The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) favors the renewal of the conditional marketing authorization of PTC Therapeutics’ Translarna (ataluren), an investigational drug in development for ambulatory patients 5 years and older, who have nonsense mutation Duchenne muscular dystrophy (nmDMD). Under this conditional marketing authorization renewal, EMA has requested PTC to conduct a long-term, post-authorization clinical trial. A decision from the European Commission should be issued within three months.
“We are pleased with this outcome which took into account all available data for Translarna,” Stuart W. Peltz, PhD, Chief Executive Officer, PTC Therapeutics, said in a press release. “This decision reflects the benefit that Translarna is having for patients suffering from nonsense mutation Duchenne muscular dystrophy.”
“The consistency of Translarna’s benefit shown across key endpoints is impressive for a dystrophin replacement therapy,” said Craig McDonald, MD, professor of Pediatrics and Chair of the Department of Physical Medicine & Rehabilitation at the University of California. “I am encouraged for the DMD community by the CHMP’s recommendation.”
PTC Therapeutics now will conduct an 18-month, randomized, placebo-controlled clinical trial with nmDMD patients. Results should be available by early 2021. This clinical trial, a specific post-authorization obligation requested by the CHMP, then will be followed by an 18-month, open-label extension period in which all patients will be treated with Translarna.
This new clinical trial is expected to have a size similar to the ACT DMD trial. PTC will have the protocol finalized, upon further meetings with EMA. Conditional marketing authorizations are subject to annual reassessment and renewal.
The ACT DMD study was the largest placebo-controlled investigation to ever focus on DMD patients. It was designed as a multi-center, randomized, double-blind Phase 3 trial (NCT01826487) that tested 228 patients in 53 study sites across 18 countries. Participants were 7 to 16 years old, and were grouped to receive either 40 mg per kilogram bodyweight of Translarna per day, or a placebo for a time of 48 weeks. Results reported in late 2015 showed the drug was able to induce significant therapeutic benefits as measured by a six-minute walk test, the North Star Ambulatory Assessment test, and several other timed function tests.
“For boys with Duchenne, every day matters and functional loss cannot be regained. Patients need access to innovative new therapies like Translarna,” said Filippo Buccella, founder of the Italian Parent Project, a patient advocacy group for Duchenne Muscular Dystrophy.
Translarna is an investigational new drug not yet approved by the Food and Drug Administration (FDA) for DMD, but has been granted orphan drug designation for DMD, cystic fibrosis, and mucopolysaccharidosis I (MPS1), which is caused by a deficiency in an essential enzyme responsible for the breakdown of byproducts in cells.
Translarna is a protein restoration drug that enables the formation of a new and functional protein in patients with genetic disorders like nmDMD that are caused by nonsense mutations – a modification in the genetic code that stops the synthesis of an essential protein. The resulting genetic disorder is determined by which protein cannot be fully expressed and is no longer functional, such as dystrophin, in DMD.