Sarepta turns new leverage point for aspiring biotechs


Add strategic communications to the list of consultants that biotechs should consider hiring when in the middle stages of clinical development. Sarepta Therapeutics’ extraordinary reversal of fortune came in part thanks to a sustained lobbying campaign that persuaded top US FDA officials that Exondys 51 works even as the staff scientists and outside experts argued that its benefit was unproven.

The activism of Duchenne muscular dystrophy patients and their families in achieving accelerated approval provides a template for other groups considering whether to submit on phase II data or instead take on the costs of a pivotal trial (see table). If they have not already, Bluebird Bio and Ultragenyx Pharmaceutical, to name two, may want to engage with their respective patient communities to help ease regulatory review.

Regulatory flexibility

Because of population size and unmet medical needs, regulators often authorise orphan drugs without the usual requirements of large randomised controlled trials that aim to demonstrate efficacy on hard outcome endpoints. Open-label and single-arm or crossover trials using biomarkers can sometimes win the day.

The question is, of course, how complete and robust the data need to be. And now Sarepta has shown with Exondys, known generically as eteplirsen, that disputed biomarker data from an uncontrolled analysis of a clinical trial is justification for approval, with a little push from a patient community and a willing ear at the top echelons of the agency (Sarepta, patients win – but what of regulatory oversight?, September 19, 2016).

This may give some comfort to a number of biotechs with projects in phase II that this data milestone could be sufficient for approval – but on the chance it might make a difference, they might want to consider encouraging the patient community to become more active. Billions of dollars in sales are in play, so companies active in the orphan space may be looking for a strategy that allows them to unlock this revenue stream as early as possible.

Top orphan drugs in phase II 
Project Company Condition Sales 2022 ($m)
LentiGlobin Bluebird Bio Beta thalassaemia 824
vosoritide Biomarin Achondroplasia 565
fitusiran Alnylam Haemophilia A & B 536
triheptanoin Ultragenyx Glucose transporter type-1 deficiency syndrome 418
SPK-CHM Spark Therapeutics Genetic choroideremia 411
sparsentan Retrophin Focal segmental glomerulosclerosis 285
SHP607 Shire Retinopathy of prematurity 184
BMN 270 Biomarin Haemophilia A 179
Camvia (maribavir) Shire Cytomegalovirus disease in patients with impaired cell mediated immunity deemed at risk 142
SHP610 Shire Mucopolysaccharidosis III, type A (Sanfilippo A syndrome) 83
Source: EvaluatePharma.

Following the lead

For example Bluebird’s gene therapy LentiGlobin, which holds a consensus sellside forecast of $822m, according to EvaluatePharma, has just 25 patients under clinical study in its most advanced indication, beta thalassemia, and all are receiving the experimental treatment. Beta thalassemia also affects children – key data are expected at the ASH meeting in December.

The same can be said of Ultragenyx’s triheptanoin, or UX007. This project has orphan designation in glucose transporter type-1 deficiency syndrome, which similarly starts affecting patients in the first few months of life. Phase II data are expected by the end of 2016.

Shire has three projects fitting this description, two of which are specific to diseases that manifest in children. These are SHP607 for retinopathy of prematurity, which missed its primary endpoint in one phase II trial but had positive effects on secondary measures, and SHP610 for Sanfilippo A syndrome.

And Biomarin, too, has a significant stake – vosoritide is specifically being tested in children with achondroplasia. This is not to say that any of these companies will copy Sarepta’s strategy, and indeed they could well go to the FDA and European Medicines Agency with incredibly compelling data.

But Sarepta has clearly shown followers a new point of leverage with regulators. Biotech executives will now have to consider whether to use it, and could come under pressure from investors to do so.

To contact the writer of this story email Jonathan Gardner in London at or follow @ByJonGardner on Twitter

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