Prospects for approval of Sarepta Therapeutics’ Duchenne muscular dystrophy (DMD) treatment eteplirsen seem to be diminishing as the FDA casts doubt on the biomarker and endpoints used in clinical trials.
The company has suggested the US regulator may ask for more information on eteplirsen and that a marketing application for the drug at this juncture would be “premature”.
The FDA’s position has been influenced by GlaxoSmithKline and Prosensa’s disappointing phase III trial results with the DMD candidate drisapersen, which like eteplirsen is said to work via a process called ‘exon skipping’, producing a semi-functional version of the dystrophin protein that is abnormal in DMD.
Sarepta also indicated that “recent natural history data in DMD – combined with the drisapersen results – raise “considerable doubt” about both the dystrophin biomarker and the supportive clinical efficacy assessed on the 6-minute walk test (6MWT) in its phase IIb trial of eteplirsen.
The agency reportedly would like to see clinical data showing that DMD patients are stabilised over a two-year period when treated with eteplirsen, with the addition of a placebo control which Sarepta believes would double the size of its planned confirmatory study.
It also pointed to previous negative results with PTC Therapeutics’ PTC124, another drug thought to function by increasing functional dystrophin levels.
Shares in the company went into free-fall on the news, losing 46 per cent of their value yesterday and completely negating any gains made for the stock since the start of the year.
“We are very disappointed with the FDA’s decision to reconsider their openness to a potential NDA filing based on our current data,” said Chris Garabedian, Sarepta’s chief executive, adding that the company’s 96 weeks six-minute walk test data presented last month “is not typical of what has been characterised in the broader natural history literature and in clinical studies.”
“We strongly believe in the potential of eteplirsen to address a serious unmet medical need in DMD and we are committed to its development,” he added.
Sarepta also reported its third-quarter financial results yesterday, posting an operating loss of $21.3m on revenues of $4.2m. The company raised $125m by offering new shares in the quarter and ended the period with cash reserves of around $280m.