An experimental gene therapy dramatically improved the ability of a young boy with Duchenne muscular dystrophy to rise from the ground and climb stairs, repeating and improving on results seen in three previous patients who received the treatment, which is being developed by Sarepta Therapeutics of Cambridge, Massachusetts.
“The cautionary note is this all has to be confirmed in a larger trial,” says Douglas Ingram, Sarepta’s president and chief executive. He says he hopes to meet with the Food and Drug Administration later this year in order to design a study that compares the gene therapy with a control group. “Our goal is to bring this therapy rapidly to patients around the world,” Ingram says.
The results are being presented at a meeting of the World Muscle Society in Mendoza, Argentina. The results were shared with me ahead of presentation.
Sarepta’s gene therapy uses a virus, a modified version of the adeno-associated virus, to insert a shortened version of the gene for a protein called dystrophin into patients’ cells. Dystrophin is missing in Duchenne patients, causing them to lose muscle tone, forcing them into wheelchairs, and killing them, often by early adulthood.
Sarepta had previously announced that in three boys, this approach led to levels of the new dystrophin (called microdystrophin, because the protein is smaller) that were 40% of normal based on a test called the Western blot. Much smaller elevations in dystrophin were the basis for the approval of Sarepta’s marketed drug, Exondys 51. More impressively, in the previous results, levels of creatinine kinase, a marker for how quickly muscle is being destroyed, dropped 87%. Those results have largely held up; the average drop in creatinine kinase is now 78%.
For the fourth patient, microdystrophin levels were 183% of normal using the measure previously used by the FDA; other measures yielded equally impressive results. Creatinine kinase levels dropped 95%. The time it took for the boy to rise up from the ground dropped from 4.1 seconds to 2.3 seconds. The time to climb four stairs went from 4.8 seconds to 2.2 seconds.
For the whole group of patients, time to rise improved 13%, time to climb 4 stairs improved 31%, and time to walk 100 meters improved 14%. The children’s score on the North Star Ambulatory Assessment, a 34-point scale, improved 6.5 points from the first time they were tested to the most recent.
Sarepta is taking an unusual approach by presenting data from each patient in such detail. It is also including videos of the boys in its presentations. Scientists like to say that data is not the plural of anecdote; this is getting close to sharing anecdotes, which could lead to missing larger patterns. Releasing data in this matter could also create the illusion that a company is leading a competitor when it isn’t— the competitor could be waiting for when all the data are in.
On the flip side, it’s difficult to keep these patient stories under wraps, which means investors can learn about them from social media. Even as biotechnology companies move into stunning new territory with gene therapy approaches, they are pushing the envelope on what is done in clinical trials, too.
Solid Biosciences and Pfizer are also working on gene therapies for Duchenne.