Ractigen Garners Orphan Drug Designation for Muscular Dystrophy saRNA Therapy RAG-18
Notably, the therapy previously received rare pediatric disease designation from the FDA in July 2024.
Ractigen Therapeutics has received orphan drug designation (ODD) from the FDA for RAG-18, its investigational small activating RNA (saRNA) that is currently in preclinical development for the treatment of cases of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) caused by any mutation in the DMD gene.1
Notably, the therapy previously received a rare pediatric disease designation from the FDA in July 2024. According to Ractigen, it is the first saRNA therapy to receive both designations from the agency.
RAG-18 is intended to function through targeted activation of the UTRN gene in muscle cells, leading to increased production of utrophin, the protein encoded by UTRN. Because utrophin is structurally and functionally similar to dystrophin, the protein that is deficient in patients with DMD, it is expected that its upregulation will provide clinical benefit. The activation takes place through RNA activation (RNAa), Ractigen’s platform technology designed to enable increased expression of endogenous genes through the targeting of gene regulatory domains with saRNAs. RAG-18 was administered via subcutaneous injection in preclinical research with the use of the company’s lipid-conjugated oligonucleotide (LiCO) technology.
“Receiving FDA ODD marks a pivotal achievement for RAG-18,” Long-Cheng Li, MD, the founder and chief executive officer of Ractigen Therapeutics, said in a statement.1 “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.”
Ractigen presented cell line and mouse model data related to RAG-18 at the 2023 meeting of the Oligonucleotide Therapeutics Society (OTS), held October 22 to 25, in Barcelona, Spain.2 In skeletal muscle-derived cell lines, it was found that promoter-targeted saRNAs induced the expression of human utrophin mRNA and protein. Furthermore, lead saRNA candidates were evaluated for efficacy in a mouse model of DMD with knock-in of the human UTRN promoter (hUTRNp KI/KI x MDX mice), and the induction ability was validated in this model.
“In summary, our work provides initial evidence that saRNAs could be delivered to skeletal muscles and heart to activate endogenous utrophin gene,” first author Wei-Hsiang Lin and colleagues wrote in the poster presented at the conference.2 “Treatment of MDX mice bearing human UTRN promoter with a lead saRNA ameliorated muscle damage. Our approach could represent a novel and translatable therapeutic strategy for DMD and BMD caused by any mutation of the DMD gene.”
Ractigen’s pipeline includes a number of other saRNA therapies for various indications.3 The furthest along in development is RAG-01, which has entered a phase 1 clinical trial for the treatment of non-muscle invasive bladder cancer (NMIBC). It is intended to activate the expression of a relevant tumor suppressor gene that is usually silenced in bladder cancer cells.
“FDA investigational new drug (IND) application approval for RAG-01 is a major achievement for Ractigen and a significant advancement for saRNA technology worldwide,” Li said in April 2024, when the therapy received IND clearance in the United States.4 “This first-in-class saRNA therapy harnesses the power of RNAa to target the p21 gene, offering a promising new option for patients with limited treatment choices. This approval validates the potential of RAG-01 as a leading saRNA therapy and strengthens our position as innovators in RNA-based treatments.”
