Shares in PTC Therapeutics declined as much as 20 percent Thursday after the company announced Phase III data showing that its oral protein restoration therapy Translarna (ataluren) failed to significantly improve the distance patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) could walk from baseline in a six-minute walk test (6MWT). Still, CEO Stuart Peltz said results from the ACT DMD trial "show Translarna's ability to change the course of DMD disease progression," adding that "the totality of the data from our two robust placebo-controlled studies across over 400 patients demonstrate a clinically relevant impact on patients' lives."
Peltz indicated the company would submit the data to regulators in the EU, where the drug obtained conditional approval last year for nmDMD patients aged five years and older, and complete itsrolling submission to the FDA by the end of the year.
The ACT DMD study included 228 patients with nmDMD aged from 7 to 16 years who were randomised to receive Translarna or placebo for 48 weeks. Besides the primary endpoint of change from baseline in the 6MWT, key secondary outcome measures were timed-function tests, including time to run or walk 10 meters and the time to ascend or descend four stairs.
In the overall intent-to-treat study population, Translarna-treated patients showed a non-significant 15-metre benefit over a placebo in the 6MWT. However, PTC Therapeutics said that in a pre-specified patient population of patients with a six-minute walk distance of 300 metres to 400 metres, Translarna provided a "highly significant" benefit of 47 metres versus placebo, which the company noted is in line with prior experience in its Phase IIb trial. Moreover, no patients in the pre-specified group lost ambulation, compared with four in the placebo group.
Translarna also showed a benefit over placebo with regard to performance on timed function tests and the North Star Ambulatory Assessment test. Additionally, PTC Therapeutics said a pre-specified meta-analysis of the combined ACT DMD and Phase IIb trials showed a significant benefit of Translarna across the primary and key secondary endpoints. The company further noted that ACT DMD results confirmed a favourable safety profile for the drug, "which was generally well-tolerated, consistent with results from previous studies."
Prior to the release of ACT DMD data, Cowen & Co. analyst Ritu Baral suggested the trial had a "greater than 50-percent chance" of being successful, adding that she hoped patients would be able to walk 30 metres further on the drug, which she said was "the threshold of clinical meaningfulness." According to RBC Capital Markets analyst Simos Simeonidis, Translarna could potentially achieve annual sales of up to $900 million at its peak in the US and Europe, based on an estimated cost of $300 000 a year. PTC Therapeutics says nmDMD affects about 2000 boys in the US and 2500 in Europe. Chief financial officer Shane Kovacs remarked that even though the ACT DMD results suggest patients with "moderate disease" may be in the "optimal window" for therapy with Translarna, he did not expect regulators to limit the drug's use to those patients, since in addition to benefitting muscle tissue, he said it should also improve respiratory and cardiac function.
Meanwhile, Translarna is also in late-stage testing to treat cystic fibrosis, for which it recently submitted an EU application, and could generate an additional $1.3 billion in peak sales, Simeonidis said. The FDA and the European Commission have granted Translarna orphan drug status for Duchenne muscular dystrophy, cystic fibrosis, mucopolysaccharidosis I, and aniridia.
