An overview of recent US-approved gene therapies for Duchenne muscular dystrophy and their respective clinical development programs

AbstractThere is no current cure for Duchenne muscular dystrophy (DMD), a rare genetic disease in young male patients, and the aim of treatment is to delay disease progression. Recent advancements in gene therapy provide potential improvement in targeting the underlying cause of DMD. Since 2016, the US FDA has approved four new antisense oligonucleotides for the treatment of DMD that are designed to achieve the stated objective and attenuate disease symptoms. They were registered via the accelerated pathway due to the life-threatening nature of the disease, unmet medical need, and possession of a unique mechanism of action. They partially overcome genetic mutations that hinder the production of dystrophin, a critical protein in maintaining muscle functions, via an exon skipping technology. Known as a phosphorodiamidate morpholino oligomer (PMO), eteplirsen facilitates the skipping of exon 51, golodirsen and viltolarsen effect similar action on exon 53, and casimersen performs similar function on exon 45. Following up to 1  year of therapy of these PMOs in DMD patients, dystrophin levels increased from baseline levels, which provided the necessary proof for the FDA’s interim approvals. To date, the safety results of these compounds also support the safe use of these PMOs in humans. Several long-term phase III defin itive clinical studies of each of the four compounds are currently ongoing in order to provide definitive proof of clinical safety and efficacy.
Source: Drugs and Therapy Perspectives - Category: Drugs & Pharmacology Source Type: research