Clinical data | |
---|---|
Trade names | Qalsody |
License data | |
Routes of administration | Intrathecal |
ATC code |
|
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
DrugBank | |
UNII | |
KEGG | |
Chemical and physical data | |
Formula | C230H317N72O123P19S15 |
Molar mass | 7127.85 g·mol−1 |
Tofersen, sold under the brand name Qalsody, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS). [2] Tofersen is an antisense oligonucleotide that targets the production of superoxide dismutase 1, an enzyme whose mutant form is commonly associated with ALS. It is administered as an intrathecal injection into the spinal cord. [2]
The most common side effects include fatigue, arthralgia (joint pain), increased cerebrospinal (brain and spinal cord) fluid white blood cells, and myalgia (muscle pain). [2]
Tofersen was approved for medical use in the United States in April 2023. [2] [3]
Tofersen is indicated to treat people with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS). [2]
Tofersen was developed by Ionis Pharmaceuticals and was licensed to, and co-developed by, Biogen. [4] [5]
The effectiveness of tofersen was evaluated in a 28-week, randomized, double-blind, placebo-controlled clinical study in 147 participants with weakness attributable to amyotrophic lateral sclerosis and a superoxide dismutase 1 (SOD-1) mutation confirmed by a central laboratory. [2] The study randomly assigned 108 participants in a 2:1 ratio to receive treatment with either tofersen 100 mg (n = 72) or placebo (n = 36) for 24 weeks (three loading doses followed by five maintenance doses). [2] The participants were approximately 43% female; 57% male; 64% White; and 8% Asian. [2] The average age was 49.8 years (range from 23 to 78 years). [2]
The US Food and Drug Administration (FDA) granted the application for tofersen priority review, orphan drug, and fast track designations. [2]
Only around 1-2% of ALS cases diagnosed in the United States each year carry the specific SOD1 mutation targeted by the drug. [6] Fewer than 500 patients a year are expected to be eligible for the drug, which is expected to cost over $100,000 for a year's treatment. [2] [7] [8] [9]
Superoxide dismutase (SOD, EC 1.15.1.1) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide (O−
2) radical into ordinary molecular oxygen (O2) and hydrogen peroxide (H
2O
2). Superoxide is produced as a by-product of oxygen metabolism and, if not regulated, causes many types of cell damage. Hydrogen peroxide is also damaging and is degraded by other enzymes such as catalase. Thus, SOD is an important antioxidant defense in nearly all living cells exposed to oxygen. One exception is Lactobacillus plantarum and related lactobacilli, which use a different mechanism to prevent damage from reactive O−
2.
Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide.
Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-mRNA, direct steric blockage, and exon content modulation through splicing site binding on pre-mRNA. Several ASOs have been approved in the United States, the European Union, and elsewhere.
Riluzole is a medication used to treat amyotrophic lateral sclerosis and other motor neuron diseases. Riluzole delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Riluzole is available in tablet and liquid form.
Following is a list of topics related to life extension:
Progressive bulbar palsy (PBP) is a medical condition. It belongs to a group of disorders known as motor neuron diseases. PBP is a disease that attacks the nerves supplying the bulbar muscles. These disorders are characterized by the degeneration of motor neurons in the cerebral cortex, spinal cord, brain stem, and pyramidal tracts. This specifically involves the glossopharyngeal nerve (IX), vagus nerve (X), and hypoglossal nerve (XII).
Mecasermin rinfabate, also known as rhIGF-1/rhIGFBP-3, is a drug consisting of recombinant human insulin-like growth factor 1 (IGF-1) and recombinant human insulin-like growth factor binding protein-3 (IGFBP-3) which is used for the treatment of amyotrophic lateral sclerosis.
