Transthyretin amyloidosis: 2 oligonucleotide drugs found efficacious

  • Adams D & al.
  • N Engl J Med
  • 5 Jul 2018

  • curated by Susan London
  • Clinical Essentials
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Takeaway

  • Patisiran and inotersen may slow, even reverse, peripheral neuropathy in patients with transthyretin amyloidosis.

Why this matters

  • Transthyretin amyloidosis is a progressive, fatal disease with limited therapeutic options.

Key results

  • 18-month least-squares mean change in Neuropathy Impairment Score+7 score was more favorable with patisiran vs placebo (–6.0 vs 28.0; difference, –34.0 points; P<.001>
  • Better change was observed with patisiran in Norfolk Quality of Life-Diabetic Neuropathy score (difference in least-squares mean change, –21.1 points; P<.001 gait speed meter p and modified bmi>
  • Rate of mild/moderate infusion-related reactions was higher with patisiran (20% vs 10%); overall rates and types of adverse events were similar.
  • In similar trial among 172 patients (NEURO-TTR), weekly subcutaneous inotersen was superior to placebo at week 66 on Neuropathy Impairment Score+7 score (difference in least-squares mean change, –19.7 points; P<.001 and quality of life-diabetic neuropathy score points p there were higher rates death vs serious glomerulonephritis thrombocytopenia>
  • Editorialist : “the trials … represent a landmark ….”

Study design

  • Phase 3 trial among 225 patients with hereditary transthyretin amyloidosis having polyneuropathy randomly assigned 2:1 to intravenous patisiran or placebo every 3 weeks (APOLLO trial).
  • Main outcome: modified Neuropathy Impairment Score+7.
  • Funding: Alnylam Pharmaceuticals.

Limitations

  • Unknown long-term efficacy.
  • Some analyses are exploratory.

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