you become pregnant during treatment or are planning a pregnancy, contact your healthcare provider immediately.
References and Sources
This article is based on peer-reviewed clinical evidence, regulatory assessment reports, and established international medical guidelines. All medical claims follow the GRADE evidence framework and have been reviewed by our medical editorial team.
- European Medicines Agency (EMA). Qalsody (tofersen) – EPAR Product Information. European Medicines Agency, 2024. Available at: ema.europa.eu
- Miller TM, Cudkowicz ME, Genge A, et al. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. New England Journal of Medicine. 2022;387(12):1099–1110. doi:10.1056/NEJMoa2204705
- Benatar M, Wuu J, Andersen PM, et al. Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Mutation Carriers: the ATLAS Study. Neurotherapeutics. 2022;19(4):1248–1258.
- US Food and Drug Administration (FDA). Qalsody Prescribing Information. FDA, 2023.
- Biogen Inc. Qalsody (tofersen) Summary of Product Characteristics (SmPC). Biogen Netherlands B.V., 2024.
- Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. New England Journal of Medicine. 2017;377(2):162–172.
- Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362(6415):59–62.
- World Health Organization (WHO). ALS and Motor Neuron Diseases: Global Health Estimates. WHO, 2023.
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in neurology, clinical pharmacology, and neurodegenerative disease. Our editorial process follows evidence-based medicine principles and international clinical guidelines.