What Is Qalsody (Tofersen)?
Tofersen is an antisense oligonucleotide indicated for treating amyotrophic lateral sclerosis (ALS) [citation]. The FDA approved Tofersen on April 21, 2023. The drug received accelerated approval due to good results related to the neurofilament light chain (NfL) treatment, with the need for further trials and checks.
For What Is Used Qalsody (Tofersen)?
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease caused by many factors, but 2% are linked to the SOD1 mutation [citation]. More than 200 variants of the SOD1 protein have been reported so far, and Tofersen is used to reduce the synthesis of this protein [citation; citation].
Given that this disease has a genetic component, treatment and diagnosis should be established promptly and require a unique treatment approach. Furthermore, studies have also revealed presymptomatic markers of the disease ALS, such as elevation in the blood NfL [citation].
Who Developed Qalsody (Tofersen)?
Qalsody (Tofersen) is manufactured by Biogen MA Inc, a global biotechnology company [citation]. Biogen MA Inc, commonly known as Biogen, is a multinational biotechnology company specializing in developing and manufacturing therapies for neurological and neurodegenerative diseases. The company focuses on researching, discovering, and delivering innovative treatments to address conditions such as multiple sclerosis (MS), spinal muscular atrophy (SMA), Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).
What Is the Mechanism of Action?
The data indicate multiple mutations or variants on the SOD1 protein, whose function and effect on the disease still need to be thoroughly investigated. It is believed that the essential role of SOD1 in ALS is the toxic gain of function [citation].
Tofersen was therefore developed to influence the development of the disease by reducing the synthesis of SOD1 protein via ribonuclease H-dependent degradation of SOD1 mRNA [citation].
What Is a Toxic Gain of Function?
Toxic gain of function refers to a phenomenon where a mutation or alteration in a gene results in the acquisition of new or enhanced protein functions being encoded by the given gene that is detrimental to cellular or organismal health. In contrast to the loss of function mutations, which typically lead to a decrease or loss of normal protein function, the toxic gain of function mutations results in the production of a protein with novel properties that are harmful to the cell or organism.
In the context of genetic diseases, the toxic gain of function mutations can occur when a mutation causes a protein to have abnormal or excessive activity, disrupting cellular processes and contributing to disease development. These mutations may produce a toxic protein that is toxic to cells, interferes with regular protein-protein interactions, disrupts signaling pathways, or aggregates and forms harmful deposits.
Besides amyotrophic lateral sclerosis (ALS), toxic gain of function mutations have been implicated in other neurodegenerative genetic disorders such as Alzheimer's, Parkinson's, and Huntington's disease. In these conditions, specific gene mutations produce proteins that have toxic effects on neurons, leading to their dysfunction and eventual cell death.
What Are the Key Advantages of Qalsody (Tofersen)?
The main advantages of this drug are
Reduction in plasma neurofilament light chain (NfL; a blood-based biomarker of axonal injury and neurodegeneration)
Decreased toxic mutated SOD1 enzyme synthesis [citation].
Additionally, in clinical trials related to ALS, Tofersen showed the most effective results among 53 drugs [citation].
What Are the Key Warnings and Precautions?
Warnings refer to the appearance of the following signs:
Aseptic meningitis,
Papilledema and elevated intracranial pressure,
Myelitis and Radiculitis [citation].
Because such phenomena can be severe, strict monitoring and evaluation before prescribing the drug are recommended.
What Are the Key Adverse Reactions?
Characteristic side effects that occur in a percentage of 10 or more are the following:
Pain,
Arthralgia,
Myalgia,
Fatigue,
and Increase of cerebrospinal white blood cells [citation].