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DRUG:

Vonjo (pacritinib)

i
Other names: SB 1518, ONX 0803, BAX 2201, SB1518, SB-1518, ONX-0803, BAX-2201, BAX2201, ONX0803
Company:
SOBI
Drug class:
JAK2 inhibitor, FLT3 inhibitor, CSF-1R inhibitor, ACVR1 inhibitor, IRAK-1 inhibitor
Related drugs:
6d
BLAST: Pacritinib for Biochemical Relapse After Definitive Treatment for Prostate Cancer (clinicaltrials.gov)
P2, N=6, Terminated, Medical College of Wisconsin | Trial completion date: May 2027 --> Oct 2024 | Active, not recruiting --> Terminated; After 6 patients were enrolled, it was determined that only patients with STAT5 activation were having a biochemical response to pacritinib treatment.
Trial completion date • Trial termination
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Vonjo (pacritinib)
10d
New P1 trial • Combination therapy
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Vonjo (pacritinib)
24d
Spatial-transcriptomic profiling: a new lens for understanding myelofibrosis pathophysiology. (PubMed, Cell Commun Signal)
Current therapeutic strategies include JAK inhibitors like Ruxolitinib, which target the JAK-STAT pathway, alongside supportive treatments such as blood transfusions, erythropoiesis-stimulating agents and developing combinatorial approaches...Recently approved JAK inhibitors, including Fedratinib, Pacritinib, and Momelotinib, have expanded the therapeutic landscape...These technologies elucidate the role of the spleen in MF, highlighting its transformation into a site of abnormal hematopoietic activity, fibrotic changes, and immune cell infiltration, functioning as a "tumor surrogate." By profiling diverse cell populations and molecular alterations within the BM and spleen, SRT facilitates a deeper understanding of MF pathophysiology, helping identify novel therapeutic targets and biomarkers. Ultimately, integrating spatial transcriptomics into MF research promises to enhance diagnostic precision and therapeutic innovation, addressing the multifaceted challenges of this disease.
Review • Journal
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TP53 (Tumor protein P53) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • TNFA (Tumor Necrosis Factor-Alpha) • SRSF2 (Serine and arginine rich splicing factor 2) • TGFB1 (Transforming Growth Factor Beta 1) • CALR (Calreticulin)
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TP53 mutation • TET2 mutation • SRSF2 mutation
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
1m
Pacritinib Response Is Associated With Overall Survival in Myelofibrosis: PERSIST-2 Landmark Analysis of Survival. (PubMed, Eur J Haematol)
In patients with myelofibrosis and platelets ≤ 100 × 109/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781.
Journal
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JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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Jakafi (ruxolitinib) • Vonjo (pacritinib)
1m
High-throughput screening identified pacritinib as a promising therapeutic approach to overcome lenvatinib resistance in hepatocellular carcinoma by targeting IRAK1. (PubMed, Biochem Biophys Res Commun)
Interestingly, pacritinib, but not other JAK inhibitors such as ruxolitinib, upadacitinib, or filgotinib, acted synergistically with lenvatinib in HCC cells. Immunohistochemical analysis of tumor sections revealed that pacritinib reduced Ki67 staining and phosphorylated IRAK1. Our findings suggest that pacritinib may be a promising therapeutic option for the treatment of advanced HCC, particularly in patients who have developed resistance to lenvatinib.
Journal
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IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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Lenvima (lenvatinib) • Jakafi (ruxolitinib) • Vonjo (pacritinib)
1m
How I individualize selection of JAK inhibitors for patients with myelofibrosis. (PubMed, Blood)
Ruxolitinib and fedratinib can cause myelosuppression and are recommended for patients with myeloproliferative MF. Approval of 2 less myelosuppressive JAKi, pacritinib and momelotinib, provided essential treatment options for patients with severe thrombocytopenia and anemia, respectively...Judicious treatment decisions of JAKi can be made with in-depth understanding of the pivotal clinical trials on JAKi and their therapeutic attributes and should be guided by the dominant clinical manifestations and the type/degree of cytopenia(s). This article reviews our clinical approach to treatment with JAKi and their sequencing in MF patients by presenting 3 clinical vignettes.
