PTC Therapeutics has announced new data supporting the potential benefit of ataluren in preserving lung function in patients with nonambulatory nonsense-mutation Duchenne muscular dystrophy (nmDMD). The results were based on analyses of lung function data from one of the company’s ongoing open-label extension studies compared with natural history data from a comparable nonambulatory cohort.

Ataluren is a protein-restoration therapy designed to facilitate the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation. A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. The resulting disorder is determined by which protein cannot be expressed in its entirety and is no longer functional, such as dystrophin in DMD. Ataluren is an investigational drug in the United States.

Patients with DMD experience progressive dysfunction of respiratory muscles––in particular, the diaphragm––leading to respiratory failure, which is the primary cause of death in persons with the disease. Pulmonary function in DMD patients has historically been assessed using forced vital capacity (FVC), a measure of lung function that correlates with disease progression and mortality. FVC tends to peak at an earlier age in DMD patients and to decline more rapidly than in healthy individuals.

In the new analysis, the effect of ataluren on the preservation of lung function was based on FVC. The results were from a preliminary assessment of pulmonary function in 53 nonambulatory patients. These data were compared with findings from an external control group of 114 patients not receiving ataluren in a long-term DMD natural history study conducted by the Cooperative International Neuromuscular Research Group (CINRG). The CINRG cohort was matched using the following criteria: nonambulatory (requiring wheelchair use); not older than 25 years of age; and at least 24 months of corticosteroid use. Only CINRG data from 2012 onward were included.

In the untreated natural history cohort, FVC peaked at a mean age of 12.5 years and then declined thereafter. In comparison, ataluren-treated patients achieved peak FVC at a mean age of 16.5 years. In addition, the absolute FVC was 13.8% higher in ataluren-treated patients compared with untreated patients (P = 0.005), which suggested a slower progression in the loss of lung function in ataluren-treated patients.

Primarily affecting males, DMD is a progressive muscle disorder caused by the lack of functional dystrophin protein. Dystrophin is critical to the structural stability of skeletal, diaphragm, and heart muscles. Patients with DMD lose the ability to walk in their early teens and experience life-threatening lung and heart complications in their late teens and 20s. It is estimated that nonsense mutations account for approximately 13% of DMD cases.

Source: PTC Therapeutics, October 6, 2016.