Amondys 45
casimersen · DMD exon 45 (PMO)In vitro only: human rhabdomyosarcoma cells and normal primary myoblasts
Exondys 51: animal efficacy model or human cells?
eteplirsen · DMD exon 51 (PMO)
Efficacy evidence
Exon 51 skipping in human muscle cell cultures, DMD patient muscle explants, transgenic hDMD mice (IM) and cynomolgus monkey (IV)
“The ability of eteplirsen to induce exon 51 skipping in human dystrophin mRNA has been demonstrated in the following: human muscle cell cultures; muscle explants from a DMD patient; gastrocnemius muscle of transgenic hDMD mice (after direct IM injection); quadriceps muscle, heart, and diaphragm of cynomolgus monkey (after 12 weeks of once weekly IV infusions); and EDB muscle of 7 DMD patients (after direct IM injection).”
Why that model
Human product cannot be tested in mdx mouse (different dystrophin mutation), requiring a mouse-specific exon 23 PMO
“For mdx mouse, the pharmacological activity of the human product cannot be tested because of differences in the dystrophin gene mutation, requiring use of a mouse-specific PMO, exon 23 skipping AON and, therefore, resulting in a different truncated dystrophin.”
Reviewer's view of the efficacy data
Supportive: greater than dose-proportional exon 51 skipping in monkey and dose-related mdx muscle pathology improvement with surrogate AVI-4225
“The sponsor’s studies demonstrate a greater than dose-proportional increase in exon 51 skipping with eteplirsen in monkey and a dose-related improvement in muscle pathology with a mouse-specific surrogate (AVI-4225) in the mdx mouse.”
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