Nippon Shinyaku takes on Sarepta

A new competitor enters the exon 53 skipping niche, and might well take it over.

US approval for Nippon Shinyaku’s Viltepso gives the 8% of Duchenne muscular dystrophy patients who have the right kind of mutation a second therapeutic option. The exon 53-skipper is now in direct competition with Sarepta’s Vyondys 53 – and a look at the clinical data on dystrophin production suggests that Viltepso has an edge.

That is, if you’re willing to accept the weight of a study in just 16 patients, only eight of whom received the approved dose of Viltepso. The trial makes the data on which Vyondys 53 was approved – in 25 patients – look like a model of rigour. A larger study looking at measures of motor performance is in the works, and until data from that appear it seems likely that pricing, which the Japanese group has yet to announce, will dictate which product sells best.

The phase I/II trials on which the two rival therapies were approved looked at the same efficacy measure: production of dystrophin protein in patents’ muscles, a surrogate for muscle function.

In its US trial Viltepso brought the levels of dystrophin in the eight patients given 80mg/kg up to 5.9% of normal after 24 weeks of treatment, a 5.3-point increase from baseline. Vyondys 53 could only manage an improvement of less than one percentage point – over twice as long a treatment period.

Battle of the Exon 53 skippers
Drug Viltepso 40mg/kg Viltepso 80mg/kg Vyondys 53 30mg/kg
Trial ID NCT02740972 NCT02310906
No of subjects 8 8 25
Treatment duration 24 weeks 48 weeks
Normal dystrophin levels achieved 5.7% 5.9% 1.0%
Change from baseline (pct points) - 5.3 0.9
Source: drug labels. 

Comparing data across trials is fraught with difficulty, and this is especially true when the patient populations are as minuscule as they are here. But that is the task facing paediatricians, until harder data arrive from the confirmatory trials that are ongoing for both drugs. 

Racer53 will enrol 74 patients amenable to exon 53 skipping who will be treated with Viltepso or placebo for 48 weeks, with the primary endpoint being the time to stand test. The Essence trial of Vyondys 53 is rather larger, at 222 patients, with a placebo-controlled portion and an open-label part. The primary endpoint is the six-minute walk test at week 96.

Essence is expected to read out in 2022, with Racer53 data coming two years later. 


The US approval of Viltepso on the strength of such tiny patient numbers is perhaps not too surprising after the controversy over Vyondys 53’s green light. Sarepta’s product was waved through by the FDA just four months after it had been rejected, and the decision to approve had been fiercely disputed within the agency (Internal FDA documents reveal a familiar story for Sarepta, January 22, 2020).

The sellside sees Viltepso outselling Vyondys 53 as soon as 2022, according to consensus forecasts from EvaluatePharma. Sarepta can probably view this with equanimity; with projections for its Duchenne’s gene therapy SRP-9001 outpacing those for its exon-skippers it might be the winner in this disorder in the long term anyway.

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