(TERMINATED) Study to determine the effect of SAR302503 on normal and malignant megakaryocytes

Somatic mutations in JAK2 and MPL are associated with BCR-ABL negative myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Since the identification of JAK2 mutations in MPNs, there has been an intense effort to develop JAK inhibitors as treatments for MPNs. Although one JAK2 inhibitor, ruxolitinib, has been approved for use in treating primary myelofibrosis, studies suggests that the drug alleviates symptoms associated with PMF, but does not reduce the JAK2 mutant allele burden. Moreover, ruxolitinib affects the development of normal hematopoietic cells. These observations provide the rationale for development of alternative inhibitors of the JAK/STAT pathway.