The U.S. Food and Drug Administration (FDA) has recently granted orphan drug and rare pediatric disease designations to multiple therapies aimed at treating Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), underscoring the urgent need for effective treatments for these debilitating conditions. These designations provide significant incentives for pharmaceutical companies to develop therapies for rare diseases affecting fewer than 200,000 people in the United States, offering benefits such as market exclusivity and fee waivers.
RAG-18: Activating Utrophin for DMD and BMD
Ractigen Therapeutics' RAG-18, a first-of-its-kind small activating RNA (RNAa) candidate, has received orphan drug designation for both DMD and BMD. RAG-18 is designed to specifically target and activate utrophin (UTRN) gene expression. Utrophin, located on chromosome 6, is a paralog of dystrophin, exhibiting significant structural and functional similarities. Activating utrophin expression represents a promising therapeutic strategy for DMD, particularly as utrophin-A, the major isoform in myofibers, is enriched in neuromuscular and myotendinous junctions of adult muscles and at the sarcolemma of regenerating myofibers.
Preclinical studies have demonstrated that RAG-18 effectively mitigates muscle damage through its RNAa mechanism. Long-Cheng Li, founder and CEO of Ractigen, stated that this designation, combined with the previous rare pediatric disease designation, "reflects the groundbreaking work we’re doing with RNA activation (RNAa) and reinforces our commitment to making a real difference in the lives of those affected by rare diseases."
DMD, caused by mutations in the dystrophin gene on the X chromosome, affects approximately 1 in 3500 to 1 in 6000 males. The median life expectancy for individuals with DMD is 26 years. BMD, a milder form of DMD, also results from dystrophin gene mutations, but currently, there are no FDA-approved drugs specifically for BMD.
Neu-REFIX Beta Glucan: An Immune-Modulating Food Supplement
Neu-REFIX Beta glucan, a food supplement produced in Japan, has also received both rare pediatric disease and orphan drug designations from the FDA for DMD treatment. This designation will facilitate clinical trials in the USA, building on preclinical and clinical studies conducted in Japan and India. Neu-REFIX Beta 1,3-1,6 glucan is an exo-polysaccharide derived from the N-163 strain of Aureobasidium Pullulans. It is available as an orally consumable, allergen-free food supplement.
Research indicates that Neu-REFIX possesses anti-inflammatory properties, potentially modifying the disease course in DMD. Studies have documented its safety and potential benefits, leading to further research into autoimmune diseases, multiple sclerosis, and psoriasis vulgaris. The journey started in 2009, and findings have been presented at conferences such as the Asian and Oceanian Myology Center- Japan Muscle Society joint conference (AOMC-JMS 2024).
NS-050/NCNP-03: Antisense Oligonucleotide Therapy
Nippon Shinyaku Co., Ltd. previously received rare pediatric disease designation for NS-050/NCNP-03, an antisense oligonucleotide being developed for DMD treatment. This therapy targets patients with confirmed gene mutations amenable to exon 50 skipping. NS-050/NCNP-03 works by skipping part of the genetic information of the dystrophin gene, producing a functional dystrophin protein with a slightly shorter chain length, which is expected to suppress muscle function deterioration.
DMD primarily affects males and results from a deficiency in the dystrophin protein. Nippon Shinyaku is preparing clinical trials of NS-050/NCNP-03 in patients with DMD in Japan and the United States.
These FDA designations highlight the ongoing efforts to develop innovative therapies for DMD and BMD, addressing significant unmet medical needs in these rare and devastating conditions. While some RNA treatments have received conditional approval based on read-through or exon-skipping strategies, their applicability is limited to a small percentage of patients, and their efficacy in dystrophin restoration has been controversial. The pursuit of novel approaches, such as utrophin activation and immune modulation, offers hope for more effective and broadly applicable treatments.
