Efficacy

Vyondys 53 (golodirsen) Overview

Vyondys 53 (golodirsen) is an antisense oligonucleotide approved by the FDA for the treatment of Duchenne Muscular Dystrophy (DMD) in patients with a confirmed mutation amenable to exon 53 skipping. DMD is a genetic disorder characterized by progressive muscle degeneration and weakness due to the absence of dystrophin, a protein necessary for muscle function. Golodirsen works by binding to exon 53 of the dystrophin pre-mRNA, resulting in the exclusion of this exon during mRNA processing. This allows for the production of an internally truncated, yet functional, dystrophin protein.

Efficacy of Vyondys 53 in DMD

The efficacy of Vyondys 53 was established on the basis of increased dystrophin production in the skeletal muscle of patients with DMD. In a clinical study, patients treated with golodirsen demonstrated a statistically significant increase in dystrophin levels as measured by Western blot, with a mean increase of 0.1% of normal compared to untreated patients. While this increase is modest, it is believed to be sufficient to provide a clinical benefit by slowing the progression of the disease. However, it is important to note that the clinical benefit of golodirsen has not been directly confirmed in controlled clinical trials, and the drug was approved under the FDA's accelerated approval pathway based on the surrogate endpoint of dystrophin increase.

Viltepso (viltolarsen) Overview

Similar to Vyondys 53, Viltepso (viltolarsen) is an antisense oligonucleotide indicated for the treatment of DMD in patients with genetic mutations amenable to exon 53 skipping. Viltolarsen is designed to bind to exon 53 of the dystrophin pre-mRNA, facilitating the production of a truncated but functional form of dystrophin protein. The approval of viltolarsen was also based on the surrogate endpoint of increased dystrophin production in the muscles of DMD patients.

Efficacy of Viltepso in DMD

The efficacy of Viltepso was evaluated in two clinical trials that demonstrated a significant increase in dystrophin production in patients with DMD. The trials measured dystrophin levels by Western blot and showed an increase from baseline in dystrophin levels, with a mean increase of 6% of normal levels after 20 to 24 weeks of treatment. This level of dystrophin production is thought to be clinically meaningful, as it may slow the progression of the disease. However, as with golodirsen, the clinical benefit of viltolarsen in improving motor function or slowing disease progression has not been definitively established in controlled trials, and Viltepso was also approved under the FDA's accelerated approval pathway.