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FDA Grants Novartis Priority Review for Sickle Cell Therapy

July 17, 2019

Novartis said the U.S. Food and Drug Administration has granted Priority Review for its experimental sickle cell medicine crizanlizumab for the prevention of vaso-occlusive crises in patients with sickle cell disease.

Priority Review is granted to therapies the FDA determines have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The designation is intended to shorten the FDA review period to six months from the standard ten months. Novartis was granted Breakthrough Therapy designation for crizanlizumab in December 2018.

If approved, crizanlizumab is expected to represent the first monoclonal antibody targeting the P-selectin mediated multi-cellular adhesion in sickle cell disease.

The filing comes as the competition to bring new sickle cell therapies to market is heating up. Global Blood Therapeutics has a once-daily candidate voxelator that showed it could reduce the destruction of red blood cells in late stage trials. Bluebird Bio’s gene therapy Zynteglo for transfusion-dependent beta thalassemia was just approved and the company has data showing it can eliminate VOCs in some patients with sickle cell anemia. Other companies are developing sickle cell therapies using gene-editing technologies, including CRISPR Therapeutics and Vertex Pharmaceuticals.

Vaso-occlusive crises (VOCs) are unpredictable and painful events that can lead to serious acute and chronic life-threatening complications and death. They are the most common cause of emergency room visits and hospital admissions for SCD patients, with total medical costs exceeding $1.1 billion annually in the United States. Novartis projects sales of more than $1 billion for crizanlizumab if it is approved.

Crizanlizumab is an investigational humanized monoclonal antibody that binds to a molecule called P-selectin on the surface of platelets and endothelium in the blood vessels, and has been shown to inhibit interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes. P-selectin is one of the major drivers of the vaso-occlusive process.

“The FDA’s decision to give crizanlizumab priority review reflects the impact that this medicine could have for the many thousands of U.S. sickle cell adult patients who experience painful vaso-occlusive crises,” said John Tsai, head of global drug development and chief medical officer, Novartis. “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.” 

The FDA submission is supported by phase 2 results from the SUSTAIN study, which showed that crizanlizumab reduced the median annual rate of VOCs that lead to health care visits, by 45.3 percent compared with placebo in patients with or without hydroxyurea (the current standard treatment). Clinically significant reductions in the frequency of VOCs were observed among patients regardless of sickle cell disease genotype or hydroxyurea use.

The study also demonstrated that a once-monthly infusion of crizanlizumab resulted in a doubling of patients who did not experience any VOCs versus placebo (36 percent versus 17 percent), a three-fold longer median time to first VOC versus placebo, and a 42 percent reduction in the median annual rate of days hospitalized versus placebo.

Sickle cell disease (SCD) is a debilitating inherited genetic blood disorder that affects the shape of the red blood cells and can make blood cells and blood vessels stickier than normal. When blood cells stick to one another, they can form multicellular adhesion clusters in the bloodstream. These clusters can reduce and block the flow of blood and oxygen, which can cause damage to the blood vessels and lead to acute and chronic complications, including painful VOCs, which are considered the clinical hallmark of the disease and the main reason why patients seek medical care. The average sickle cell patient in the United States is estimated to face nearly $1 million in total lifetime health care costs, according to Novartis. The company estimates that there are about 100,000 people with the disease in the United States and that about 60 percent of them experience two or more VOCs a year.

Photo: John Tsai, head of global drug development and chief medical officer, Novartis

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