February 23, 2016
By Mark Terry, BioSpace.com Breaking News Staff
South Plainfield, N.J.-based PTC Therapeutics, Inc. announced today that the U.S. Food and Drug Administration (FDA) issued a Refuse to File letter about the company’s New Drug Application (NDA) for Translarna (ataluren) for Duchenne muscular dystrophy (DMD).
In the letter, the FDA apparently indicates that PTC’s application was “not sufficiently complete to permit a substantive review.”
Translarna is being evaluated as a treatment for nonsense mutation Duchenne muscular dystrophy (nmDMD). DMD is caused by a dysfunctional dystrophin protein, which results in progressive muscle wasting. More common in boys, patients usually lose the ability to walk by the age of 10 years and experience life-threatening lung and heart problems in their late teens and twenties. It affects about 1 in every 3,500 to 5,000 male children. Estimates are that nonsense mutations are responsible for about 13 percent of DMD cases, or about 2,000 patients in the U.S.
Translarna has been designated an orphan medicinal product by the European Medicines Agency (EMA) and given orphan drug designation by the FDA. It is the only Phase III-approved treatment for DMD in the world.
The drug has had a number of problems in clinical trials. In 2010 in a Phase IIb trial, it failed to meet its primary endpoints. Unexpectedly, the EMA reevaluated the drug and granted conditional approval based on “some evidence of effectiveness” and the fact that there was little if any alternative to the drug.
It has been a very bad year for companies focused on DMD therapeutics. In January, the FDA failed to approve San Rafel, Calif.-based BioMarin Pharmaceutical Inc. ’s application for Kyndrisa (drisapersen) for DMD. The FDA also turned down Cambridge, Mass.-based Sarepta Therapeutics ’s application for its DMD drug eteplirsen. Although eteplirsen had shown some positive results in a clinical trial, it was a tiny trial with only 12 patients. It appeared to have fewer side effects than BioMarin’s Kyndrisa.
On Jan. 26, Cambridge, Mass.-based Akashi Therapeutics announced that after one of its patients in a clinical trial for HT-100 in DMD developed serious, life-threatening health problems, it halted the trial. The company indicates it is working with the FDA to resolve the issue. The patient with the adverse affects was on the highest dose of the drug, and to date, no other patients in the lower-dose cohorts have had serious side effects.
PTC Therapeutics didn’t take the news well, although it has been on a fairly steady downturn for the last year. Shares traded on Mar. 17, 2015 for $77.53, dropped to $44.48 on July 8, then spiked briefly to $61.85 on July 20. Shares then fell to $25.11 on Sept. 29, rose briefly to $34.68 on Nov. 18, then dropped to $29.77 on Feb. 17, 2016. Shares are currently trading for $15.76.
