Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle disorder caused by pathogenic variants in the dystrophin gene that lead to absence or dysfunction of dystrophin and progressive muscle degeneration, loss of ambulation, and respiratory and cardiac complications. The disorder primarily affects males and is typically identified in early childhood with loss of ambulation often occurring by the early teenage years. Genetic testing is required to confirm the specific DMD gene variant for definitive diagnosis and variant location commonly clusters between exons 45 and 53 (for example, exon 51, 53, or 45).
Antisense oligonucleotides (short, synthetic, single-stranded oligodeoxynucleotides) act by selectively binding to specific exons of dystrophin pre‑mRNA to induce exon skipping, restore the reading frame, and produce an internally truncated but potentially functional dystrophin protein. Four antisense oligonucleotides discussed in this policy — eteplirsen (exon 51), golodirsen (exon 53), viltolarsen (exon 53), and casimersen (exon 45) — have received U.S. Food and Drug Administration approval under the accelerated approval pathway based on evidence of increased dystrophin production in skeletal muscle.
Because these approvals were granted under the FDA accelerated approval regulations, sponsors are required to complete confirmatory trials to verify clinical benefit. Available trial data show increases in dystrophin protein levels for these agents, but the absolute amounts are small and the minimum dystrophin level required to produce meaningful clinical benefit is not established. For eteplirsen, golodirsen, viltolarsen, and casimersen, the clinical evidence to date is judged insufficient to demonstrate that the observed increases in dystrophin translate into improvements in net health outcomes; ongoing or pending confirmatory trials have been required to assess clinical benefit.
As of the policy date, evidence of a confirmed clinical benefit from treatment with these antisense oligonucleotides is insufficient, and BCBSRI does not consider them to have demonstrated improvement in net health outcomes for treatment of DMD.