- Touting how large their phase III clinical trials will be
- Only presenting data from the previously reported phase II study
- 6MWD was the primary endpoint at 24 weeks – continuous dose was statistically & clinically significantly greater 6MWD than placebo, but at 48 weeks, still clinically significant, but not statistically significant.
- Patients younger than Sarepta trial at entry, mix of patients under 7 & over 7.
- Multiple secondary endpoint measures of efficacy trending in right direction, but not statistically significant.
- Says drug was relatively well tolerated but had a few SAEs, but resolved over time & no patients dropped out due to them.
- 12 patient extension study Prosensa did that has gone on for ~4 years
- 2 patients not included in 6MWD test data – 1 lost ambulation quickly, 1 had a fractured bone → interestingly, a patient in Sarepta’s trial also had a bone break, and has recovered, which is impressive, and will participate in future 6MWT.
- 2 patients lost ambulation over the duration of the trial, it looked like around 60 weeks, but difficult to see on slide.
- Other 8 patients looked relatively stable.
- Can dose to much higher levels without toxicity – up to 50 mg/kg compared to Prosensa 6 mg/kg, and no problems dosing continuously (Prosensa/GSK also tried intermittent dosing, which appeared much less efficacious)
- Dystrophin takes 12 to 24 weeks to be produced (based on 24 different sections of a muscle biopsy)
- It is at this point that they start to see clinical benefits
- Showed that exon skipping is occurring → truncated product produced
- Showed that exon-skipped product is able to behave like normal dystrophin → dystroglycan complex.
- Highlighted Dr. Temple’s point that the treatment effect is more important than the number of patients, if you can see a clinical and statistically significant benefit.
- 6/6 patients who have been receiving eteplirsen for 84 weeks are stable
- 4/4 placebo patients who initially declined over the first 36 weeks (received eteplirsen starting week 24) stabilized for 48 weeks
- Discussed getting class approval, after doing clinical trials for 3 more exons after exon 51 → establishing dystrophin biopsy IF as surrogate endpoint will help speed up these future trials.
- Say they would like to see GSK separate data for patients 7 years, to look in population that is on the precipice of decline.
Zwerp, the fractured bones are likely a collateral effect of the steroids regime.
Weight gain, abnormal hair growth, sub-nomal height growth, ... are other side effects.
Steroids also likely delay the onset of ambulation loss, according to studies..