Weekly SCD Practice Update

A pooled analysis of Phase 2 and Phase 3 clinical trials provides a detailed safety profile of crizanlizumab 5.0 mg/kg in sickle cell disease (SCD), showing predominantly mild to moderate adverse events alongside infrequent but notable serious infections and bleeding events.

Key Findings

  • Purpose
    To evaluate the safety of crizanlizumab 5.0 mg/kg by pooling adverse-event data across multiple clinical trials in individuals with SCD.
  • Population
    Safety data were pooled from four studies: SUSTAIN (Phase 2), SOLACE-adults, SOLACE-kids, and STAND (Phase 3), including both crizanlizumab-treated and placebo-treated participants across pediatric and adult cohorts.
  • Headline Result
    • The most common adverse events among crizanlizumab-treated participants included headache, pyrexia, and infections.
    • Most adverse events were mild to moderate in severity, though grade 3 infections and bleeding events were observed, and a small number of grade 5 infection-related events occurred.
    • Overall rates of serious adverse events were low and were similar or modestly higher compared with placebo, depending on the event category.
    • Treatment discontinuation due to adverse events remained uncommon.
  • Why It Matters
    Crizanlizumab targets P-selectin–mediated adhesion to reduce vaso-occlusive events in SCD. A clear understanding of its safety profile—including uncommon but serious infections and bleeding—is essential for informed risk–benefit discussions, monitoring strategies, and shared decision-making in clinical practice.
  • Evidence Gaps & Limitations
    This pooled analysis focuses on safety rather than efficacy and combines trials with differing designs, durations, and populations, introducing heterogeneity. Long-term safety beyond trial follow-up and safety in broader real-world populations were not assessed.

Source: Journal of Sickle Cell Disease“Safety profile of crizanlizumab 5.0 mg/kg in sickle cell disease: pooled data from clinical trials.”

Regulatory & Guideline Watch

Crizanlizumab 5.0 mg/kg is approved in the United States to reduce the frequency of vaso-occlusive crises in adults and pediatric patients aged 16 years and older with SCD. Current guidance and expert opinion support individualized therapy selection and routine safety monitoring when crizanlizumab is used.

The European Medicines Agency (EMA) previously granted conditional approval, which was later revoked after the STAND trial did not confirm clinical efficacy. Current guidelines emphasize individualized therapy selection and continued safety monitoring when crizanlizumab is used.