TGA grants provisional approval for registration of QALSODY™ (tofersen) for adults living with a rare genetic form of ALS¹

• The TGA has granted provisional approval for registration of QALSODY™ (tofersen), the first targeted disease-modifying treatment for people in Australia with SOD1-ALS.¹
• ALS is the most common form of motor neurone disease (MND)² and SOD1-ALS is a subtype caused by mutations in the SOD1 gene³ estimated to affect around 70 Australians⁴
• ALS results in muscle weakness and atrophy, causing people to lose independence as their ability to move, speak, eat, and eventually breathe steadily declines.^5,6

Biogen Australia welcomes the decision by the Therapeutic Goods Administration (TGA) to grant provisional approval for registration of QALSODY™ (tofersen) for the treatment of adults with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS).¹

The decision to approve this indication has been made on the totality of evidence including impacts on clinical function, respiratory function, muscle strength, survival, target engagement and reductions in NfL (a marker of axonal injury and neurodegeneration) in people with SOD1-ALS treated with QALSODY.¹

ALS is a progressive neurological condition that affects the nerve cells controlling voluntary muscle movement that results in muscle weakness and atrophy, causing people to lose independence as their ability to move, speak, eat, and eventually breathe steadily declines.⁶

Advances in genetics have shown that a proportion of ALS is caused by identifiable gene mutations (genetic subtypes), even in people with no known family history.⁷ One such genetic subtype of ALS is caused by mutations in the SOD1 gene (SOD1 ALS). In SOD1 ALS, mutations in the SOD1 gene produce unstable SOD1 protein leading to its accumulation within motor neurons, resulting in axonal damage and progressive loss of motor neurons.³

Despite increasing awareness of ALS, diagnosis is often delayed, reflecting the variability of early symptoms.⁸ Median life expectancy for ALS is three to five years from symptom onset, highlighting the seriousness and urgency of the disease.^2,8

Professor Matthew Kiernan AM, Chief Executive Officer and Institute Director at Neuroscience Research Australia and a leading Australian neurologist and clinical researcher in motor neurone disease, commented, “This represents a genuinely important advance for people with SOD1-ALS and signals what may be possible for other forms of motor neurone disease in the future.

“In day to day life, focussed therapy that addresses the underlying mechanism of motor neurone disease, can mean preserving independence for longer, maintaining mobility, strength and breathing capacity, and delaying the need for respiratory support. These effects can be more evident when treatment is started early and delivered within specialist multidisciplinary MND care services.

“Importantly, the availability of a targeted treatment reinforces the need for clinicians to act with urgency; any suspicion of ALS/MND should prompt immediate referral to a neurologist or specialist centre with experience in managing the condition, to enable timely diagnosis, genetic testing where appropriate, and access to specialist treatment.”

QALSODY is a targeted therapy for people whose ALS is caused by a SOD1 mutation.^9,10The medicine is designed to reduce the amount of harmful SOD1 protein that accumulates in nerve cells, to slow the disease.^7,10

QALSODY is administered as a monthly intrathecal injection meaning it is delivered directly into the fluid surrounding the spinal cord via a lumbar puncture. This allows the medicine to reach the central nervous system, where motor neurons affected in ALS reside. Treatment consists of a loading phase (three doses given every 14 days), followed by a maintenance phase (one dose every 28 days thereafter).¹¹

Clare Sullivan, Chief Executive Officer of MND Australia, said the registration highlights the importance of understanding the genetic causes of ALS/MND.

“This announcement reinforces why genetic testing is so important for people living with ALS and other forms of MND, as well as their families,” Clare Sullivan said.

“Identifying whether a person has a SOD1 mutation can help inform care, support participation in research, and enable informed conversations with specialist healthcare teams. We encourage people living with ALS or MND to speak with their neurologist about whether genetic testing is appropriate for them.”

Alice Tien, Managing Director of Biogen Australia and New Zealand, said Biogen remains committed to the ALS community.

“People living with ALS, and those who support them, have waited a long time to see meaningful progress against this devastating disease,” Alice Tien said.

