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Clinical Trial Led by UTHSC’s Kenneth Ataga, MD, Results in FDA Approval of New Sickle Cell Treatment

Dr. Kenneth Ataga

Patients with sickle cell disease will soon have a new treatment option to reduce pain crises caused by obstructed blood flow. The FDA has approved use of the drug crizanlizumab based on the results of a clinical trial led by Kenneth Ataga, MD, Plough Foundation Endowed Chair in Sickle Cell Disease and director of the Center for Sickle Cell Disease at the University of Tennessee Health Science Center.

Dr. Ataga, who is also the director of the Memphis Consortium for Sickle Cell Disease and Non-Malignant Hematology Research, was the lead principal investigator of the multicenter, Phase II SUSTAIN trial. Part of a larger program of studies, the SUSTAIN trial was designed to test the safety and efficacy of crizanlizumab in reducing the frequency of vaso-occlusive crises (VOCs), or pain crises, in adult and pediatric patients ages 16 years and older with sickle cell disease. The study participants were recruited from 60 sites in the United States, Brazil and Jamaica.

Sickle cell disease is an inherited blood disorder in which the red blood cells are abnormally shaped (in a crescent or “sickle” shape), which restricts the flow of blood and limits oxygen delivery to the body’s tissues, leading to severe pain and organ damage. According to the Centers for Disease Control and Prevention, sickle cell disease affects approximately 100,000 Americans.

Considered the clinical hallmark of the disease, sickle cell pain crises are unpredictable, severe events associated with life-threatening complications. They are triggered, in part, by multicellular interactions that form clusters of cells, which can block or reduce the blood flow to organs. Sickle cell pain crises are the main reason why individuals living with sickle cell disease go to the emergency room and are admitted to the hospital.

Phase II SUSTAIN was a 52-week randomized, placebo-controlled trial conducted as a double-blind study. A total of 198 patients with any genotype of sickle cell disease received either a 5mg/kg body weight or 2.5mg/kg body weight dose of crizanlizumab or a placebo. Results showed that the higher dose significantly lowered the median annual rate of VOCs by 45 percent (1.63 vs 2.98 compared to placebo). Reductions in the frequency of VOCs were observed among patients regardless of sickle cell disease genotype and/or use of hydroxyurea, the only other FDA-approved treatment proven to reduce the frequency of painful episodes at the time of the trial. Results also showed that treatment with crizanlizumab increased the percentage of patients who did not experience any vaso-occlusive crises compared to the placebo.

Dr. Ataga presented these findings at the 2016 American Society of Hematology annual meeting in San Diego, and the results were published in The New England Journal of Medicine in early 2017. Based on this data, the FDA granted crizanlizumab Priority Review, which shortened FDA review time from the standard 10 months to six.

Crizanlizumab is only the third FDA-approved drug to treat sickle cell disease. “Despite our understanding of the pathophysiology of sickle cell disease, development of therapies has lagged,” Dr. Ataga said. “It is exciting to have approval for a new treatment for people living with this very difficult condition.”