Initial results of the study will be the subject of a poster presentation at the 2018 Annual Meeting of the American Academy of Neurology (AAN), taking place April 21-27 in Los Angeles. The presentation is titled “Tolerability of Eteplirsen for Duchenne Muscular Dystrophy in the Youngest Reported Patient Treated With This Therapy,” and will be presented in the session Child Neurology and Developmental Neurology: Neuromuscular Disease.
DMD is characterized by reduced levels of the dystrophin protein due to genetic mutations affecting its coding gene DMD. Several mutations in different parts of the gene have been linked to this disease.
Sarepta Therapeutics developed Exondys 51 to restore dystrophin levels in patients that have mutations amenable to exon 51 skipping, which represents about 13% of DMD patients. In September 2016, Exondys 51 was approved by the U.S. Food and Drug Administration, becoming the first therapy available to specifically treat DMD.
During clinical trials, Exondys 51 was only tested in children older than 4. As a result, there is limited information on the safety, tolerability, and effectiveness of the therapy in younger children.
“With availability of eteplirsen commercially, early diagnosis and therapy initiation for pre-symptomatic patients would theoretically afford benefit in delaying symptoms and preserving ambulation,” the researchers wrote.
In this study, researchers at the University of Louisville reviewed preliminary clinical data of an infant with confirmed DMD who started treatment with Exondys 51 at 10 months old.
The patient had a family history of DMD, with an affected uncle and the mother who was a carrier of a DMD mutation. At 5 months old, the infant had very high creatine kinase levels, and genetic testing confirmed a DMD deletion from exon 48 to 50, which could be overcome by exon 51 skipping with Exondys 51. Treatment was started with a weekly dose of 30 mg/kg.
Assessment of the infant’s clinical status after six months of treatment showed that the child had almost two times less creatine kinase than before beginning the therapy. All vital signs, kidney and heart function, and blood parameters were normal. Liver function was increased before the treatment and remained stable during the six months of follow-up.
Evaluation of the infant’s development by the Bayley scale showed that, after six months of treatment, the child was in the 4th percentile for motor assessment.
These results show that, to date, treatment with Exondys 51 has not caused any adverse effects in the infant and that the treatment was well-tolerated. “Effect of early therapy on efficacy will be determined based on continued longitudinal follow up,” the researchers said.