Translarna Preserves Lung Function, Muscle Strength in DMD Boys, Real-World Data Show

Treatment with Translarna (ataluren) preserves lung function and muscle strength in boys with Duchenne muscular dystrophy (DMD), real-world data show.

The most recent results from the ongoing STRIDE registry — an observational study across more than 50 care centers in Europe and Israel — were presented at the 24th International Annual Congress of the World Muscle Society, held recently in Copenhagen, Denmark. The data was included in a poster titled “Pulmonary function in patients with Duchenne muscular dystrophy from the STRIDE registry and the CINRG natural history study: a matched cohort analysis.”

The STRIDE (NCT02369731) study resulted from a partnership between the TREAT-NMD neuromuscular network and Translarna’s developer, PTC Therapeutics. Conducted at approximately 56 sites across Europe and Israel, it follows patients for at least five years or until withdrawal.

The study aims to assess, in routine clinical practice, the long-term use of Translarna plus standard of care therapy in people with DMD caused by a nonsense mutation in the DMD gene — the specific indication that Translarna was designed to treat. A nonsense mutation refers to the introduction of a premature stop signal in the gene sequence, which ultimately leads to a shorter and dysfunctional dystrophin protein.

Researchers evaluated changes in neuromuscular, cardiac, and pulmonary function in a total of 187 DMD boys, who had experienced their first symptoms at a mean age of 2.7 years. These boys were compared with 187 matched DMD patients who participated in the ongoing CINRG study (NCT00468832). That study, by the Cooperative International Neuromuscular Research Group (CINRG), is the largest observational, longitudinal study assessing the natural course of the disease.

In both study groups, most participants received treatment with corticosteroids for one year or more — 56.7% in STRIDE and 55.1% in CINRG. Similar proportions took PTC’s Enflaza (deflazacort) — 24.6% in STRIDE and 23.5% in CINRG — or other corticosteroids (34.8% in each study).

Among DMD boys who were treated with Translarna for a mean total exposure of 633 days, only 2.1% had a predicted forced vital capacity (FVC) — an assessment of lung function — lower than 50%, the study results showed. That compared with 32.5% of CINRG participants, who did not received treatment with this therapy, according to the data.

This marked difference in lung function also was noted in FVC volume, or the amount of air in the lungs that can be exhaled following a deep breath, which was below one liter in 24.3% of the CINRG group. In contrast, none of the STRIDE participants showed such poor results.

“It’s very encouraging to see positive lung function results in a real world setting and provides reassurance that ataluren [Translarna] is slowing disease progression,” Eugenio Mercuri, MD, PhD, professor at Catholic University in Rome, and co-author of the study, said in a press release. “Respiratory failure is the primary cause of disability and death in patients with Duchenne and monitoring and preserving lung function is a key clinical priority.”

Clinical data also showed that treatment with Translarna could significantly preserve patients’ ability to stand up from lying and to climb stairs compared with natural disease course, according to the company.

The median age at which patients on Translarna lost the ability to stand up from lying in under 5 seconds was 12 years, which was three years later than what has been reported in untreated children (9.1 years).

“Across ambulation, physical function and lung function, the STRIDE data demonstrate that patients receiving Translarna preserved function for years longer than patients receiving standard of care,” added Stuart Peltz, PhD, CEO at PTC. “These are real world results that provide clinicians and regulators the true picture of patient response to treatment.”

Translarna is approved in the European Union, Iceland, Liechtenstein, Norway, Israel, and South Korea for the treatment of DMD in ambulatory patients ages 5 and older.

STRIDE is being performed as a post-approval safety study, per the European Medicines Agency (EMA), to gather data on Translarna’s safety, effectiveness, and prescription patterns in routine clinical practice.