FDA Grants Breakthrough Therapy to Sickle Cell Treatment Crizanlizumab

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to the investigational drug crizanlizumab (SEG101) for the prevention of vaso-occlusive crises (VOCs) in patients with sickle cell disease.

Crizanlizumab, an anti-P-selectin monoclonal antibody, reduces VOCs by binding to P-selectin on platelets and endothelium in blood vessels, inhibiting interactions between cells. The FDA grants Breakthrough Therapy designation to treatments that are being developed to treat serious or life-threatening diseases or conditions and are substantially better than existing options.

"Painful sickle cell crises matter because they can disrupt patients' lives, and often require hospital visits and medical attention," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "We look forward to working closely with the FDA over the coming months toward making crizanlizumab, a therapy that has the potential to prevent sickle cell pain crises, available in the US as soon as possible."

Data from the phase 2 SUSTAIN trial of crizanlizumab supported the FDA’s decision to grant Breakthrough Therapy designation. Patients in sustain were treated with either crizanlizumab 2.5 mg/kg or 5 mg/kg, or placebo.

SUSTAIN showed that crizanlizumab reduced the median annual rate of vaso-occlusive crises leading to medical visits by 45.3% compared to placebo (1.63 vs 2.98, P = .010) in patients with sickle cell disease with or without hydroxyurea therapy.

Results from SUSTAIN also showed that crizanlizumab significantly increased the percentage of patients who did not experience any vaso-occlusive crises compared to placebo (35.8% vs 16.9%, P = .010).

The incidence of treatment-emergent adverse events was 86.4% for patients in the crizanlizumab treatment arm compared to 88.7% for patients in the placebo group, and serious adverse events occurred in 25.8% and 27.4% of patients, respectively. Patients receiving crizanlizumab experienced a low 3% incidence of discontinuations due to adverse events.

Adverse events that occurred in ≥10% of patients in either crizanlizumab treatment arm and at minimum double the frequency compared to placebo included arthralgia, diarrhea, pruritus, vomiting, and chest pain.

Novartis anticipates filing a New Drug Application for crizanlizumab in the first half of 2019.