Novartis has secured priority review status from the US Food and Drug Administration (FDA) for its humanized anti-P-selectin monoclonal antibody crizanlizumab (SEG101) for the prevention of vaso-occlusive crises (VOCs) in patients with sickle cell disease (SCD).
In January 2018, the company announced that crizanlizumab was granted breakthrough therapy designation by the FDA.
Novartis’ application for the investigational drug is backed by results from a phase 2 trial, called SUSTAIN. In this mid-stage trial, the monoclonal antibody at 5mg/kg was shown to have lowered the median annual rate of VOCs leading to health care visits by 45.3%, in comparison to placebo in patients with or without hydroxyurea.
Furthermore, clinically significant reductions were observed in the crizanlizumab arm in the frequency of VOCs among patients irrespective of sickle cell disease genotype or hydroxyurea use in the SUSTAIN trial.
VOCs, which are also called sickle cell pain crises, are known to be unpredictable and extremely painful events that can result in serious life-threatening complications and even death.
Novartis global drug development head and chief medical officer John Tsai said: “The FDA’s decision to give crizanlizumab priority review reflects the impact that this medicine could have for the many thousands of US sickle cell adult patients who experience painful vaso-occlusive crises.
“We are looking forward to the opportunity, if crizanlizumab is approved, to reimagine medicine in sickle cell disease for patients who live with this condition every day of their lives.”
Crizanlizumab has been designed to bind to the P-selectin molecule, which is found on the surface of platelets and endothelium in the blood vessels. The drug has been shown to block interactions between endothelial cells, red blood cells, platelets, sickled red blood cells, and leukocytes, thereby preventing the cells from binding with P-selectin.
P-selectin is considered to be of the key drivers of the vaso-occlusive process.
The priority review designation for crizanlizumab will reduce the FDA review period for the drug from the standard ten months to six months.
The SUSTAIN trial of the investigational drug is part of the SENTRY clinical programme, which comprises multiple mid-stage and late-stage trials such as SOLACE-adults (A2202) phase 2 study, SOLACE-kids (B2201) phase 2 study, STAND (A2301) Phase III study and the SUCCESSOR retrospective cohort study.