Beta-thalassemias and hemoglobinopathies are serious inherited blood diseases caused by
abnormal or deficiency of beta A chains of hemoglobin, the protein in red blood cells which
delivers oxygen throughout the body.The diseases are characterized by hemolytic anemia, organ
damage, and early mortality without treatment. Increases in another type of (normal)
hemoglobin, fetal globin (HbF), which is normally silenced in infancy, reduces anemia and
morbidity. Even incremental augmentation of fetal globin is established to reduce red blood
cell pathology, anemia, certain complications, and to improve survival.
This trial will evaluate an oral drug discovered in a high throughput screen, which increases
fetal globin protein (HbF and red blood cells expressing HbF)and messenger ribonucleic acid
(mRNA) to high levels in anemic nonhuman primates and in transgenic mice. The study drug acts
by suppressing 4 repressors of the fetal globin gene promoter in progenitor cells from
patients. The drug has been used for 50 years in a combination product for different actions
- to enhance half-life and reduce side effects of a different active drug- and is considered
safe for long-term use.
This trial will first evaluate 3 dose levels in small cohorts of nontransfused patients with
beta thalassemia intermedia. The most active dose will then be evaluated in larger subject
groups with beta thalassemia and other hemoglobinopathies, such as sickle cell disease.