Qalsody (tofersen)
Qalsody has been provisionally approved for the treatment of adults with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene. Qalsody contains the active ingredient tofersen.
Qalsody has provisional approval in Australia for treating adults with a rare form of amyotrophic lateral sclerosis (ALS) caused by a mutation (defect) in the superoxide dismutase 1 (SOD1) gene.
ALS is a type of motor neurone disease (MND), a progressive condition that affects motor neurons. Motor neurons are nerve cells that control muscle movement. They send messages from the brain and spinal cord to the muscles, allowing people to move, speak, swallow and breathe.
In people with ALS, the motor neurons gradually stop working and die, causing muscles to become weaker over time. The way ALS progresses differs from person to person, but it usually gets worse over time and is life-limiting.
Around 2% of people with ALS develop the disease because of defects in the SOD1 gene. This form of the disease is known as SOD1-associated ALS, or SOD1-ALS.
The SOD1 gene normally makes a protein that helps protect cells by breaking down harmful molecules. When the SOD1 gene is defective, the protein can become abnormal and damage motor neurons.
The altered SOD1 gene causes a build-up of toxic SOD1 protein. This causes loss of nerve cells in the brain and spine, leading to weakness in muscles, including those used for breathing and swallowing.
Qalsody works by reducing the build-up of SOD1 protein. This helps to prevent the loss of nerve cells and may slow the loss of muscle strength.
Qalsody is given by injection into the lower back. This injection, called a lumbar puncture, is done by inserting a needle in the space around the spinal cord (intrathecal space). This will be done by a doctor experienced in doing lumbar punctures.
There is currently no cure for ALS and treatment options are limited. On average, people with ALS live for approximately 2 to 3 years after diagnosis.
The type of ALS caused by defects in the SOD1 gene is rare. This makes it hard to collect clinical evidence about new treatments. Research is still ongoing to learn how well treatments work for people with SOD1-ALS and how safe they are over the longer term.
The effectiveness and safety of Qalsody were assessed in one main clinical study and a supporting study.
The main clinical study compared the effectiveness and safety of Qalsody to a placebo (a control treatment with no active medicine) in patients with SOD1-ALS. The study included 108 patients, aged 23 to 78 years, and went for 28 weeks.
The supporting study is an extension of the main study to gather information over a longer period.
In the main study, results did not show a statistically significant effect of the medicine on the primary endpoint after 28 weeks of treatment. However, other measurements confirmed the way the medicine is expected to work and indicated that Qalsody may slow down the course of the disease.
With longer follow-up in the extension study, patients who were given Qalsody in the main study showed less decline in measures of daily function, breathing, and strength. They also appeared to have a longer time before death or need for permanent breathing support, compared with patients who started Qalsody in the extension study (approximately 6 months later). Across both groups, patients given Qalsody had better outcomes than would be expected for untreated ALS over 4.9 years of follow up.
The sponsor company is continuing to carry out research to better understand the longer-term benefits, safety and survival outcomes of Qalsody.
Key findings from the clinical studies
Main study – Qalsody compared with placebo in patients with SOD1-ALS
At 28 weeks, patients who were given Qalsody showed:
- slightly less decline in daily function and quality of life compared with placebo, based on a scale used to assess daily functioning
- trends suggesting slower decline in breathing strength (measured by slow vital capacity, a lung function test) and muscle strength (measured using handheld dynamometry)
- a 35% reduction in total SOD1 protein in the fluid around the brain and spinal cord, compared with a 2% reduction in patients given placebo
- a 55% reduction in plasma neurofilament light chain (NfL), a sign of nerve damage, compared with a 12% increase with placebo, suggesting less nerve damage.
Importantly, the reductions in SOD1 protein and NfL show that Qalsody had the expected biological effect.
Integrated results – main study and extension study
At 148 weeks, patients who had received Qalsody in the main study (and therefore started Qalsody treatment 6 months earlier than those who initially received placebo):
- continued to have lower SOD1 protein and NfL levels for 148 weeks, suggesting sustained slowing of nerve damage
- continued to report less decline in daily function, breathing and strength
- showed smaller declines in lung function and muscle strength
- appeared to have a longer time before death or need for permanent breathing support.
Some patients given Qalsody also showed improvements in lung function, muscle strength and/or daily function over about 3 years, particularly those who started treatment earlier.
Patients who initially received placebo and started Qalsody treatment approximately 6 months later showed reductions in SOD1 protein and NfL levels that were similar to those who received Qalsody earlier.
Taken together, the available evidence suggests that Qalsody provides benefits for people with SOD1-ALS.
Adverse events (problems or side effects)
- The most common adverse events in patients given Qalsody (reported in at least 1 in 10 patients) were pain, muscle pain, joint pain, fatigue, increased white blood cells and protein in the fluid around the brain and spinal cord, and fever.
- Adverse events considered to be related to the lumbar puncture were reported in 85.7% of study participants overall.
- For comprehensive information on potential side effects and risks, refer to the Consumer Medicine Information (CMI) leaflet or Product Information (PI) document.
Assessment decision
The TGA’s decision to grant provisional approval was made on all the evidence considered together. This included effects on daily function, breathing function, muscle strength, survival, reduced NfL, and evidence that the medicine worked as intended in people with SOD1-ALS. Continued approval of this indication for use depends on additional data.
More detailed information on why the TGA approved Qalsody will be published in the upcoming Australian Public Assessment Report (AusPAR).
This decision summary will not be updated to reflect any subsequent changes and may therefore not contain the most current information about the medicine. For the latest information, refer to the medicine’s CMI or PI.
The CMI leaflet offers guidance for consumers to support safe and effective use of the medicine. The CMI includes information on dose, how to use the medicine properly, potential side effects, safety precautions, storage instructions and more.
The Australian CMI for Qalsody can be accessed through the searchable TGA eBusiness Services or ARTG databases.
The PI document provides essential prescribing information for health professionals, including details on dosage recommendations, pregnancy category, contraindications, precautions and potential side effects.
The Australian PI for Qalsody can be accessed through the searchable TGA eBusiness Services or ARTG databases.
For health advice and information, including a symptom checker and service finder refer to the healthdirect website.
For advice on prescription medicines, over the counter medicines and other medicines (including complementary medicines) call Medicines Line.
For information on medicines subsidised by the Australian Government refer to the Pharmaceutical Benefits Scheme (PBS) website.
For data and reports on health and welfare topics in Australia refer to the Australian Institute of Health and Welfare website.
Qalsody is given into the fluid around the spine using a lumbar puncture. This is done by, or under the guidance of, healthcare professionals who are trained and experienced in performing this procedure.