FDA News

FDA grants breakthrough therapy status to SEG101 for pain crises in sickle cell disease

The FDA granted breakthrough therapy designation to crizanlizumab for the prevention of vaso-occlusive crises among patients with sickle cell disease.

Vaso-occlusive crises are extremely painful and unpredictable events that occur among patients with all genotypes of sickle cell disease.

These crises — which can lead to chronic and acute complications, and also are associated with increased mortality — occur when blood cells stick to each other and to blood vessels, creating blockages.

Crizanlizumab (SEG101, Novartis) — a humanized anti-P-selectin monoclonal antibody administered via monthly infusion — binds to P-selectin on the surface of platelets and endothelium in the blood vessels.

The agent has been shown to inhibit interactions between red blood cells, sickled red blood cells, endothelial cells, platelets and leukocytes, preventing these cells from being able to bind to P-selectin, a key driver of the vaso-occlusive process.

“Painful sickle cell crises matter because they can disrupt patients’ lives, and often require hospital visits and medical attention,” Samit Hirawat, MD, head of Novartis Oncology Global Drug Development, said in a company-issued press release. “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 U.S. as soon as possible.”

Novartis officials expect to make a regulatory filing for crizanlizumab with the FDA in the first half of this year.

The FDA based breakthrough therapy designation for crizanlizumab based on positive results of the phase 2 SUSTAIN trial, designed to compare crizanlizumab with placebo among patients with sickle cell disease.

Crizanlizumab reduced the median annual rate of vaso-occlusive crises that led to health care visits by 45.3% compared with placebo (1.63 vs. 2.98; P = .01). Researchers observed the benefit among patients regardless of whether they received hydroxyurea therapy.

Results also showed crizanlizumab significantly increased the percentage of patients who did not experience any vaso-occlusive crises during treatment (35.8% vs. 16.9%; P = .01).

Investigators reported comparable incidence of treatment-emergent adverse events (86.4% vs. 88.7%) and serious adverse events (25.8% vs. 27.4%) in the crizanlizumab and placebo groups.

Three percent of patients who received crizanlizumab discontinued treatment due to adverse events.

Adverse events that occurred at least twice as often in the crizanlizumab group included arthralgia, diarrhea, pruritus, vomiting and chest pain. Researchers observed no increase in infections in the crizanlizumab group.

The FDA granted breakthrough therapy designation to crizanlizumab for the prevention of vaso-occlusive crises among patients with sickle cell disease.

Vaso-occlusive crises are extremely painful and unpredictable events that occur among patients with all genotypes of sickle cell disease.

These crises — which can lead to chronic and acute complications, and also are associated with increased mortality — occur when blood cells stick to each other and to blood vessels, creating blockages.

Crizanlizumab (SEG101, Novartis) — a humanized anti-P-selectin monoclonal antibody administered via monthly infusion — binds to P-selectin on the surface of platelets and endothelium in the blood vessels.

The agent has been shown to inhibit interactions between red blood cells, sickled red blood cells, endothelial cells, platelets and leukocytes, preventing these cells from being able to bind to P-selectin, a key driver of the vaso-occlusive process.

“Painful sickle cell crises matter because they can disrupt patients’ lives, and often require hospital visits and medical attention,” Samit Hirawat, MD, head of Novartis Oncology Global Drug Development, said in a company-issued press release. “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 U.S. as soon as possible.”

Novartis officials expect to make a regulatory filing for crizanlizumab with the FDA in the first half of this year.

The FDA based breakthrough therapy designation for crizanlizumab based on positive results of the phase 2 SUSTAIN trial, designed to compare crizanlizumab with placebo among patients with sickle cell disease.

Crizanlizumab reduced the median annual rate of vaso-occlusive crises that led to health care visits by 45.3% compared with placebo (1.63 vs. 2.98; P = .01). Researchers observed the benefit among patients regardless of whether they received hydroxyurea therapy.

Results also showed crizanlizumab significantly increased the percentage of patients who did not experience any vaso-occlusive crises during treatment (35.8% vs. 16.9%; P = .01).

Investigators reported comparable incidence of treatment-emergent adverse events (86.4% vs. 88.7%) and serious adverse events (25.8% vs. 27.4%) in the crizanlizumab and placebo groups.

Three percent of patients who received crizanlizumab discontinued treatment due to adverse events.

Adverse events that occurred at least twice as often in the crizanlizumab group included arthralgia, diarrhea, pruritus, vomiting and chest pain. Researchers observed no increase in infections in the crizanlizumab group.