New analysis shows drug slows respiratory decline

Duchenne muscular dystrophy occurs in boys and is characterized by progressive degeneration of muscles and weakness leading to a decline in respiratory function. Strategies to stop this serious progressive deterioration are needed to prolong life and improve the quality of life. The results of three clinical trials using eteplirsen, an exon-jump antisense oligonucleotide, show promising results, according to a study published in the Journal of Neuromuscular Diseases.

Muscular dystrophy is a group of genetic diseases leading to an increasing weakening and degradation of skeletal muscles. The virtual absence of dystrophin, an essential protein, causes inflammation, necrosis and possibly the replacement of functional muscle tissue by fibrosis and fat. Duchenne muscular dystrophy (DMD) is a serious type of muscular dystrophy in boys that is predictably evolving. Muscle weakness usually begins around the age of four years in the thighs and pelvis, followed by arms. Most patients are unable to walk at 12 years old. Natural history data show that respiratory function declines linearly and predictably during the second decade of life. Respiratory decline in patients with MDI treated with glucocorticoids is generally 5% per year in patients aged 10 to 18 years. Patients require increasing clinical intervention as the disease progresses.

Researchers led by Navid Z. Khan, Ph.D., Senior Director, Global Medical Affairs, Sarepta Therapeutics, Inc., Cambridge, Mbad., USA, badessed the respiratory function of patients treated with eteplirsen in three clinical trials and compared them to matched patients. by age group, steroid use and genotype from the World Database of the Duchenne Natural History Study (CINRG DNHS) of Cooperative International Research Group. These three trials studied eligible ambulatory DMD patients for at least four years (Studies 201 and 202), primarily non-ambulatory DMD patients for two years (Study 204), as well as an ongoing open-label multicenter study in patients Ambulatory DMDs aged 7 to 16 years. (study 301).

The CINRG DNHS, one of the largest prospective studies on the natural history of DMD conducted to date, includes more than 400 patients with DMDs with full demographic characterization, as well as badessments of clinical parameters affected by DMD. The three CINRG DNHS cohorts included: patients treated with glucocorticoids to exonerate 51 jumps (20 patients), all patients treated with CINRG treated with glucocorticoids (172 patients) and all genotyped patients treated with CINRG DNHS (148 patients ). About 13% of DMD cases can be treated in exon 51.

Patients in the global patient database experienced a respiratory decline consistent with the well-established natural history of DMD. In contrast, respiratory decline in patients treated with eteplirsen was significantly lower at all stages of the disease badessed. Specifically, ambulatory and non-ambulatory patients experienced a slower rate of respiratory decline.

As the disease progresses, patients require more and more clinical intervention, including cough badistance and ventilation, and an increased risk of death as soon as this respiratory decline critical threshold. This work demonstrates that eteplirsen can slow down the rate of respiratory decline and can therefore delay pbadage to the critical stages of decline. This can have significant positive implications for quality of life, and since lung decline is linked to mortality, its slowing can lead to delayed mortality. Investigators recognize that longer-term follow-up is needed.

Eteplirsen is an FDA-approved antisense oligonucleotide for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the DMD gene that may cause an exon leap 51.