casimersen

Action and Spectrum

Actions and spectrum: 

casimersen (tradename: Amondys 45) is a medication used for the treat patients with Duchenne muscular dystrophy (DMD) where there is a mutation of the DMD gene which is amenable to exon 45 skipping. DMD is a genetic disorder which causes progressive muscle degeneration and weakness, which can lead to difficulty in walking, breathing and heart problems.

casimersen is an antisense oligonucleotide that binds to exon 45 of the dystrophin gene and restores the reading frame of the mRNA, leading to the production of a shortened, yet partially functional dystrophin protein. This results in improved muscle function and a reduction in the severity of symptoms associated with DMD. casimersen is administered via intravenous infusion. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Oropharyngeal pain (21%) 

Arthralgia (21%) 

Headache (32%) 

Cough (33%) 

Pyrexia (33%) 

Upper respiratory tract infections (65%)  

>10% 

Reported 5% more when compared with placebo 

• Ear pain 
• Ear infection 
• Dizziness 
• Nausea 
• Post-traumatic pain 
• Lightheadedness 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

There are no known contraindications for casimersen. However, it is important to inform the healthcare provider of any allergies, medications, or medical conditions before initiating the therapy with casimersen.  

Caution: 

• Risk of bleeding: casimersen can increase the risk of bleeding in patients who are also taking anticoagulants or have a bleeding disorder. 
• Kidney problems: casimersen may cause kidney problems, so it should be used under caution in patients with a history of kidney disease or those who are taking other medications that can affect kidney function. 
• Hepatic impairment: casimersen has not been studied in patients with severe hepatic impairment, so caution is advised when using this medication in this population. 
• Allergic reactions: casimersen can cause allergic reactions, including anaphylaxis. Patients should be monitored for signs of allergic reactions and should discontinue the medication immediately if any occur. 
• Use with other medications: casimersen may interact with other medications, so patients should inform their healthcare provider about all medications they are taking, including over-the-counter medications, vitamins, and supplements.

Comorbidities: 

• Cardiac problems: DMD can cause heart problems such as cardiomyopathy, which may require additional treatment. 
• Respiratory problems: DMD can also affect the muscles used for breathing, which may lead to respiratory failure. This can be managed with respiratory support devices. 
• Osteoporosis: Reduced mobility and muscle weakness associated with DMD can lead to bone loss and increased risk of fractures. 
• Gastrointestinal problems: Some people with DMD may experience gastrointestinal issues such as constipation or difficulty swallowing. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category N 

Lactation: safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

casimersen is an antisense oligonucleotide drug that is designed to bind to a specific RNA sequence in the dystrophin gene, a gene that is mutated in patients with Duchenne muscular dystrophy (DMD). It is a synthetic molecule that acts by hybridizing to the targeted RNA sequence, leading to the degradation of the RNA by the RNAse H enzyme. This, in turn, promotes the expression of a truncated, yet functional, form of dystrophin protein. 

casimersen is an exon-skipping drug, which means it targets a specific exon of the dystrophin gene (exon 45), allowing the exons before and after it to join together, resulting in a shorter but functional dystrophin protein. This therapy is only effective for patients with specific DMD mutations that affect exon 45.  

Pharmacodynamics: 

casimersen is a phosphorodiamidate morpholino oligomer (PMO) which bind to exon 45 of the dystrophin gene, allowing for skipping of exon 45 during pre-mRNA splicing in patients with Duchenne muscular dystrophy (DMD). This results in the production of a truncated but functional dystrophin protein that can improve muscle function in DMD patients with genetic mutations amenable to exon 45 skipping. 

Dystrophin is a protein involved in muscle fiber structure and function, and mutations in the dystrophin gene are responsible for DMD, a progressive and debilitating muscle-wasting disease. By promoting the production of a partially functional dystrophin protein, casimersen may improve muscle strength and function in DMD patients. 

The exact pharmacodynamic effects of casimersen may vary depending on the specific mutation being targeted and the patient’s individual genetic profile.  

Pharmacokinetics: 

Absorption 

casimersen is administered via subcutaneous injection, and its absorption is expected to be complete. After injection, the drug is gradually absorbed into the systemic circulation, where it can exert its therapeutic effects on the target tissue.  

Distribution 

casimersen is a synthetic antisense oligonucleotide (ASO) and its distribution in the body is not well characterized. As an ASO, casimersen is designed to bind specifically to messenger RNA (mRNA) and inhibit the production of certain proteins, such as dystrophin  

Metabolism 

casimersen is an antisense oligonucleotide drug that is designed to hybridize with a specific RNA molecule involved in the splicing of dystrophin pre-mRNA in patients with Duchenne muscular dystrophy (DMD). As an antisense oligonucleotide, casimersen does not undergo metabolism in the conventional sense. Instead, it binds to the target RNA molecule and modulates its activity, leading to the production of functional dystrophin protein in DMD patients.  

Elimination and excretion 

casimersen is an oligonucleotide and is primarily metabolized into smaller nucleotides, which are further broken down into nucleosides and nucleobases. The elimination of these metabolites occurs primarily via urinary excretion. 

Adminstartion

Administration: 

casimersen is administered through subcutaneous injection. It is injected under the skin once a week, with the initial dose of 30 mg/kg followed by weekly doses of 30 mg/kg. The medication should be stored in the refrigerator at a temperature between 2°C to 8°C and should not be frozen.

Before administration, the medication should be brought to room temperature, and any unused portions of the medication should be discarded appropriately. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: casimersen 

Pronounced: [ KAS-i-MER-sen ]  

Why do we use casimersen? 

casimersen is a medication used to treat Duchenne muscular dystrophy (DMD) in patients who have genetic mutations which are amenable to exon 45 skipping. DMD is a genetic disorder that affects primarily boys and is characterized by progressive muscle degeneration and weakness.

casimersen helps to skip exon 45 during the production of the dystrophin protein, which can result in a partially functional protein that helps to stabilize muscle fibers and slow the progression of the disease.