Ractigen Therapeutics has announced that its investigational small activating RNA (saRNA) therapy, RAG-18, has received Orphan Drug Designation (ODD) from the FDA for the treatment of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). This designation underscores the potential of RAG-18 to address the unmet medical needs of patients with these rare genetic disorders.
Mechanism of Action
RAG-18 is designed to target and activate the UTRN gene in muscle cells, which leads to increased production of utrophin. Utrophin is structurally and functionally similar to dystrophin, the protein that is deficient in individuals with DMD. By upregulating utrophin expression, RAG-18 aims to provide a functional substitute for the missing dystrophin, potentially alleviating the symptoms and progression of the disease. The therapy utilizes Ractigen's RNA activation (RNAa) platform, which enhances endogenous gene expression through targeted saRNAs.
Preclinical Evidence
Preclinical research, including data presented at the 2023 Oligonucleotide Therapeutics Society (OTS) meeting, demonstrated that RAG-18 can effectively induce utrophin mRNA and protein expression in skeletal muscle-derived cell lines. Furthermore, studies in a mouse model of DMD (hUTRNp KI/KI x MDX mice) showed that RAG-18 treatment ameliorated muscle damage. These findings suggest that RAG-18 could represent a novel therapeutic strategy for DMD and BMD, regardless of the specific mutation in the DMD gene.
Clinical Development and Pipeline
Ractigen's pipeline includes other saRNA therapies, with RAG-01 being the most advanced. RAG-01 is currently in a phase 1 clinical trial for non-muscle invasive bladder cancer (NMIBC), where it aims to activate a tumor suppressor gene silenced in bladder cancer cells.
Significance of Orphan Drug Designation
The FDA's Orphan Drug Designation provides Ractigen with several benefits, including potential tax credits for qualified clinical trials, exemption from user fees, and eligibility for seven years of market exclusivity upon approval. This designation, combined with the previous Rare Pediatric Disease Designation, highlights the importance of RAG-18 as a potential treatment for DMD and BMD. According to the National Library of Medicine, DMD has a prevalence of 2 per 10,000 individuals in the United States, while BMD has a prevalence of 0.26 per 10,000 male individuals.
Executive Perspective
"Receiving FDA ODD marks a pivotal achievement for RAG-18," said Long-Cheng Li, MD, founder and CEO of Ractigen Therapeutics. "Combined with the recent rare pediatric disease designation, it reflects the groundbreaking work we’re doing with RNAa and reinforces our commitment to making a real difference in the lives of those affected by rare diseases. This recognition fuels our determination to push forward with RAG-18’s development, aiming to bring innovative and life-changing treatments to DMD and BMD patients around the world."
