- PTC Therapeutics appears to have hit another hurdle in its quest to prove its Duchenne muscular dystrophy drug Translarna, reporting Thursday the treatment didn't significantly increase the amount of a key muscle building protein in a group of 18 boys.
- The Food and Drug Administration has already rejected Translarna three times, but had agreed to consider new results under "accelerated review" procedures, leading to the data the biotech presented on Thursday. In spite of the miss, the company intends to discuss "potential approval pathways" for Translarna in the U.S. based on other data from the trial as well as earlier research.
- If that plan doesn't work, the company would need to wait until a bigger, placebo-controlled trial that can generate data, which is not expected to happen until the second half of 2022. Translarna is only approved for use the European Union.
Patients with Duchenne muscular dystrophy have limited treatment options. Sarepta's Exondys 51 and Vyondys 53 have been shown to spur production of small amounts of the muscle-building protein dystrophin in boys with specific mutations, while PTC's own Emflaza, a steroid, can increase muscle strength.
The promise of Translarna is its potential to boost dystrophin in a larger group of patients, those with so-called nonsense mutations. However, the FDA hasn't been persuaded. The agency refused to review it on two occasions and agreed a third time only after PTC invoked a rarely used rule allowing it to protest a refusal — an effort that resulted in an outright rejection and a request for more clinical data.
Following that setback, PTC and the FDA agreed that if the company could show, using new analytical methods, that dystrophin production significantly increased in patients treated with Translarna, the results would be sufficient for review under accelerated approval. The company would then have to confirm those findings in a larger, placebo-controlled trial.
PTC, however, hasn't succeeded in the first part of that plan. In the 18 patients who completed the study, dystrophin production increased 9%, but not at a level that researchers considered statistically significant. PTC also didn't specify how much dystrophin subjects produced at the start of the trial, making any benefit difficult to gauge.
Nonetheless, the company plans to go back to the FDA.
"We'll plan to discuss to discuss the dystrophin results, and the totality of the existing clinical and real-world data with the FDA to determine that there's a potential accelerated path to approval," CEO Stuart Peltz said in a call with Wall Street analysts.
Analysts were less optimistic. "We are cautious on the regulatory pathway forward given the primary miss here, and given the transition of the FDA commissioner, we are unclear how flexible the FDA could be," Cantor Fitzgerald analyst Alethia Young wrote in a note. RBC Capital Markets analyst Brian Abrahams added that the numbers seen weren't close to the bar the company believed the FDA has set.
Abrahams, instead, deemed the results "more likely to be a component" of a future U.S. approval filing, should the placebo-controlled study produce positive results next year.
Data from a trial of a Phase 1 Huntington's disease drug, due in the first half of this year, could be a more significant event for PTC, Young wrote, than another possible FDA review of Translarna.