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our programs
Sickle Cell Disease
Etavopivat
Sickle cell disease is an inherited genetic disease that affects hemoglobin, the iron-containing protein in red blood cells (RBCs) responsible for transporting oxygen in the blood. People who have sickle cell disease inherit two abnormal hemoglobin genes, one from each parent.1
Mutated hemoglobin (HbS) clumps together in low-oxygen conditions to form long polymers that deform RBCs, resulting in sickle-like shapes. Sickle cells are stiff and have damaged membranes, causing the RBCs to clump and lyse in small blood vessels, which leads to anemia, inflammation, vaso-occlusive crises and increased risk of stroke. People with sickle cell disease report they experience more debilitatingly painful days than pain-free days.2
Repeated deformation also depletes ATP, the molecule that supplies energy for vital processes in RBCs. ATP is essential for maintaining RBC function. It enables the repair of damaged membranes and proper function of pumps and channels that maintain water and ion balance across the membrane.3,4,5
Sickle cell disease affects more than 20 million individuals globally according to the National Institutes of Health, including approximately 100,000 people in the United States.6 From 2010 to 2050, the annual number of newborns with sickle cell disease is expected to rise globally by about one-third.7 Sickle cell disease is most common in people with sub-Saharan African ancestry. In the United States, the majority of those affected by sickle cell disease are Black and Latino. It’s estimated that sickle cell disease occurs in one in every 365 Black Americans.8
Many people living with sickle cell disease often call themselves “warriors”—and rightfully so. Understanding their perspectives, their battles, as well as those of their loved ones, is critical to the work we do.
Despite recent advances, a blood and bone marrow transplant is the only current cure for sickle cell disease.1 We’re currently evaluating whether once-daily etavopivat could impact hemoglobin levels and the number of vaso-occlusive crises.
100 k
people with sickle cell disease in the U.S.
25-30 yrs
reduction in life expectancy**
55 %
days with pain*
A novel and multi-modal investigational approach.
A naturally produced metabolic enzyme in the body called pyruvate kinase-R (PKR) is thought to play a critical role as a regulator of the metabolic cycle through which oxygen is bound and released from hemoglobin.
Etavopivat is designed to activate PKR and thereby modulate RBC metabolism by impacting two critical pathways in RBCs. Our clinical studies of etavopivat will investigate whether decreasing 2,3-DPG may help oxygen bind to hemoglobin (i.e. increasing oxygen affinity), and thereby increase ATP and impact RBC function.
Development Status
We’re currently enrolling adults and adolescents with sickle cell disease into the Hibiscus Study, a registrational Phase 2/3 randomized, placebo-controlled, double-blind, multicenter trial to further evaluate the safety and efficacy of etavopivat. The FDA has granted etavopivat Fast Track, Rare Pediatric Disease and Orphan Drug designations. For more information, visit ClinicalTrials.gov/NCT04624659 or www.HibiscusStudy.com. The blinded, randomized, placebo-controlled portion of the ongoing Phase 1 study is complete. People with SCD are directly enrolling into the 12-week open label cohort receiving 400 mg of etavopivat daily.