Ataluren

Translarna has a checkered past with the FDA and, despite scoring a thumbs-up in Europe back in 2014, recently met a major marketing setback there, as well. With the writing apparently on the wall, PTC Therapeutics has called off its latest bid for FDA approval of its Duchenne muscular dystrophy (DMD) drug Translarna. Late Thursday, PTC revealed that it withdrew its FDA application for Translarna in nonsense mutation DMD after receiving feedback on its filing from the regulator. "FDA shared that based on its review to date, the data in the [New Drug Application] submission are unlikely to meet the Agency's threshold of substantial evidence of effectiveness to support approval of Translarna," Matthew Klein, M.D., PTC's chief executive, explained in a statement. PTC is "disappointed that FDA approval cannot be achieved," Klein said, citing the decades of development work that have gone into the company's protein restoration therapy. In a letter to the U.S. DMD community, PTC cited unresolvable "differences in data interpretation" with the FDA, Pharmaphorum reports.  Translarna has a checkered past with the FDA and, despite scoring a thumbs-up in Europe back in 2014, recently met a major marketing setback there, as well.Stateside, the FDA initially declined to review PTC's Translarna application in 2016, telling the company its application was incomplete. About a year and a half later, the FDA formally rejected the drug, citing the need for PTC to run an additional trial "at a minimum" to better validate Translarna's effectiveness. The FDA also flagged other "nonclinical and [chemistry, manufacturing and controls] matters" in the approval bid.PTC announced it would make another attempt at U.S. approval in early 2024, pointing to "recent feedback" from the FDA. Now, that effort is ending without success.The drug has also suffered recent regulatory setbacks in the EU and, despite some pushback from European officials, the European Medicines Agency's human medicines committee ultimately decided not to renew the drug's conditional marketing authorization in late 2024. The European Commission, which has final say on approvals in the bloc, made the same call last March. European regulators blessed the med with a conditional nod in 2014 on results from a phase 2b study that favored Translarna over placebo on a six-minute walk test after 48 weeks of treatment. But that study and a subsequent trial did not produce statistically significant results on the metric.Back in the U.S., PTC also faced FDA friction around its Friedreich's ataxia candidate vatiquinone last year when the regulator denied approval of the candidate over a lack of "substantial evidence of efficacy" in the company's filing.  Translarna, which goes by the generic moniker ataluren, is a protein restoration therapy that is designed to allow the formation of a functioning protein in patients with genetic disorders caused by nonsense mutations. PTC describes that type of mutation as an alteration in the genetic code that prematurely halts the synthesis of an essential protein. In the case of DMD, that protein would be dystrophin.