PTC Therapeutics‘ new investigational therapy ataluren shows promise for preserving lung function and slowing disease progression in non-ambulatory nonsense mutation Duchenne muscular dystrophy patients, according to a recent news release.
The results came from an analysis comparing lung function data from a PTC extension study (Study 019; NCT01557400) and data from a study evaluating the natural history of the disease (Cooperative International Neuromuscular Research Group; CINRG).
“We are excited to share the first results available from our long-term DMD (Duchenne muscular dystrophy) extension study in non-ambulatory patients,” said company CEO Stuart Peltz, PhD, in the release. “The potential for a therapy to slow disease progression and to improve outcomes beyond ambulation is significant for patients with nonsense mutation DMD.”
A nonsense mutation is an alteration in the genetic code that interferes with the synthesis of an essential protein, causing the protein to be incomplete and dysfunctional. In the case of DMD, the affected protein (dystrophin) is responsible for progressive muscular dysfunction. DMD also affects respiratory muscles and causes respiratory complications. For this reason, the measurement of lung function is associated with disease progression and mortality.
To analyze the possible benefits of ataluren, researchers evaluated the forced vital capacity (FVC) – a measure of respiratory insufficiency that accompanies the aging process – in 53 patients from Study 019. The FVC of those patients was then compared to measurements of 114 long-term DMD patients from the CINRG study, who had not received ataluren. To ensure the appropriate comparison, patients were matched according to several parameters that included non-ambulatory (requiring wheelchair use), age below or equal to 25 years, use of corticosteroids above or equal to 24 months.
The analysis indicated that in patients who did not receive ataluren, FVC peaked at an average 12.5 years and then declined. On the other hand, ataluren-treated patients had a peak FVC at an average age of 16.5 years – four years later than the control group. Overall, the absolute FVC was 13.8 percent higher in the treated patients compared to the control group.
The results suggest that ataluren brings about a beneficial effect in DMD patients by slowing the progression of lung dysfunction and allowing the restoration of functional dystrophin.
The drug has received conditional approval in Europe under the name Translarna, but it is still under evaluation in the United States. Several groups have supported the development of ataluren, including the Cystic Fibrosis Foundation Therapeutics, the Muscular Dystrophy Association, and the US Food and Drug Administration’s Office of Orphan Products Development.