ICER posts damning report on Sarepta’s Duchenne drug Exondys 51

Controversy has dogged Sarepta’s Duchenne muscular dystrophy therapy Exondys 51 since its approval, and it’s not out of the woods yet.

US cost-effectiveness watchdog the Institute for Clinical and Economic Review (ICER) has published a draft report that not only suggests Sarepta’s exon-skipping drug is too expensive, but also that its efficacy data is unconvincing.

Exondys 51 (eteplirsen) was given a conditional approval by the FDA back in 2017, to the delight of patients with DMD and their families, even though the agency’s own expert advisers had recommended rejecting it because of concerns that its clinical trials did not clearly demonstrate efficacy.

The drug was cleared to treat DMD patients amenable to exon 51 skipping – a group which represents about 13% of the population with the rare muscle-wasting disease.

“For eteplirsen, at its current price, no plausible treatment effects were found to make this treatment reach cost-effectiveness thresholds,” said ICER in its report.

Exondys 51 was priced at $300,000 per patient per year at launch and despite the controversy about its efficacy it has grown steadily to reach sales of $87 million in the first three months of this year.

ICER also expects the same will be the case for Sarepta’s follow-up drug golodirsen “if it is priced similar to eteplirsen.” Golodirsen – an exon 53-skipping agent – is heading for an FDA verdict in the summer and if approved would be suitable for around 8% of DMD patients.

One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 - 5,000 male births worldwide.

European regulators did not give their blessing to Exondys 51, but have licensed a rival exon-skipping therapy from PTC Therapeutics called Translarna (ataluren) – which failed to win a green light from the FDA.

Sarepta has decided to add to its exon-skipping approach in DMD with a foray into gene therapy, in the hope of developing a one-shot therapy for the disorder. Phase 1 results in 18 patients with its microdystrophin gene therapy candidate for DMD were reported in March.

Exondys 51 wasn’t alone in falling foul of ICER’s first-ever assessment of DMD drugs.

The group also took issue with PTC Therapeutics' new steroid drug Emflaza (deflazacort), which has a list price of $90,700, and concluded that when compared to prednisone, deflazacort “is projected to have very high costs relative to its benefits for patients and families.”

The costs were well above the acceptable threshold of $150,000 per quality-adjusted life year (QALY), and exceeded $500,000 in 95% of simulations, according to ICER’s analysis. It said that along with eteplirsen and golodirsen, the evidence supporting Emflaza remains “sparse.”

It’s worth noting that ICER’s report is only preliminary, and it is taking public comments on its conclusions until 18 June.