Rare pediatric disease designation granted to LAMA2-CMD therapy
Modalis' MDL-101 aims to treat disease that mostly affects children
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The U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designation to MDL-101, an epigenetic editing therapy that Modalis Therapeutics is developing for LAMA2-related congenital muscular dystrophy (LAMA2-CMD) — a genetic condition that’s characterized by muscle wasting evident at birth or shortly thereafter.
This FDA status recognizes MDL-101 for its potential to offer clinical benefits in a serious or life-threatening disease that affects fewer than 200,000 people in the U.S., primarily children and adolescents younger than 18. If MDL-101 is approved, the company may receive a voucher for priority review of another therapy, which it could redeem or sell.
“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,” Haru Morita, CEO of Modalis, said in a company press release.
LAMA2-CMD, also called merosin-deficient congenital muscular dystrophy type 1A, is caused by mutations in LAMA2, a gene that provides instructions for producing part of two members of the laminin family of proteins, which are needed to connect muscle fibers to surrounding structures and keep them stable.
The mutations result in the weakening of the skeletal muscles used for movement. In early-onset disease, symptoms become apparent at birth or within the first months of life. Children often don’t develop the ability to walk and have difficulty speaking and breathing. They also may develop scoliosis, or a curved spine.
No therapies are available for LAMA2-related congenital muscular dystrophy
No therapeutic options have been developed to date to address the underlying cause of the disease. Further, gene therapy is not deemed feasible because the LAMA2 gene is too large to fit into a vector — usually a harmless, engineered virus — that can deliver it into cells in the body.
To overcome this limitation, Modalis developed MDL-101 using its CRISPR-based epigenetic editing technology. CRISPR is a molecular tool used to change or edit pieces of a cell’s DNA; epigenetics refers to changes in the way genes are switched on and off without changing the actual DNA sequence.
Unlike conventional editing, Modalis’ technology modifies a gene’s activity without changing a cell’s DNA sequence.
We have received many requests for our efforts from children and families around the world … 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.
Given as a single dose, MDL-101 is designed to reach muscle cells and increase the activity of LAMA1, a gene that produces a similar protein to LAMA2. This is expected to compensate for LAMA2 protein deficiency or absence and ease symptoms of LAMA2-CMD.
“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,” Morita said, adding that the company is “pleased that the FDA has recognized our development efforts for the rare disease and granted us RPD [rare pediatric disease] designation.”
Modalis also has filed for FDA orphan drug designation for MDL-101, which would offer additional benefits, such as fee waivers and seven years of market exclusivity if the therapy is approved. That application is now being reviewed by the FDA, according to the company.
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