- An experimental gene therapy helped four boys with Duchenne muscular dystrophy stand up, walk and climb stairs more quickly than normally would be expected, according to updated results from a small study presented Wednesday by Sarepta Therapeutics and Nationwide Children's Hospital.
- Those initial signs of functional improvement were supported by laboratory data which showed treatment with the gene therapy led to strong expression of a shortened version of the crucial protein that's missing or dysfunctional in people with DMD.
- "The encouraging results that we previously saw and reinforced in the fourth patient strengthen our resolve to rapidly move to a confirming trial," Sarepta CEO Doug Ingram said in an Oct. 3 statement. The biotech hopes to launch a registrational study of the therapy by the end of 2018.
Sarepta's results are early, and with data from only four treated boys, far from conclusive. Still, Wednesday's update allows for greater confidence in the potential of the experimental gene therapy to treat DMD.
Children with the inherited disorder — almost exclusively boys — lack a protein known as dystrophin that's vital to maintaining the strength of muscle fibers. Without adequate dystrophin production, individuals with DMD suffer from progressive muscle weakening that makes normal activities like walking and climbing stairs difficult. Most patients need to use wheelchairs by adolescence and the condition can eventually lead to life-threatening heart conditions.
Sarepta's gene therapy, which was developed at Nationwide, aims to treat DMD by delivering a truncated, or "micro," form of the dystrophin gene to spur production of functional protein.
Data presented in June dramatically raised expectations for the therapy, showing that, in three boys, treatment led to protein levels between 38% and 54% of normal. Average gene expression — measured by the percentage of muscle fibers positive for micro-dystrophin — surpassed 75%.
The fresh results presented Wednesday at the World Muscle Society's annual meeting improved on those findings and included data from a fourth boy.
Across all four, mean gene expression reached 81% while post-treatment biopsies showed micro-dystrophin levels averaged 74% versus normal using one measure, and nearly 96% using another. The higher averages were boosted in part by inclusion of the fourth boy, who responded strongly to treatment.
Importantly, no serious adverse events were reported and the initial functional tests supported the laboratory findings.
In a presentation, lead study investigator Jerry Mendell of Nationwide noted the results indicated the boys were "performing in a manner unexpected for the typical boy with DMD."
Joseph Schwartz, an analyst with the investment firm Leerink, also found the results encouraging, calling the expression levels "robust" in an Oct. 3 note to clients.
Investors, however, didn't appear to have a consistent reaction. Shares in Sarepta initially rose by 2% in value when markets opened Thursday, before see-sawing back and forth between negative and positive territory.
The mixed reaction may stem from the variation in results between the fourth patient and the three earlier patients. Results also showed three of the four experienced elevated levels of an enzyme called gamma-glutamyl transferase.
"While [patient] variability as well as enzyme elevations may make some investors cautious, we continue to believe that micro-dystrophin gene therapies are on track to offer significant benefit in DMD," Schwartz wrote.
Wednesday's update is also a positive step forward after a brief clinical hold was placed on the study by the Food and Drug Administration. The hold was lifted in September after Sarepta submitted plans to account for the trace levels of DNA fragments found in plasmids used for the study that had been flagged by the agency.
Next up for the therapy will be initiation of a larger study to confirm the initial findings.