Translarna Preserved Walking 5-plus Years in DMD Boys

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by Steve Bryson PhD |

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Translarna (ataluren) treatment delayed the loss of walking abilities by more than five years in boys with Duchenne muscular dystrophy (DMD) who carry nonsense mutations in their DMD gene, according to a study based on real-world data.

The investigational therapy also slowed lung function decline by almost two years.

These most recent findings from the STRIDE registry — an ongoing, observational and international study — were presented at the World Muscle Society (WMS) 2021 Virtual Congress, being held Sept 20–24.

“The five-year analysis of the STRIDE registry clearly demonstrates Translarna’s profound impact on changing the course of disease progression. We are all proud to see Translana’s life-changing effect on boys with Duchenne,” Stuart Peltz, PhD, CEO of PTC Therapeutics, the therapy’s developer, said in a press release. “The results robustness showing both a five-year delay in loss of walking as well as its ability to prolong lung function confirms what we have seen in our clinical trials.”

The results “add to the totality of the evidence of Translarna’s benefit for the patients and their families,” he added.

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The STRIDE study (NCT02369731), conducted in partnership with the neuromuscular network TREAT-NMD, is following patients treated with Translarna, plus standard care (including corticosteroids), for at least five years.

The study’s primary goal is to assess the routine, real-world use of Translarna for people with a nonsense mutation in their DMD gene. This gene provides instructions to make dystrophin, one of a group of proteins that work together to strengthen muscle fibers and protect them from damage.

A nonsense mutation in the DMD gene prematurely stops dystrophin production, leading to a shorter, inactive protein, causing muscles to weaken over time. Translarna allows cells to ignore this mutation and generate functional dystrophin.

Data from 241 boys — enrolled in 13 countries for five years — were compared with DMD patients receiving standard treatment in the CINRG study (NCT00468832), designed to observe the natural course of the disease long term.

Analysis of five years of registry data revealed boys treated with Translarna plus standard care lost their walking abilities at the median age of 17.9 years, compared with 12.5 years for those on standard treatment alone — more than a five-year improvement.

By age 12, 80% of boys who received Translarna were still walking compared with 52% in CINRG.

A decline in lung function below 60% in boys treated with Translarna occurred at the median age of 17.6 years versus 15.8 years for those who did not receive the therapy — a 1.8-year difference. Below 60% in lung function is considered the benchmark to begin respiratory physical therapy, PTC said.

“Watching your child losing his abilities, until he can no longer walk or even breathe without help is heartbreaking,” said Filippo Buccella, patient advocate and founder of the MD association Parent Project Italy. “We are starting to see more evidence that Translarna can potentially give children many more years of freedom, and this will bring real hope to us parents.”

Translarna was well-tolerated, with adverse event data consistent with the known safety profile, representing more than 1,000 patient-years of exposure — a measure that takes into account treated patients and study duration.

Translarna is approved in Europe for DMD patients 2 and older who have  nonsense mutations and can walk. Expanding its use to those unable to walk has been recommended recently. In the U.S., however, the U.S Food and Drug Administration rejected PTC’s bid for Translarna’s approval, citing insufficient evidence supporting its effectiveness.

The company now is testing the long-term impact of Translarna on walking abilities in a Phase 3, placebo-controlled clinical trial (NCT03179631) in 250 boys, 5 and older, who can walk.