Amondys 45
casimersen · DMD exon 45 (PMO)In vitro only: human rhabdomyosarcoma cells and normal primary myoblasts
Viltepso: animal efficacy model or human cells?
viltolarsen · DMD exon 53 (PMO)
Efficacy evidence
DMD patient fibroblasts differentiated into myotubes: exon 53 skipping (EC50 0.63-2.3 µM) and dystrophin production
“Primary: In vitro proof-of-concept studies, conducted primarily in DMD patient fibroblasts differentiated into myotubes, demonstrated viltolarsen-induced exon 53 skipping (EC50 values of 0.63-0.90 µM and 2.3 µM) and production of dystrophin protein in cells from DMD patients with deletion of exons 45-52 and exons 48-52, respectively.”
Why that model
Viltolarsen not pharmacologically active in rodents; in vivo exon skipping assessed only in monkey toxicity studies
“In vivo assessment of exon 53 skipping was included in the 12- and 39-week toxicity studies in monkey; viltolarsen is not pharmacologically active in rodents.”
Reviewer's view of the efficacy data
Human relevance judged from human rhabdomyosarcoma cells (EC50 3.4-5.9 nM) and DMD patient-derived myoblasts (83.1% skipping, presumably truncated dystrophin)
“Potential effects in humans were evaluated in using isolated human rhabdomyosarcoma cells, in which the EC50 for exon 53 skipping by vitolarsen ranged from 3.4 to 5.9 nM. Additionally, 83.1% exon 53 skipping efficiency was observed 1 week after transfection of myoblasts derived from DMD patient fibroblasts with 10 uM vitolarsen, correlating with expression of a presumably truncated dystrophin protein.”
Same question, other oligonucleotides
Amvuttra
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Vyondys 53
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Wainua
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