The Food and Drug Administration (FDA) has approved Amondys 45™ (casimersen; Sarepta Therapeutics) for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed gene mutation amenable to exon 45 skipping. This is the first FDA-approved targeted treatment for patients with this rare DMD mutation.

Casimersen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer subclass that works by binding to exon 45 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing. Exon skipping allows for the production of an internally truncated but functional dystrophin protein.

The approval is supported by data from the ongoing ESSENCE trial (ClinicalTrials.gov:  NCT02500381), a double-blind, placebo-controlled phase 3 study that evaluated the efficacy and safety of casimersen and golodirsen in DMD patients amenable to skipping exons 45 or 53, respectively. Patients (N=43), all males aged 7-20 years with genetically confirmed mutation of the DMD gene that is amenable to exon 45 skipping, were randomized to receive either casimersen injection (30mg/kg) or placebo.

Initial study analysis showed that treatment with casimersen led to a statistically significant increase in dystrophin production in skeletal muscle from baseline to week 48. The FDA concluded that the increase in dystrophin production is reasonably likely to predict clinical benefit in patients with DMD with a confirmed gene mutation amenable to exon 45 skipping. The ESSENCE trial is ongoing and expected to conclude in 2024.


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The most common adverse reactions reported in casimersen-treated patients included upper respiratory tract infections, cough, fever, headache, joint and throat pain. While not seen in clinical studies, kidney toxicity, including potentially fatal glomerulonephritis, has been observed in nonclinical studies and after administration of some antisense oligonucleotides. Kidney function should be monitored during treatment with Amondys 45.

Amondys 45 is supplied as a solution in 100mg/2mL single-dose vials and will be available immediately.

References

  1. FDA approves targeted treatment for rare Duchenne muscular dystrophy mutation. [press release]. February 25, 2021.
  2. Sarepta Therapeutics announces FDA approval of Amondys 45™ (casimersen) injection for the treatment of Duchenne muscular dystrophy (DMD) in patients amenable to skipping exon 45. [press release]. February 25, 2021.
  3. Amondys 45™. [package insert]. Cambridge, MA: Sarepta Therapeutics; 2021.