- 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.
- 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 ….”
- 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.
- Unknown long-term efficacy.
- Some analyses are exploratory.