In this Phase IIb Study in Duchenne Muscular Dystrophy, eteplirsen in two doses - 50mg/kg and 30mg/kg - were compared to placebo followed by eteplirsen. There was a significant improvement during the 6-minute walking test after 48-weeks' treatment among those on the higher dosage, when compared to the children on placebo.
The trial also showed that eteplirsen helped repair muscle tissue.
The boys on eteplirsen experienced an increase in dystrophin-positive fibers to 47% of normal after 48 weeks of treatment - the medication was administered once a week. The placebo-delayed cohort, the group of boys who were on placebo for 24 weeks and then on eteplirsen for the last 24 weeks also had a statistically significant improvement in dystrophin-positive fibers to 38.3% of normal.
Jerry Mendell, M.D., Director of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital and principal investigator of the Phase IIb study, said:
"These data represent a significant milestone and a defining moment of progress and hope for patients with DMD and their families, as well as for those of us in the scientific community who have been pursuing potential treatments for this devastating and deadly disease for decades.
By addressing the underlying cause of DMD, eteplirsen has demonstrated unparalleled effects on enabling dystrophin production and slowing the progression of the disease as measured by the 6-minute walk test, with no treatment associated adverse events. While eteplirsen is targeted to DMD patients with a specific genetic mutation, I think the implications for all DMD patients with related genetic mutations are clearly evident."
Eteplirsen is an exon-skipping compound - it skips the defective exon 51 of the dystrophine gene, allowing it to produce dystrophin protein from messenger RNA. Dystrohpin protects muscle fibers and membrane structures from deterioration.
50mg/kg eteplirsen gave an 89.4 meter advantageIn the 6-minute walking test, the children on 50mg/kg administered once a week for 48 weeks walked 89.4 meters more than those on 24 weeks placebo plus 24 weeks on eteplirsen.
At the beginning of the trial (baseline) the boys walked an average of 394.5 meters.
- The eteplirsen group - the boys on 50mg/kg over 48 weeks walked 21 meters further than at the beginning of their treatment
- The placebo-delayed- eteplirsen group- the boys on 24 weeks placebo followed by 50mg/kg for another 24 weeks walked 68.4 meters less than at the beginning of the treatment.
This means that those in the eteplirsen group had an 89.4 meter advantage over those in the placebo-delayed- eteplirsen group
Chris Garabedian, President and CEO of Sarepta Therapeutics, said:
"We are extremely excited about these data, as they demonstrate that longer-term treatment with eteplirsen is translating to continued and unprecedented increases in both dystrophin production and clinical benefit across various subgroups of DMD patients involved in this study. On a broader scale, these results signify the promise and tremendous potential of our RNA-based technology to impact and modulate disease at the genetic level, which may lead to first-ever opportunities to target serious and life-threatening rare conditions at the origin of disease."
Adverse events - throughout the 48 weeks of treatment, no adverse events related to the therapy were reported, neither were there any serious adverse events of any kind, and none of the patients discontinued. There were no clinically significant treatment-related changes on any of the safety lab parameters, such as renal function or various biomarkers.
Shares of Sarepta rose 123% in premarket trading on Wednesday morning to $33.40, a tripling in value since yesterday morning after the experimental medication showed how effective it was in improving walking ability.
What is Muscular Dystrophy?Muscular dystrophies (MD) are a group of genetic diseases in which there is progressive degeneration and weakness of voluntary or skeletal muscles - muscles which control movement. In some types of muscular dystrophy, the heart and other involuntary muscles are affected - other organs may be involved too.
Some forms of muscular dystrophy appear during infancy or childhood, while others may not become detectable until middle age or even later.
Duchenne Muscular Dystrophy (DMD) is the most common form of MD; it mainly affects boys. Muscles need dystrophin, a protein, to maintain their integrity. In patients with DMD, there is an absence of dystrophin. DMD usually starts when the boy is aged between 3 and 5 years; it progresses at a fast pace. By the time the boy is 12 he is usually unable to walk. Later on he will need a respirator in order to breathe properly.
Approximately 1 in every 3,500-5,000 boys is born with MD. In the USA, between 400 and 600 boys are born with MD every year. The sister of a boy with MD has a 50% chance of inheriting the faulty gene and passing it on to her own children.