Amondys 45

Amondys 45 Uses, Dosage, Side Effects, Food Interaction and all others data.

Duchenne muscular dystrophy (DMD) is an X-linked recessive allelic disorder characterized by a lack of functional dystrophin protein, which leads to progressive impairment of ambulatory, pulmonary, and cardiac function and is invariably fatal. A related, albeit a less severe, form of muscular dystrophy known as Becker muscular dystrophy (BMD) is characterized by shortened and partially functional dystrophin protein production. Although corticosteroids effectively slow disease progression in both DMD and BMD patients, they do not address the underlying molecular pathogenesis.

The application of antisense oligonucleotides in DMD patients with specific mutations allows for exon skipping to produce truncated BMD-like dystrophin proteins, which restore partial muscle function and slow disease progression. Amondys 45 is a phosphorodiamidate morpholino oligonucleotide (PMO); PMOs are oligonucleotides in which the five-membered ribofuranosyl ring is replaced with a six-membered morpholino ring, and the phosphodiester links between nucleotides are replaced with a phosphorodiamidate linkage. In this manner, PMOs are much less susceptible to endo- and exonucleases and exhibit drastically reduced metabolic degradation compared to traditional synthetic oligonucleotides. Amondys 45 is the most recent in a line of approved PMOs for treating DMD, including eteplirsen and viltolarsen. However, the specific mutations, and hence the precise exon skipping, targeted by each is different.

Amondys 45 was granted accelerated FDA approval on February 25, 2021, based on data showing an increase in dystrophin levels in skeletal muscle of patients treated with casimersen; this approval is contingent on further verification in confirmatory trials. Amondys 45 is currently marketed under the tradename AMONDYS 45™ by Sarepta Therapeutics, Inc.

Trade Name Amondys 45
Availability Prescription only
Generic Casimersen
Casimersen Other Names Casimersen
Related Drugs deflazacort, Emflaza, Exondys 51, Amondys 45, Vyondys 53, eteplirsen
Weight 100mg/2ml,
Type Intravenous solution
Protein binding

Casimersen binding to human plasma proteins is not concentration-dependent, ranging from 8.4-31.6%.

Groups Approved, Investigational
Therapeutic Class
Available Country United States,
Last Updated: September 19, 2023 at 7:00 am
Amondys 45
Amondys 45


Amondys 45 is an antisense phosphorodiamidate morpholino oligonucleotide used to treat Duchenne muscular dystrophy patients with mutations amenable to exon 45 skipping.

Amondys 45 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients confirmed to have a DMD gene mutation amenable to exon 45 skipping. This indication represents an accelerated approval based on observed efficacy; continued approval for this indication may be contingent on the verification of safety and efficacy in a confirmatory trial.

Amondys 45 is also used to associated treatment for these conditions: Duchenne's Muscular Dystrophy (DMD)

How Amondys 45 works

Duchenne muscular dystrophy (DMD) is an X-linked recessive allelic disorder that results in the absence of functional dystrophin, a large protein comprising an N-terminal actin-binding domain, C-terminal β-dystroglycan-binding domain, and 24 internal spectrin-like repeats. Dystrophin is vital for normal muscle function; the absence of dystrophin leads to muscle membrane damage, extracellular leakage of creatinine kinase, calcium influx, and gradual replacement of normal muscle tissue with fibrous and adipose tissue over time. DMD shows a characteristic disease progression with early functional complaints related to abnormal gait, locomotion, and falls that remain relatively stable until around seven years of age. The disease then progresses rapidly to loss of independent ambulatory function, ventilatory insufficiency, and cardiomyopathy, with death typically occurring in the second or third decade of life.

The human DMD gene contains 79 exons spread over approximately 2.4 million nucleotides on the X chromosome. DMD is associated with a variety of underlying mutations, including exon duplications or deletions, as well as point mutations leading to nonsense translation through direct production of an in-frame stop codon, frameshift production of an in-frame stop codon, or aberrant inclusion of an intronic pseudo-exon with the concomitant production of an in-frame stop codon. In all cases, no functional dystrophin protein is produced. Becker muscular dystrophy (BMD) is a related condition with in-frame mutations that result in the production of a truncated but partially functional dystrophin protein. BMD patients, therefore, have milder symptoms, delayed disease progression, and longer life expectancy compared to DMD patients.

