Combination drug therapy for ALS is promising

  • Paganoni S & al.
  • N Engl J Med
  • 3 Sep 2020

  • curated by Susan London
  • Clinical Essentials
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Takeaway

  • Patients with amyotrophic lateral sclerosis (ALS) had slower functional decline when given the combination of sodium phenylbutyrate and taurursodiol as compared with placebo.

Why this matters

  • Safe, effective treatments for ALS are lacking.
  • Editorial says data are "tantalizing" and calls for confirmation in a phase 3 trial, noting that broader eligibility criteria would offer value while still including a subgroup analysis of patients who met the phase 2 eligibility criteria.

Key results

  • Sodium phenylbutyrate-taurursodiol vs placebo on ALS Functional Rating Scale-Revised (ALSFRS-R) score:
    • Mean rate of change: −1.24 vs −1.66 points/month.
    • Difference: 0.42 points/month (P=.03).
  • Groups not significantly different for:
    • Rates of decline in:
      • Isometric muscle strength,
      • Plasma phosphorylated axonal neurofilament H subunit level, or
      • Slow vital capacity.
    • Time to death, tracheostomy, or permanent ventilation.
    • Time to death, tracheostomy, permanent ventilation, or hospitalization.
  • Sodium phenylbutyrate-taurursodiol group had higher rates of:
    • Gastrointestinal disorders (67% vs 60%),
    • Respiratory, thoracic, mediastinal disorders (33% vs 21%),
    • Cardiac disorders (8% vs 0%), and
    • Eye disorders (6% vs 2%).

Study design

  • US phase 2, multicenter, randomized controlled trial among 137 patients with definite ALS, symptom onset within previous 18 months (CENTAUR trial).
  • Participants were randomly assigned 2:1 to double-blind sodium phenylbutyrate-taurursodiol vs placebo, orally/through feeding tube, once daily for 3 weeks then twice daily.
  • Main outcome: rate of decline in ALSFRS-R score through 24 weeks.
  • Funding: Amylyx Pharmaceuticals; others.

Limitations

  • Patients had well-established disease.
  • Smaller sample, shorter trial duration.
  • Shortcomings of ALSFRS-R.