The FDA has approved a new drug, Exondys 51, manufactured by Sarepta Therapeutics that targets exon 51 skipping. This makes Exondys 51 the first drug approved by the FDA for Duchenne muscular dystrophy. Although clear clinical benefit like improvement in motor function hasn’t been established, a demonstrable increase in the amount of functional dystrophin protein production has led the FDA to approve the drug. (1)

Duchenne muscular dystrophy is one of the commonest muscular dystrophies observed in children. The genetic basis of this disease is known to be a mutation in the DMD gene located on chromosome Xp21, which is inherited in an X-linked manner. However, a positive family history is not required for its occurrence, and spontaneous mutations have been reported in approximately one third cases. (2)

Duchenne Muscular Dystrophy: Prevalence

Duchenne muscular dystrophy is a very rare condition that occurs in 1 in 3,500 to 5,000 live male births and is rarely observed in females; therefore, the development of treatment options is limited. Lack of a sufficient number of patients makes it challenging to conduct large scale clinical trials. Mutations in the DMD gene cause the absence or disruption of the protein dystrophin which is found in skeletal muscles and some CNS neurons. Symptoms usually manifest at the age of 3 to 5 years. Delay in motor and speech development along with proximal muscle weakness and abnormal waddling gait may be taken as indications. (2)

Duchenne muscular dystrophy

Duchenne Muscular Dystrophy Treatment options and prognosis

Currently, there is no complete cure for Duchenne muscular dystrophy which is characterized by severe muscle wasting. Symptoms manifest early in life, and the patient is usually bound to a wheelchair by mid teens followed by death in 20s. Standard treatment involves the use of corticosteroids when the disease is still at the early ambulatory stage. Oral administration of prednisone (0.75 mg/kg) or deflazacort (0.9 mg/kg) is generally undertaken. Dystrophin gene replacement therapy, exon skipping therapy, and nonsense suppression therapy are a few of the treatments that are currently being extensively studied. Most of the above treatments are directed toward reducing the symptoms and improving the quality of life of the patient. (2, 3)

Exondys 51 approved by FDA 

Exons are the coding sequences of genes that are interspersed with introns to form a functional gene. Several exons and introns together form a gene. Exon skipping literally means skipping of an exon during the process of translation, which involves the formation of proteins. New molecular therapies are employing the targeted use of exon skipping to treat Duchenne muscular dystrophy. Nearly 13% of Duchenne muscular dystrophy patients have a mutation in the DMD gene that can be treated by exon 51 skipping. Thus, a functional dystrophin protein can be produced by skipping exon 51. (1)

FDA has clarified that it requires established clinical benefit in clinical trials by Sarepta, failing which it might cancel the approval of the drug.  Imbalance and vomiting were the commonest side effects noted by participants consuming Exondys 51 in the clinical trials conducted so far.

The accelerated approval pathway was used to approve this drug; this method is only used for drugs that may have significant benefits over the existing treatment for life-threatening conditions. Post-approval clinical trials confirming the efficacy of the drug are awaited from the company. (1)

                                                      Credit: Dr. Rachita on behalf of Borderless Access

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References Sources

  3. Mercuri E, Muntoni F. Muscular dystrophy: new challenges and review of the current clinical trials.