Phase II study of SB1518, an orally available novel JAK2 inhibitor, in patients with myelofibrosis.

  title={Phase II study of SB1518, an orally available novel JAK2 inhibitor, in patients with myelofibrosis.},
  author={H. Joachim Deeg and O. Odenike and Bart L. Scott and Zeev E Estrov and Jorge E. Cortes and Deborah A. Thomas and H Zhu and Hagop M. Kantarjian and Srdan Verstovsek},
  journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
  volume={29 15\_suppl},
  • H. Deeg, O. Odenike, S. Verstovsek
  • Published 20 May 2011
  • Medicine
  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology
6515 Background: The JAK2V617F mutant enzyme has been linked to the pathogenesis of myeloproliferative neoplasms. SB1518 is a potent inhibitor of JAK2 and its JAK2V617F mutant. In Phase 1 study, myelofibrosis (MF) patients treated with SB1518 achieved steady-state plasma levels above the IC50 for JAK2 at all doses (100-600 mg/d). Target inhibition, measured by phosphorylation of STAT3, STAT5, and JAK proteins in PBMCs and whole blood, was also shown at all doses. 400 mg/d was chosen for Phase 2… 
A Critical Review of the Role and Limitations of JAK Inhibitors in Myelofibrosis Therapy
The discovery of JAK2V617F has rejuvenated interest in JAK-STAT, both as an oncogenic pathway and a drug target in BCR-ABL1-negative myeloproliferative neoplasms (MPN). While the majority of MPN
Therapy with JAK 1/2 inhibitors for myelofibrosis
There is emerging evidence that supports the use of JAK-inhibitors for MF in clinical practice, especially for patients with splenomegaly and constitutional symptoms, Nevertheless, possible side effects such as anemia and thrombopenia must be considered when prescribing these substances.
A closer look at pacritinib: a JAK2/FLT3 inhibitor for the treatment of myelofibrosis
Pacritinib, SB1518, a dual JAK2 and FMS-like tyrosine kinase 3 inhibitor has been suggested to provide clinical benefit to patients with MF without producing adverse hematologic events that restrict ruxolitinib utility.
JAK2 inhibitors and their impact in myeloproliferative neoplasms
Treatment guidelines addressing optimal stages for drug implementation, ideal dosing parameters and criteria for medication continuation/withdrawal may effectively resolve ongoing concerns and provide advancements in the morbidity and mortality of these multifaceted disease processes.
Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia.
Pacritinib, a dual JAK2 and FLT3 inhibitor which also inhibits IRAK1, has demonstrated the ability to favorably impact MF-associated splenomegaly and symptom burden, while having limited myelosuppression with manageable gastrointestinal toxicity.
JAK2 Inhibition: Current Roles in Myelofibrosis and Initial Lessons Learned from Mexico
As the future of MPN treatments is surveyed, it is clear that integration of scientific advancements must parallel timesensitive patient application so as to offer the greatest relief to those afflicted by the MPN disease burden.
Clinical potential of pacritinib in the treatment of myelofibrosis
Pacritinib, a JAK2 and FMS-like tyrosine kinase 3 (FLT3) inhibitor, has shown promising results in early phase trials with limited myelotoxicity and clinical responses that are comparable with those seen with ruxolitinib in MF, even in patients with severe thrombocytopenia.
Current Outlook on Molecular Pathogenesis and Treatment of Myeloproliferative Neoplasms
While JAK2 inhibitors appear to be promising in PV and ET, they need to be compared with standard therapies, such as hydroxyurea or interferon-based therapies, and future clinical development will focus on optimal combination partners and agents that target alternative mechanisms, deepen the response, and achieve molecular remissions.
The development, safety and efficacy of pacritinib for the treatment of myelofibrosis
Dysregulation of janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been described in myelofibrosis and pacritinib, a selective JAK2/FLT3 inhibitor has shown promising results, without significant thrombocytopenia.
The evolving treatment paradigm in myelofibrosis
  • R. Mesa
  • Medicine
    Leukemia & lymphoma
  • 2013
Discovery of the Janus kinase 2 (JAK2) gain-of-function mutation, JAK2V617F, in the majority (50–60%) of patients with MF led to increased understanding of the biology underlying MF and the development of Jak2 inhibitors to treat MF.