Canine degenerative myelopathy, also known as chronic degenerative radiculomyelopathy, is an incurable, progressive disease of the canine spinal cord that is similar in many ways to amyotrophic lateral sclerosis (ALS). Onset is typically after the age of 7 years and it is seen most frequently in the German shepherd dog, Pembroke Welsh corgi, and boxer dog, though the disorder is strongly associated with a gene mutation in SOD1 that has been found in 43 breeds as of 2008, including the wire fox terrier, Chesapeake Bay retriever, Rhodesian ridgeback, and Cardigan Welsh corgi. Progressive weakness and incoordination of the rear limbs are often the first signs seen in affected dogs, with progression over time to complete paralysis. Myelin is an insulating sheath around neurons in the spinal cord. One proposed cause of degenerative myelopathy is that the immune system attacks this sheath, breaking it down. This results in a loss of communication between nerves in lower body of the animal and the brain.
Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or hSod1 is an enzyme that in humans is encoded by the SOD1 gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis, familial amyotrophic lateral sclerosis and Parkinson's disease.
Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common form of the motor neuron diseases. Early symptoms of ALS include stiff muscles, muscle twitches, and gradual increasing weakness and muscle wasting. Limb-onset ALS begins with weakness in the arms or legs, while bulbar-onset ALS begins with difficulty speaking or swallowing. Around half of people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Motor neuron loss continues until the ability to eat, speak, move, and finally the ability to breathe is lost.
Edaravone, sold under the brand name Radicava among others, is a medication used to treat stroke and amyotrophic lateral sclerosis (ALS). It is given by intravenous infusion and by mouth.
Abacavir/dolutegravir/lamivudine, sold under the brand name Triumeq among others, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It is a combination of three medications with different and complementary mechanisms of action: abacavir, dolutegravir and lamivudine.
Ionis Pharmaceuticals, Inc. is a biotechnology company based in Carlsbad, California, that specializes in discovering and developing RNA-targeted therapeutics. The company has 3 commercially approved medicines: Spinraza (Nusinersen), Tegsedi (Inotersen), and Waylivra (Volanesorsen) and has 4 drugs in pivotal studies: tominersen for Huntington’s disease, tofersen for SOD1-ALS, AKCEA-APO(a)-LRx for cardiovascular disease, and AKCEA-TTR-LRx for all forms of TTR amyloidosis.
Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder.
There are more than 25 genes known to be associated with amyotrophic lateral sclerosis (ALS) as of June 2018, which collectively account for about 70% of cases of familial ALS (fALS) and 10% of cases of sporadic ALS (sALS). About 5–10% of cases of ALS are directly inherited. Overall, first-degree relatives of an individual with ALS have a 1% risk of developing ALS. ALS has an oligogenic mode of inheritance, meaning that mutations in two or more genes are required to cause disease.
Research on amyotrophic lateral sclerosis (ALS) has focused on animal models of the disease, its mechanisms, ways to diagnose and track it, and treatments.
Merit Cudkowicz is an American neurologist and neuroscientist who studies amyotrophic lateral sclerosis (ALS). Cudkowicz is Julieanne Dorn Professor of Neurology at Harvard Medical School, director of the ALS clinic and the Neurological Clinical Research Institute at Massachusetts General Hospital (MGH) and chair of the Department of Neurology at MGH. Cudkowicz has led several large scale collaborations and clinical trials to test novel treatments for ALS and as of 2020 researches ways to detect early biomarkers of ALS to improve diagnosis.
Casimersen, sold under the brand name Amondys 45, is an antisense oligonucleotide medication used for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the dystrophin gene that is amenable to exon 45 skipping. It is an antisense oligonucleotide of phosphorodiamidate morpholino oligomer (PMO). Duchenne muscular dystrophy is a rare disease that primarily affects boys. It is caused by low levels of a muscle protein called dystrophin. The lack of dystrophin causes progressive muscle weakness and premature death.
Sodium phenylbutyrate/ursodoxicoltaurine, also known as sodium phenylbutyrate/taurursodiol and sold under the brand name Albrioza among others, is a fixed-dose combination medication used for the treatment of amyotrophic lateral sclerosis (ALS). It contains sodium phenylbutyrate and ursodoxicoltaurine (taurursodiol).
Nikolay V. Dokholyan is an American biophysicist, academic and researcher. He is a G. Thomas Passananti Professor and Vice Chair for Research at Penn State College of Medicine.