Modalis Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) designation to MDL-101 for the treatment of congenital muscular dystrophy type 1a (LAMA2-CMD). This designation highlights the potential of MDL-101, a novel precision medicine, to address a critical unmet need in children affected by this severe genetic disorder.
Addressing LAMA2-CMD with CRISPR-GNDM
LAMA2-CMD is a debilitating condition caused by the absence of the LAMA2 protein, essential for muscle fiber stability. Current treatment strategies focus on managing the symptoms, as there are no therapies available that target the underlying cause. Conventional gene therapy approaches are challenging due to the large size of the LAMA2 gene, which exceeds the capacity of adeno-associated virus (AAV) vectors.
MDL-101 leverages Modalis' proprietary CRISPR-GNDM® technology, enabling precise modulation of gene expression without inducing double-strand DNA breaks. This innovative approach aims to upregulate the expression of the LAMA1 gene, a sister gene to LAMA2, in muscle tissues. By compensating for the deficient function of LAMA2, MDL-101 has the potential to provide a durable, one-time treatment for individuals with LAMA2-CMD.
Significance of Rare Pediatric Disease Designation
The FDA grants RPD designation to therapies targeting serious or life-threatening diseases that primarily affect children under 18 years old and impact fewer than 200,000 people in the U.S. If MDL-101 receives marketing approval, Modalis Therapeutics may be awarded a Priority Review Voucher (PRV), which can be redeemed for expedited FDA review of another product. Modalis has also submitted an Orphan Drug application for MDL-101, currently under FDA review, which could provide benefits such as tax credits and market exclusivity.
Preclinical Evidence and Future Development
Preclinical data published on bioRxiv demonstrated that MDL-101 exhibited durability, efficacy, and a favorable safety profile in both mouse models and non-human primates. In mouse models, a single administration of the AAV vector encoding MDL-101 led to significant upregulation and phenotypic improvement of the LAMA1 gene. Furthermore, the expression of the GNDM gene and activation of the LAMA1 gene persisted beyond one year, despite immune recognition of the GNDM protein. Studies in juvenile non-human primates showed promising pharmacodynamics and a good safety profile.
Modalis Therapeutics anticipates filing an investigational new drug (IND) application for MDL-101 in 2025, marking a significant step toward clinical trials. "We have received many requests for our efforts from children and families around the world suffering from this disease for which there is currently no treatment, and we feel a mission to respond to the expectations of patients who are eagerly awaiting the start of clinical trials as soon as possible," said Haru Morita, CEO of Modalis.
