Study of Potential Therapy for Congenital Muscular Dystrophy Gets Boost from FDA

Margarida Azevedo, MSc avatar

by Margarida Azevedo, MSc |

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Santhera Pharmaceuticals announced that it has received a $246,000 grant from the U.S. Food and Drug Administration (FDA) to support its ongoing Phase 1 clinical trial evaluating omigapil as a potential treatment for children and adolescents with congenital muscular dystrophy (CMD).

The study, called CALLISTO (NCT01805024), is assessing the pharmacokinetics, safety, and tolerability of omigapil in ambulatory and non-ambulatory children, ages 5–16, with either of two CMD subtypes (COL6-RD or LAMA2-RD). About 20 eligible patients are currently being recruited; more information is available on the study’s clinical website.

“We are delighted that the FDA has awarded us this prestigious and highly competitive grant in support of our CALLISTO trial in CMD,” Thomas Meier, Ph.D., chief executive officer of Santhera, said in a press release. “With this award the FDA emphasizes the need for a therapy for CMD and the contribution of the CALLISTO trial to the development of an effective treatment.”

Severe forms of CMD can cause life-threatening progressive muscle weakness, known as floppy infant syndrome. A contributing factor for disease progression is apoptosis, or cell death, through a cascade of cellular events involving the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) pathways for the transcription of pro-apoptotic genes.

CMD is a clinically distinct group of inherited neuromuscular diseases that manifests with an early onset of symptoms that include weakness, contractures, elevated creatine kinase levels, an inability to stand or walk, eating difficulties, and respiratory insufficiency.

Omigapil is a deprenyl-analog with anti-apoptotic properties that binds to GAPDH. This interaction leads to its inhibition, and is thought to underlie the compound’s observed anti-apoptotic effect. In animal models of CMD, omigapil was seen to prevent cell death, reduce body weight loss and skeletal deformation, and to improve locomotive activity.

The proposed treatment was given Fast Track designation by the FDA for the treatment of CMD in May, and has previously been granted Orphan Drug Designation for the same indication in Europe and the United States. Santhera’s grant award came from the FEA’s Office of Orphan Products Development.

“As the leading organization representing the interests of patients with CMD, we are very pleased that the FDA recognizes the need to advance medical research in this orphan disease. With currently no effective treatment available for patients, the CALLISTO trial offers hope to patients with this devastating disease,” said Patrick May, CureCMD’s president.

The trial is being conducted in collaboration with the U.S. National Institutes of Health (NIH) under the leadership of Professor Carsten Bönnemann and Dr. Reghan Foley, with the National Institute of Neurological Disorders and Stroke (NINDS). Study completion is expected in early 2017.

Omigapil was developed by Novartis, and Santhera holds an exclusive worldwide license for its development as a treatment for congenital muscular dystrophy.