Amondys 45 is an antisense phosphorodiamidate morpholino oligonucleotide designed to bind to exon 45 of the DMD pre-mRNA and prevent its inclusion within the mature mRNA before translation. It is estimated that around 8% of DMD patients may benefit from exon 45 skipping, in which the exclusion of this exon results in the production of an internally truncated and at least partly functional dystrophin protein. Although fibrotic or fatty muscle tissue developed previously cannot be improved, this therapy aims to slow further disease progression through the production of partially functional dystrophin and alleviation of the pathogenic mechanism of muscle tissue necrosis.


Studies in male mice and rats suggest potential nephrotoxicity. Amondys 45 was administered weekly to male rats by IV injection for 12 weeks (0, 12, 120, or 960 mg/kg) or 22 weeks (0, 300, 960, or 2000 mg/kg) or by subcutaneous injection for 26 weeks (0, 300, 600, or 960 mg/kg). In the 12-week study, microscopic findings in the kidney (cytoplasmic basophilia and microvacuolation) were observed at the highest dose tested. In the 22- and 26-week studies, renal tubular degeneration was observed at all doses. Male rats administered casimersen (0, 250, 500, 1000, or 2000 mg/kg) intravenously for 13 weeks also experienced renal tubular degeneration at all tested doses, as well as microscopic changes accompanied by blood urea nitrogen increase at the highest tested dose. A no-effect dose for adverse effects on the kidneys was not identified in any of these studies. Plasma exposure (AUC) at the lowest dose tested in the 26-week study (300 mg/kg) was approximately two times that in humans at the recommended human dose (RHD) of 30 mg/kg/week, while exposure in the rat studies at the lowest dose was approximately four times that in humans.

Studies involving weekly administration in cynomolgus monkeys found similar tubular basophilia and microvacuolation at doses ≥40 mg/kg, which largely resolved by four weeks following the last dose. This study determined a no observed adverse effect level for repeated intravenous administration of 320 mg/kg.

Food Interaction

No interactions found.

Amondys 45 Disease Interaction

Moderate: renal impairment

Volume of Distribution

Amondys 45 administered at 30 mg/kg had a mean steady-state volume of distribution (%CV) of 367 mL/kg (28.9%).

Elimination Route

DMD patients receiving IV doses of 4-30 mg/kg/week revealed exposure in proportion to dose with no accumulation of casimersen in plasma with once-weekly dosing. Following a single IV dose, casimersen Cmax was reached by the end of infusion. Inter-subject variability, as measured by the coefficient of variation, ranged from 12-34% for Cmax and 16-34% for AUC.

Pre-clinical studies in nonhuman primates (cynomolgus monkeys) investigated the pharmacokinetics of once-weekly casimersen administered at doses of 5, 40, and 320 mg/kg. On days 1 and 78, the 5 mg/kg dose resulted in a Cmax of 19.5 ± 3.43 and 21.6 ± 5.60 μg/mL and an AUC0-t of 24.9 ± 5.17 and 26.9 ± 7.94 μg*hr/mL. The 40 mg/kg dose resulted in a Cmax of 208 ± 35.2 and 242 ± 71.1 μg/mL and an AUC0-t of 283 ± 68.5 and 320 ± 111 μg*hr/mL. Lastly, the 320 mg/kg dose resulted in a a Cmax of 1470 ± 88.1 and 1490 ± 221 μg/mL and an AUC0-t of 1960 ± 243 and 1930 ± 382 μg*hr/mL.

Half Life

Amondys 45 has an elimination half-life of 3.5 ± 0.4 hours.


Amondys 45 administered at 30 mg/kg has a plasma clearance of 180 mL/hr/kg.

Elimination Route

Amondys 45 is predominantly (more than 90%) excreted in the urine unchanged with negligible fecal excretion.

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