Amondys 45

About Casimersen

• On February 25, 2021, the FDA approved Amondys 45, also known as casimersen.
• Amondys 45 contains casimersen, an antisense oligonucleotide derived from Sarepta’s phosphorodiamidate morpholino oligomer (PMO) platform.
• Amondys 45 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients with confirmed mutations of the DMD gene amenable to exon 45 skipping. This approval is based on observed increases in dystrophin production within skeletal muscle, which is a predictive marker of clinical benefit for DMD patients.
• Amondys 45 acts as an antisense oligonucleotide targeting specific mutations in the DMD gene, facilitating exon 45 skipping. This process restores the gene’s reading frame, leading to the synthesis of a truncated yet functional dystrophin protein. Dystrophin is crucial for muscle function, and its deficiency characterizes DMD. By promoting the production of a partially functional dystrophin protein, Amondys 45 aims to enhance muscle function and decelerate disease progression in DMD patients.
• Clinical trials of Amondys 45 demonstrated a statistically significant increase in dystrophin production within skeletal muscle, indicating potential clinical benefit for DMD patients. The drug exhibited promising results in augmenting dystrophin levels, which are essential for muscle health and function in individuals with DMD. 
• Patients treated with Amondys 45 experienced notable improvements in dystrophin levels, suggesting potential clinical benefits for managing Duchenne muscular dystrophy.

Strength: 

• Each single-dose vial contains 100 mg/2 mL of Casimersen.

Recommended Dosage:

Consider antiemetics before and during Amondys 45 treatment. Inspect drug products visually before administration. Reconstitute by shaking vial(s) with 40 mL of 5% Dextrose Injection, USP, then withdraw 80 mL from a refrigerated 250 mL infusion bag of 0.9% Sodium Chloride Injection, USP. Discard 80 mL and transfer the reconstituted solution to achieve a concentration of 0.1-0.16 mg/mL. 

For immediate use, infuse within 60 minutes of reconstitution; refrigerate for delayed use and administer within 6 hours. Administer Amondys 45 as a 30-minute IV infusion via a central venous access device, and flush the catheter post-infusion. Strictly adhere to storage timelines and visually inspect products to prevent adverse events.

• The prescribed dosage of Amondys 45 is 30 milligrams per kilogram, administered once weekly via intravenous infusion lasting 35 to 60 minutes, using an in-line 0.2-micron filter. 
• In the event of a missed dose, it should be administered at the earliest opportunity following the scheduled dose.

Important:

Prior to beginning Amondys 45 treatment, discuss your current medications, medical conditions, pregnancy status, or breastfeeding intentions with your healthcare provider to assess potential interactions and customize a safe treatment plan. Report any side effects promptly to your healthcare professional. Seek personalized guidance from your doctor for any concerns or questions about Amondys 45 or your treatment regimen.

Warnings & Precautions

• Amondys 45 should not be administered if you have a known allergy to Casimersen or any components of the medication. Serious allergic reactions, such as anaphylaxis and angioedema, have been reported with Casimersen use, manifesting as difficulty breathing, chest tightness, and swelling of the mouth, face, lips, or tongue. 
• If you experience signs of hypersensitivity, it’s important to seek immediate medical attention. Your doctor will manage any allergic reactions accordingly, which may involve adjusting or stopping the Amondys 45 infusion. Continuous monitoring will be conducted until the allergic reaction resolves.
• While the clinical studies didn’t show kidney toxicity, it’s crucial to monitor kidney function closely. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be assessed before treatment. 
• Consider measuring glomerular filtration rate. Monitor urine dipstick monthly and serum cystatin C and urine protein-to-creatinine ratio every three months during treatment. Use urine free of excreted Amondys 45 for protein monitoring. If serum cystatin C or proteinuria increases persistently, refer to a pediatric nephrologist for evaluation. 
• Avoid urine protein tests using the pyrogallol red reagent to prevent false positives.

Common Amondys 45 Side Effects:

• Upper respiratory tract infection (sore throat, runny or stuffy nose, pain with swallowing)
• Cough
• Pyrexia (fever)
• Headache
• Arthralgia (joint pain)
• Oropharyngeal pain

Use in Specific Population

• Data regarding the use of Amondys 45 during pregnancy and its impact on milk production or its presence in breast milk are currently unavailable, both in human and animal studies. 
• The decision to use Amondys 45 in breastfeeding mothers should consider the potential benefits of breastfeeding alongside the clinical necessity for treatment and any possible risks to the infant from either the medication or the mother’s underlying condition. 
• It is indicated for treating Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 45 skipping, including pediatric patients. Since DMD primarily affects children and young adults, there is no experience in geriatric DMD patients. 
• No specific dosage adjustments are recommended for DMD patients with renal impairment based on the estimated glomerular filtration rate, but close monitoring is advised for those with known renal function impairment during the treatment.

Storage and Handling

• Store Amondys 45 at 2°C to 8°C (36°F to 46°F)
• Keep the medicine protected from moisture.
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.