Unfazed by failure, PTC Therapeutics to appeal negative EMA decision on its disaster prone Duchenne drug
PTC Therapeutics’ bid to expand the approval of its Duchenne muscular dystrophy drug in Europe has been unsuccessful. The New Jersey-based drugmaker is not known for taking no for an answer and will appeal the decision, it said on Friday.
The drug, ataluren, has a checkered past, littered with failed trials.
In Europe, the drug — branded as Translarna — was conditionally approved by the EMA in 2014 to treat patients aged 2 and older with DMD who are able to walk, just ahead of the readout of a late-stage study, which showed the drug had failed.
The EMA has now refused to back the drug’s use in non-ambulatory patients based on the fresh data provided by PTC. The company presented data from a study involving 94 patients with nonsense mutation DMD — of which 44 were non-ambulatory. The study was powered to assess the long-term safety of Translarna, but also investigated the effectiveness of the treatment in patients unable to walk, measuring changes in lung function, versus historical data, the EMA said.
The EMA concluded the data did not establish the drug’s balance of benefits and risks in non-ambulatory patients. “The fact that Translarna is handled by the body in a similar way in patients who can walk and those who cannot was not enough to confirm the effectiveness of Translarna in these patients. This is because patients unable to walk are at a more advanced stage of the disease and have reduced muscle mass and therefore the benefits of treatment may be different. The additional data from the study could also not confirm the benefit of Translarna in patients no longer able to walk because there were problems with the way data from the CINRG (historical data) database, which was used to indirectly compare the effects of Translarna, were selected and analysed,” the EMA said.
PTC, on Friday, said it planned to request a re-examination in the coming weeks and expects the review to last roughly 4 months. The company’s shares $PTCT slipped about 5% to $41 before the bell.
Under the conditional approval, the EMA assesses the drug’s approvability on an annual basis. As expectations that the EMA would rescind its backing grew after the failed Phase III trial, PTC was given a reprieve in 2016 when the regulator allowed the company to keep the drug on the market if an additional study confirmed its effect.
The study is designed to be a placebo-controlled, 18-month trial, followed by an 18-month extension study — with data was expected in 2021. But, in a filing posted in March this year, PTC acknowledged the study is running behind schedule, due to slower-than-expected enrollment, and that it has asked the EMA for an extension. Meanwhile, the company’s bid to convince the EMA to grant Translarna full approval, from conditional approval, has been denied.
In the United States, PTC has had little luck. The FDA spurned the drug twice, and when company asked for a third review — emboldened perhaps by Sarepta’s $SRPT DMD approval of Exondys 51, despite insufficient data — the US health agency refused to even take a look at their application. Then, employing a regulatory loophole in the FDA’s own laws, PTC filed its application “in protest” forcing the FDA to take yet another look. The third time was not a charm. By the third try, the drug had also failed a study in cystic fibrosis — giving the FDA further impetus to issue its third, decisive rejection. In the fourth quarter of 2018, PTC initiated a new trial in yet another bid to change the FDA’s mind — and expects to make its fourth NDA attempt next year.
PTC does, however, have another DMD drug on the US market. In 2017, the drugmaker shelled out $140 million to acquire a cheap, old steroid for DMD from Marathon Pharmaceuticals — a company that had weathered a tempest of criticism for the $89,000 annual price it had slapped on the steroid, deflazacort. Scores of parents had been importing the generic from the UK for around $1,000 a year, but when Marathon got it approved as an orphan drug for DMD in the United States, that door effectively closed. PTC inherited the scandal when it bought the drug, and in its attempt to silence critics, cut the price to $35,000 per year.
Lately, PTC has been working on other programs. Its oral spinal muscular atrophy drug — risdiplam — partnered with Roche is expected to mount a challenge to Biogen’s $BIIB Spinraza and Novartis’ $NVS gene therapy Zolgensma.
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