Sarepta Therapeutics has announced new pulmonary function data through week 120 from Study 202, a Phase IIb open-label extension study of eteplirsen in patients with Duchenne muscular dystrophy ( DMD ). Results through more than two years of treatment showed stable pulmonary function in the intent-to-treat ( ITT ) study population ( N=12 ). These data are consistent with previously reported 120-week clinical data showing a general stabilization of walking ability in Eteplirsen-treated patients evaluable on the 6-minute walk test ( 6MWT ).
Respiratory muscle function from baseline through week 120, as measured by maximum inspiratory and expiratory pressure ( MIP and MEP ), has shown a 14.6% mean increase in MIP and a 15.0% mean increase in MEP.
Analyses of MIP percent predicted ( MIP adjusted for weight ) and MEP percent predicted ( MEP adjusted for age ) have demonstrated a mean increase from 90.2% at baseline to 95.2% at week 120 in MIP percent predicted, and a slight mean increase from 79.3% at baseline to 79.6% at week 120 in MEP percent predicted.
In addition, there was a mean increase in forced vital capacity ( FVC ), a measure of lung volume, of 8.7% from baseline to week 120, and FVC percent predicted ( FVC adjusted for age and height ) was maintained above a mean of 90% through week 120, with 101% at baseline and 93% at week 120.
According to Jerry Mendell, of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital and principal investigator of the phase IIb study, the first sign of respiratory muscle weakness in DMD is often deterioration in MIP and MEP as patients approach and enter their early teen years.
As the muscles continue to weaken over the course of the disease, respiratory dysfunction requiring ventilation support can severely impact quality of life and respiratory failure is often a significant factor in patient mortality in the later stages of disease progression.
Results through week 120 for other exploratory efficacy endpoints, including timed function tests ( e.g., Gowers’ maneuver and timed 4-step test ) and the North Star Ambulatory Assessment have shown declines compared to baseline, though at potentially slower rates as compared to the limited available natural history data.
These endpoints are less well characterized in DMD patients than the 6MWT and pulmonary function tests and have more inter- and intra-patient variability, although they may be predictors of decline at various stages of this disease.
All patients evaluable on measures of ambulation ( modified Intent-to-Treat, or mITT population ) are still able to perform these tests with the exception of one patient who is no longer able to perform the Gowers’ maneuver.
Eteplirsen was well tolerated through week 120 and there were no reported clinically significant treatment-related adverse events and no treatment-related serious adverse events. In addition, there were no hospitalizations or discontinuations. ( Xagena )
Source: Sarepta Therapeutics, 2014