“The registration of QALSODY reflects years of scientific effort and Biogen’s enduring commitment to the ALS community. We remain focused on listening, learning, and working alongside clinicians, researchers, advocacy organisations and people with lived experience.”

As with any medicine, QALSODY can cause side effects. Common side effects reported in QALSODY-treated participants were pain (back pain, pain in arms or legs), feeling tired, muscle and joint pain, fever, muscle stiffness or nerve pain and an increase in protein and/or white blood cell count occurring in the fluid that surrounds the brain and spinal cord.¹¹

People living with SOD1-ALS or their families seeking further information are encouraged to consult their treating healthcare professional.

ENDS

The QALSODY Consumer Medicine Information can be accessed here.

TGA indication¹⁰

QALSODY has provisional approval in Australia for the treatment of adults with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene. The decision to approve this indication has been made on the totality of evidence including impacts on clinical function, respiratory function, muscle strength, survival, target engagement and reductions in NfL (a marker of axonal injury and neurodegeneration) in SOD1-ALS patients treated with QALSODY. Continued approval of this indication depends on additional data.

About QALSODY (tofersen)^10,11

Contraindications:

• Hypersensitivity to QALSODY or any of the ingredients

Interactions:

• The co-administration of other intrathecal medicinal products with QALSODY has not been evaluated and the safety of these combinations is not known

Precautions:

• You may have a urine test (to check your kidneys) and a blood test (to check that your blood clots properly) before you start treatment. This is because other medicines in the same group as QALSODY can affect the kidneys and the cells in the blood which help clotting. These tests may not be needed every time you are given QALSODY.
• If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine. QALSODY is not recommended to be used during pregnancy and in women of childbearing potential not using contraception.

Safety:

• Common side effects may include: pain (back pain, pain in arms or legs), increase in protein and/or white blood cell count occurring in the fluid that surrounds the brain and spinal cord, feeling tired, muscle and joint pain, fever, muscle stiffness or nerve pain.
• Serious side effects may include: inflammation of the spinal cord (myelitis), irritation or inflammation of nerve roots (radiculitis), swelling of the optic nerve in the eye (papilloedema), increased pressure around the brain (increased intracranial pressure) or inflammation of the lining around the brain and spinal cord (aseptic meningitis).

Regulatory Pathway: Provisional Registration

A TGA provisional registration allows a prescription medicine for a serious or life-threatening condition to be approved for use in Australia where the potential benefit of earlier availability outweighs the risk inherent in the fact that additional data are still required. ¹²

In practice, it means:

• The TGA believes the medicine could provide important benefit, especially for a serious or life-threatening condition
• The potential benefits outweigh the risks of approving it based on earlier clinical data
• The registration is time limited (initially up to two years, with possible extensions to a maximum of six years)
• The company must continue clinical studies and provide confirmatory data on safety and effectiveness
• The company then applies to convert to a full registration.

Amyotrophic lateral sclerosis and SOD1-ALS

Amyotrophic lateral sclerosis (ALS) is a rare and progressive neurodegenerative disease that has gained global public recognition through the Ice Bucket Challenge and, in Australia, the Big Freeze.^4,5,13,14

ALS typically presents between the ages of 40 and 70 years.¹⁵ In most cases, symptoms begin in the limbs, while around one quarter of people first experience difficulties with speech or swallowing (bulbar onset), and a smaller proportion present initially with respiratory symptoms.^16,17

Mutations in the SOD1 gene causes faulty SOD1 proteins to build up inside nerve cells that control muscle movement, which damages nerves and leads to the loss of muscle function.³ SOD1‑ALS can present at a younger age and may progress more rapidly than ALS overall.³ Not all SOD1 mutations are inherited - a proportion of people with SOD1- ALS have no known family history of the disease.⁷ Genetic testing is therefore relevant for people diagnosed with ALS and not only those with a strong family history and is available through reimbursable testing pathways in appropriate clinical settings.¹⁸

About Biogen

Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, two globally co-developed treatments to address a defining pathology of Alzheimer’s disease, the first treatment to target a genetic form of ALS, the first oral treatment approved for postpartum depression, and the first approved treatment for Friedreich’s ataxia. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialised immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.

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