Uncertain Future for Duchenne Gene Therapy as Confirmatory Trial Fails Primary Objective
Hope wavers for Duchenne gene therapy as confirmatory trial falls short of primary objective A setback for patients and families seeking to combat the debilitating effects of this rare disease, robbing children of mobility and causing premature mortality
Earlier this year, the conditional approval of the first gene therapy for Duchenne muscular dystrophy, a rare and debilitating disease, was seen as a significant milestone for patients and their families. It presented an opportunity to potentially slow down the progression of the disease, which not only limits the ability to walk by the teenage years but can also be fatal by the age of 30.
However, the drug known as Elevidys was only granted approval by the US Food and Drug Administration for children aged 4 and 5. This decision was based on the available evidence of its effectiveness. To ensure the drug remains available on the market and to expand its usage to older children who may be in more progressed stages of the disease, further research is needed.
Results from the study were released by Sarepta Therapeutics on Monday afternoon and were rather inconclusive. The trial did not meet its primary objective, which assesses the mobility of children. However, it did show success in several secondary measures.
A logo sign outside of the headquarters of Sarepta Therapeutics, Inc, in Cambridge, Massachusetts on February 21, 2018. (Photo by Kristoffer Tripplaar/Sipa USA)
Kris Tripplaar/Sipa USA/FILE
The CEO of the company, Doug Ingram, expressed hope that not only would the findings justify the drug's continued availability, but that they could also lead to its broader application.
"We will promptly request an update to broaden the labeled indication in order to treat all patients," Ingram stated in a press release, mentioning that Sarepta had already informed FDA leaders about the results. "After reviewing the data, the FDA has acknowledged their willingness to support this label expansion, based on the comprehensive evidence provided. They have expressed their intention to swiftly consider our submission for this matter."
However, Ingrams' optimism was not echoed by Wall Street investors, as Sarepta's stock experienced a 40% decline in value during Tuesday's trading.
Elevidys was cleared by the FDA in June due to evidence indicating that it enhances levels of dystrophin, a protein that functions as a muscle shock absorber. It is believed that higher levels of dystrophin can potentially lead to improved mobility, such as better walking abilities.
Sarepta has set the price for this one-time drug at $3.2 million, positioning it as the second most expensive medication globally. Other one-time gene therapies, which involve providing functioning copies of genes to compensate for disease-causing ones, especially for extremely rare conditions, have also exceeded the $3 million mark per patient. According to Johns Hopkins Medicine, Duchenne muscular dystrophy (DMD) affects approximately one in every 3,500 to 5,000 newborns, predominantly males due to its inheritance pattern.
The confirmatory trial aimed to improve the North Star Ambulatory Assessment (NSAA), which measures the physical abilities and movements of children, such as standing, walking, and other motor skills.
In the study involving children aged 4 to 7, it was found that one year after undergoing the gene therapy treatment, those in the treatment group showed an improvement of 2.6 points on the NSAA, compared to the placebo group's improvement of 1.9 points. However, this difference was not statistically significant, indicating that the study did not achieve its primary objective.
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Secondary measures achieved the desired outcomes in the study and were deemed statistically significant, such as the duration for children to rise or cover a distance of 10 meters while walking. The trial, referred to as EMBARK by the company, did not identify any additional safety concerns. During a conference call on Monday afternoon, Ingram informed analysts and investors that the company is currently preparing to submit its application to the FDA to broaden the drug's usage to encompass individuals of all ages and differing levels of mobility.
He affirmed that, in his viewpoint, the EMBARK results have fulfilled the criteria for substantial evidence of effectiveness. They validate Elevidys' mechanism of action and demonstrate its ability to change the disease progression in individuals with Duchenne.
