viltolarsen

Action and Spectrum

Actions and spectrum: 

Actions of viltolarsen: viltolarsen is designed to work by targeting specific genetic mutations in the dystrophin gene that lead to the absence or malfunction of the dystrophin protein. It acts as an antisense oligonucleotide, which is a short segment of synthetic DNA or RNA that binds to a specific region of messenger RNA (mRNA). By binding to the targeted mRNA sequence, viltolarsen induces exon skipping during the mRNA splicing process. 

Spectrum of viltolarsen: viltolarsen is designed to be effective in individuals with specific genetic mutations in the dystrophin gene known as amenable mutations. These mutations create a “stop codon” within the gene, leading to the premature termination of dystrophin production. viltolarsen is intended to skip over the exon containing the stop codon during mRNA splicing, allowing the production of a partially functional dystrophin protein. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

reaction at Injection site (25%) 

Pyrexia (19%) 

Arthralgia (13%) 

Vomiting (13%) 

decreased Ejection fraction (13%) 

URTI (63%) 

Cough (19%) 

Confusion (13%) 

Diarrhea (13%) 

Abdominal pain (13%) 

Urticaria (13%) 

Black Box Warning

Black Box Warning:  

there was no black box warning specifically reported for viltolarsen 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

there were no specific contraindications listed for viltolarsen  

Caution: 

• Allergic Reactions: Patients should be monitored for signs of allergic reactions or hypersensitivity, such as rash, itching, swelling, or difficulty breathing. If any allergic reactions occur, medical attention should be sought immediately. 
• Injection Site Reactions: The reactions, such as pain, redness, swelling, or bruising, may occur with viltolarsen administration. Patients should be recommended to notify their healthcare provider if they experience persistent or worsening injection site reactions. 
• Coagulation Disorders: Patients with bleeding disorders or those taking anticoagulant medications may have an increased risk of bleeding at the injection site. Appropriate precautions and monitoring should be undertaken in such cases. 
• Interactions with Other Medications: Viltolarsen may interact with other medications, including those that affect blood clotting or platelet function. Patients should inform their healthcare provider about all the medications they are taking, including over-the-counter drugs, supplements, and herbal products. 
• Potential Kidney or Liver Effects: As with any medication, viltolarsen may have potential effects on kidney or liver function. Patients with pre-existing kidney or liver conditions should be closely monitored while receiving treatment. 

Comorbidities: 

• Cardiac Dysfunction: DMD often leads to progressive cardiac muscle weakness and can result in cardiomyopathy, arrhythmias, and heart failure. Close monitoring of cardiac function is crucial in patients with DMD, and appropriate cardiac interventions and management strategies may be necessary. 
• Respiratory Complications: Respiratory muscles can be affected in DMD, leading to respiratory insufficiency and the need for respiratory support such as non-invasive ventilation or tracheostomy. Regular monitoring of respiratory function and timely interventions are important to manage respiratory complications. 
• Orthopedic Issues: Progressive muscle weakness in DMD can lead to skeletal deformities, scoliosis, contractures, and joint problems. Orthopedic interventions, such as braces, surgery, or physical therapy, may be necessary to manage these complications. 
• Nutritional and Gastrointestinal Challenges: Some individuals with DMD may have difficulty with nutrition and may require dietary modifications or nutritional support. Gastrointestinal issues such as constipation and gastroesophageal reflux disease (GERD) may also be observed and need to be managed appropriately. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

viltolarsen is an antisense oligonucleotide designed to target specific genetic mutations in the dystrophin gene associated with Duchenne muscular dystrophy (DMD). 

viltolarsen acts by binding to a specific region of the dystrophin pre-messenger RNA (mRNA), which is the genetic blueprint for the dystrophin protein. This binding enables the skipping of specific exons during mRNA splicing. By skipping certain exons, viltolarsen allows to produce a truncated but functional form of the dystrophin protein.  

Pharmacodynamics: 

• Targeted Genetic Mutations: viltolarsen is specifically designed to target certain genetic mutations in the dystrophin gene associated with Duchenne muscular dystrophy (DMD). These mutations create premature stop codons that lead to the production of non-functional or truncated dystrophin protein. 
• Exon Skipping: viltolarsen acts as an antisense oligonucleotide that binds to a specific region of the dystrophin pre-mRNA. This binding facilitates the process of exon skipping during mRNA splicing. Exon skipping allows for the exclusion of specific exons in the mRNA, resulting in the production of a shorter but functional form of the dystrophin protein. 
• Dystrophin Restoration: The primary pharmacodynamic effect of viltolarsen is the restoration of dystrophin protein expression in muscle cells. By promoting the production of a truncated yet functional dystrophin protein, viltolarsen aims to improve muscle fiber stability and function in individuals with DMD who have specific genetic mutations amenable to exon skipping therapy. 
• Muscle Fiber Stability and Function: The restoration of functional dystrophin protein is expected to help maintain the structural integrity and proper functioning of muscle fibers. This can potentially slow down disease progression, reduce muscle degeneration, and improve muscle strength and mobility in patients with DMD. 

Pharmacokinetics: 

Absorption 

viltolarsen is administered via intravenous infusion, which allows for direct and complete delivery into the bloodstream. Intravenous administration typically results in rapid and complete absorption. 

Distribution 

After absorption, viltolarsen is expected to distribute throughout the body via the systemic circulation. The specific distribution characteristics, such as tissue penetration and binding to plasma proteins, are not readily available. 

Metabolism 

The metabolism of viltolarsen is not extensively described in the available information. However, as an oligonucleotide, it may undergo degradation by cellular nucleases or other enzymatic processes. Metabolism of viltolarsen may also occur in the liver or other tissues. Detailed information regarding specific metabolites or metabolic pathways is not readily available. 

Elimination and excretion 

The excretion of viltolarsen is primarily expected to occur via renal excretion, as is the case with many small nucleic acid-based drugs. The elimination half-life and clearance rates of viltolarsen are not readily available. 

Adminstartion

Administration: 

viltolarsen is administered through intravenous infusion. It is typically administered by a healthcare professional in a clinical setting such as a hospital or infusion center. The exact dosage and administration schedule should be determined by specific needs and condition of the patient. 

During the infusion, viltolarsen is delivered directly into the bloodstream through a vein. The infusion is typically performed over a certain period of time, which may vary depending on the specific dosing regimen prescribed by the healthcare professional. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: viltolarsen 

Pronounced: (vil-toe-LAR-sen)  

Why do we use viltolarsen? 

viltolarsen is used for the treatment of Duchenne muscular dystrophy who have genetic mutations amenable to exon skipping therapy. DMD is a genetic disorder which is characterized by the absence or deficiency of the dystrophin protein, resulting in progressive muscle degeneration and weakness. 

viltolarsen is specifically indicated for patients with mutations of the DMD gene. By promoting exon skipping during the mRNA splicing process, viltolarsen helps restore the production of a truncated but functional form of the dystrophin protein. This truncated dystrophin protein can improve muscle fiber stability and function. 

The goal of viltolarsen treatment is to slow down the progression of muscle degeneration, improve muscle strength, and potentially delay the loss of ambulation in patients with DMD who have the specific genetic mutation that can be targeted by viltolarsen.