english.prescrire.org > Spotlight > Archives : 2018 > Ataluren (Translarna°) and Duchenne muscular dystrophy. No proof of efficacy and poorly documented harms

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Ataluren (Translarna°) and Duchenne muscular dystrophy. No proof of efficacy and poorly documented harms

FEATURED REVIEW Duchenne muscular dystrophy is a fatal, severely disabling disease that profoundly affects the lives of patients and their carers. But even in this very serious situation, there is no justification for proposing a drug with no proven efficacy beyond a placebo effect, and with poorly documented adverse effects.
Full review (4 pages) available for download by subscribers.

Abstract

  • Duchenne muscular dystrophy is a serious genetic disorder that almost exclusively affects boys. It is caused by a mutation in the gene encoding dystrophin, a protein that is important for muscle structure and contraction. Clinically, the disease presents as muscle weakness at 2 to 3 years of age, progressing to difficulty walking. Affected patients generally lose the ability to walk by the age of 13 years. They also develop cardiomyopathy and respiratory insufficiency, usually resulting in death by the age of 30.
     
  • Therapy for Duchenne muscular dystrophy is mainly based on preventing and treating its complications, primarily through physiotherapy, orthoses and respiratory support. Among the drugs proposed, corticosteroids probably delay loss of ambulation, but their prolonged use is limited by adverse effects.
     
  • Ataluren, a gene readthrough inducing agent, has been authorised for the treatment of Duchenne muscular dystrophy resulting from a nonsense mutation of the dystrophin gene, in patients who are aged 5 years or older and still able to walk. Clinical evaluation is based on two randomised placebo-controlled trials in a total of 402 boys aged 5 years and older. The trial endpoints did not include the frequency of major complications. After 48 weeks of treatment, no statistically significant difference was demonstrated between ataluren and placebo in the mean distance walked in 6 minutes (the primary endpoint).
     
  • Ataluren can provoke hypertension and hyperlipaemia, the long-term consequences of which are unknown. The other documented adverse effects of ataluren are mainly gastrointestinal in nature. Ataluren may increase the incidence of falls and fractures, risks to which the patients are already exposed as a result of the disease.
     
  • Ataluren appears to increase the renal toxicity of certain antibiotics. It inhibits the activity of various organic anion transporters (OAT1, OAT3 and OATP1B3), making interactions likely with substrates of these transporters. 
  •  NOT ACCEPTABLE  In two clinical trials including about 400 patients, ataluren was not significantly more effective than placebo in reducing disability. It can provoke hypertension and hyperlipaemia, with unknown long-term consequences, gastrointestinal adverse effects, and possibly falls and fractures. Duchenne muscular dystrophy is a fatal, severely disabling disease that profoundly affects the lives of patients and their carers. But even in this very serious situation, there is no justification for proposing a drug with no proven efficacy beyond a placebo effect, and with poorly documented adverse effects. As of mid-2017, the harm-benefit balance of ataluren is unfavourable: it should only be used in the clinical trial setting.

©Prescrire 1 January 2018

"Ataluren (Translarna°) and Duchenne muscular dystrophy. No proof of efficacy and poorly documented harms" Prescrire Int 2018; 27 (189): 5-8. (Pdf, subscribers only)
Download the full review.
Pdf, subscribers only
 
Prescrire's rating:
Prescrire's rating
 NOT ACCEPTABLE