Baliforsen

Thornton CA, et al. Lancet Neurol, 2023, 22(3), 218-228.

Baliforsen is an ASO designed to target the myotonic dystrophy protein kinase (DMPK) mRNA implicated in myotonic dystrophy type 1 (DM1). This condition, resulting from an RNA gain-of-function mutation, leads to toxic RNA accumulation, making DMPK mRNA suppression a pivotal therapeutic strategy.
In a completed phase 1/2a dose-escalation trial, baliforsen was evaluated for its safety and pharmacokinetics. Adult patients with DM1 received subcutaneous doses ranging from 100 to 600 mg over 36 days. The primary outcome was safety, assessed through treatment-emergent adverse events (TEAEs). The study found baliforsen to be generally well tolerated. Among 38 participants treated with baliforsen, 95% reported TEAEs, with the most common being injection-site reactions, headache (26%), contusion (18%), and nausea (16%). These events were mild in 86% of cases, with one participant in the 600 mg group experiencing transient thrombocytopenia. Baliforsen concentrations in skeletal muscle increased with dosage but remained below levels required for substantial target reduction, highlighting challenges in drug delivery efficiency.