Efficacy

Efficacy of Exondys 51 (Eteplirsen)

Exondys 51 (eteplirsen) is an antisense oligonucleotide designed for the treatment of Duchenne Muscular Dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. This medication aims to bind to exon 51 of dystrophin pre-mRNA, resulting in the exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. By allowing cells to produce an internally truncated but functional form of dystrophin protein, Exondys 51 offers a potential to slow the progression of DMD.

The approval of Exondys 51 was based on the increase in dystrophin production in skeletal muscle observed in some patients treated with the drug. However, the clinical benefit of Exondys 51, such as improvement in motor function or delay in disease progression, has not been definitively established. Clinical trials have shown variable efficacy, and the FDA has required a post-marketing study to confirm the drug's clinical benefit. The accelerated approval was granted based on the surrogate endpoint of dystrophin increase, with the understanding that continued approval may be contingent upon verification of clinical benefit in confirmatory trials.

Efficacy of Vyondys 53 (Golodirsen)

Vyondys 53 (golodirsen) is another antisense oligonucleotide indicated for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. Similar to Exondys 51, Vyondys 53 is designed to bind to exon 53 of dystrophin pre-mRNA, leading to exclusion of this exon during mRNA processing. This facilitates the production of an internally truncated but functional dystrophin protein, which is lacking in patients with DMD.

The efficacy of Vyondys 53 was evaluated based on the surrogate endpoint of dystrophin production in the muscles of patients who received the drug. The increase in dystrophin production was deemed reasonably likely to predict clinical benefit, leading to the drug's accelerated approval by the FDA. As with Exondys 51, the clinical benefit of Vyondys 53, including whether it improves motor function or delays disease progression, has not been fully demonstrated. The FDA has also mandated a post-marketing study to confirm the anticipated clinical benefit of Vyondys 53 in DMD patients.