The New England Journal of MedicineOral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks

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A phase 3 clinical trial evaluated the efficacy of oral sebetralstat for on-demand treatment of hereditary angioedema (HAE) attacks, addressing the limitations of current parenteral therapies. The study compared two doses of sebetralstat against placebo in a randomized, double-blind, three-way crossover design.

Study Design:

• Phase 3, double-blind, three-way crossover trial
• 136 participants aged ≥12 years with type 1 or 2 HAE
• Randomized to receive up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack
• 110 participants treated a total of 264 attacks

Key Findings:

• Median time to beginning of symptom relief:
  • 300 mg sebetralstat: 1.61 hours
  • 600 mg sebetralstat: 1.79 hours
  • Placebo: 6.72 hours
• Faster time to reduction in attack severity with both sebetralstat doses vs. placebo (p=0.004 for 300 mg, p=0.003 for 600 mg)
• Faster time to complete resolution with both sebetralstat doses vs. placebo (p=0.002 for 300 mg, p<0.001 for 600 mg)
• Percentage of attacks with complete resolution within 24 hours:
  • 300 mg sebetralstat: 42.5%
  • 600 mg sebetralstat: 49.5%
  • Placebo: 27.4%
• Similar safety profiles between sebetralstat and placebo
• No serious adverse events related to the trial agents reported

HCN Medical Memo
The introduction of an effective oral medication for HAE attacks could significantly improve patient care by reducing treatment delays and increasing adherence. Physicians should stay informed about the potential availability of sebetralstat and consider its future role in HAE management strategies.

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