FDA Grants Rare Pediatric Disease Designation to MDL-101 for Congenital Muscle Dystrophy

The FDA granted rare pediatric disease (RPD) designation to MDL-101 (Modalis Therapeutics Corporation) for the treatment of congenital muscular dystrophy type 1a (LAMA2-CMD). MDL-101 is a proposed novel precision medicine that targets the LAMA1 gene, causing LAMA2.¹

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“We are pleased that the FDA has recognized our development efforts for the rare disease and granted us RPD designation. 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,” Haru Morita, CEO of Modalis, said in a news release. “This designation from the FDA is proof that our efforts are rational and achieving results, and we hope to further accelerate the development of this world's first product using the cutting-edge technology.”¹

In the company’s second quarter 2024 financial results, it indicated that the filing of the investigational new drug application will be pushed back to 2025 due to reallocation of resources from the business restructuring. Furthermore, data from bioRxiv showed that MDL-101 demonstrated durability, efficacy, and safety in mouse models and non-human primates.^2,3

In the single administration of the adeno-associated virus vector encoding, investigators found a significant upregulation and phenotype improvement of the LAMA1 gene in the mouse models. Additionally, they found that the expression of GNDM gene and activation of the LAMA1 gene persisted beyond the 1-year period for the analysis, despite immune recognition of the GNDM protein, according to the study authors. In the non-human primate models, investigators determined the administration provided promising pharmacodynamics and a good safety profile. The effects of pharmacodynamics for juvenile non-human primates were compared with adults during the study.⁴

“Preclinical data from mouse and monkey studies were published in a paper in May and reported at conferences in June and July,” Morita said in the news release. “The response to the results presented in the paper has been overwhelming, and we have received inquiries from patients suffering from LAMA2-CMD, their families, and their physicians from around the world to participate in the clinical trial.”²

According to the National Library of Medicine, LAMA-CMD is “characterized by neonatal profound hypotonia, poor spontaneous movements, and respiratory failure.” Currently, there is no treatment for the condition, but physicians can treat the physical manifestations for the disease.⁵

REFERENCES

1. Modalis Therapeutics: FDA Grants Rare Pediatric Disease Designation to MDL-101 for the Treatment of Congenital Muscular Dystrophy Type 1a (LAMA2-CMD). News release. Modalis Therapeutics. September 30, 2024. Accessed September 30, 2024. https://www.businesswire.com/news/home/20240929247973/en

2. Modalis Therapeutics Reports Operational Highlights and Second Quarter 2024 Financial Results. News release. Modalis Therapeutics. August 7, 2024. Accessed September 30, 2024. https://www.modalistx.com/cms/wp-content/uploads/2024/08/E20240807_Financials.pdf

3. Modalis Therapeutics Reports Data Supporting Development of a Transformative Epigenome Editing Therapeutic, MDL-101: a First-in-Class Epigenome Editing approach for the Treatment of LAMA2-deficient congenital muscular dystrophy (LAMA2-CMD). News release. Modalis Therapeutics. May 7, 2024. Accessed September 30, 2024. https://www.businesswire.com/news/home/20240506038609/en/

4. Qin Y, Akbulut T, Mandraju R, Connolly K, et al. Efficient and durable gene activation by Cas9-mediated epigenome editing in vivo. bioRxiv. May 5, 2024. doi:https://doi.org/10.1101/2024.05.03.592438.

5. Oliveira J, Parente Freixo J, Santos M, et al. LAMA2 Muscular Dystrophy. 2012 Jun 7 [Updated 2020 Sep 17]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK97333/