Journal
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ACVR1 (Activin A Receptor Type 1)
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
2ms
Muti-target rationale design of novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates as telomerase/JAK1/STAT3/TLR4 inhibitors: In vitro and in vivo investigations. (PubMed, Bioorg Chem)
In this work, additional effort was applied to design new BIBR1532-based analogues with potential inhibitory activity against telomerase and acting as multitarget antitumor candidates to overcome the resistance problem...Compound 4l represented a very promising JAK1 inhibitory potential with a 0.46-fold change, compared to that of pacritinib reference standard (0.33-fold change). Besides, it showed a superior STAT3-inhibitory potential with a 0.22-fold change compared to sorafenib (0.33-fold change). Additionally, compound 4l downregulated TLR4 protein expression by 0.81-fold change compared to that of resatorvid (0.29-fold change)...Remarkably, compound 4l led to prominent reductions in tumor size and mass. Concurrent enhancements in biochemical, hematologic, histopathologic, and immunohistochemical parameters further confirmed the suppression of angiogenesis and inflammation, elucidating additional mechanisms by which compound 4l exerts its anticancer effects.
Preclinical • Journal
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JAK1 (Janus Kinase 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • TLR4 (Toll Like Receptor 4)
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sorafenib • Vonjo (pacritinib) • BIBR1532
2ms
JAK inhibitors for myelofibrosis: ruxolitinib and momelotinib (PubMed, Rinsho Ketsueki)
Pacritinib (not approved in Japan) is suitable for MF patients with thrombocytopenia. JAK inhibitor selection and supportive care by ESA or danazol in lieu of transfusion should be considered. Many classes of drugs other than JAK inhibitors for myelofibrosis are under investigation.
Journal
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JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1) • CALR (Calreticulin)
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • Ojjaara (momelotinib)
3ms
Enrollment open
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CRP (C-reactive protein)
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Vonjo (pacritinib)
3ms
New P1 trial
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Vonjo (pacritinib)
4ms
JAK2/mTOR Inhibition Fails to Prevent Acute GVHD Despite Reduced Th1/Th17 cells: Final Phase II Trial Results. (PubMed, Blood)
Our phase I graft-versus-host disease (GVHD) prevention trial of JAK2 inhibitor, pacritinib, (recommended phase II dose: 100mg po BID day 0 to +70) plus sirolimus and tacrolimus (PAC/SIR/TAC) demonstrated the regimen was safe and free of pan-JAK myelosuppression after allogeneic hematopoietic cell transplantation (alloHCT). The cumulative incidence of grade II-IV acute GVHD by day +100 with PAC/SIR/TAC was similar to historic SIR/TAC values (46 v 43%). While PAC/SIR/TAC suppressed pSTAT3 and Th1/Th17 cells, the regimen did not improve acute GVHD prevention.
P2 data • Journal
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JAK2 (Janus kinase 2) • IL6 (Interleukin 6) • CD4 (CD4 Molecule) • IL2 (Interleukin 2)
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sirolimus • Vonjo (pacritinib)
4ms
Study of Bemcentinib Plus Pacritinib In Patients With Advanced Lung Adenocarcinoma (clinicaltrials.gov)
P1/2, N=44, Not yet recruiting, The University of Texas Health Science Center at San Antonio
New P1/2 trial • Metastases
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Keytruda (pembrolizumab) • erlotinib • docetaxel • bemcentinib (BGB324) • Vonjo (pacritinib)
4ms
Consistency of Spleen and Symptom Reduction Regardless of Cytopenia in Patients With Myelofibrosis Treated With Pacritinib. (PubMed, Clin Lymphoma Myeloma Leuk)
Pacritinib demonstrates consistent efficacy in patients with MF regardless of baseline platelet and hemoglobin counts.
Journal
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JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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Vonjo (pacritinib)
5ms
Study to Evaluate the Safety, Tolerability, and PK of Pacritinib (clinicaltrials.gov)
P1, N=29, Completed, CTI BioPharma | Recruiting --> Completed
Trial completion
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Vonjo (pacritinib)
5ms
Pacritinib in CMML (clinicaltrials.gov)
P1/2, N=26, Recruiting, Douglas Tremblay | Not yet recruiting --> Recruiting | Initiation date: Jan 2024 --> Sep 2024
Enrollment open • Trial initiation date • Combination therapy
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azacitidine • Vonjo (pacritinib)
5ms
Dual Inhibition of the TrkA and JAK2 pathways using Entrectinib and Pacritinib suppresses the growth and metastasis of HER2-positive and triple-negative breast cancers. (PubMed, Cancer Lett)
Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells...The Entrectinib-Pacritinib combination suppressed orthotopic growth of HER2-positive Trastuzumab-refractory breast cancer xenografts and basal patient-derived xenograft (PDXs), reduced tumoral SOX2 and MYC, and induced apoptosis in both mouse models. The Entrectinib-Pacritinib combination inhibited overall metastatic burden, and brain and bone metastases of intracardially inoculated TNBC cells without toxicity. Together, our results demonstrate for the first time that co-inhibition of TrkA and JAK2 synergistically suppresses breast cancer growth and metastasis, thereby providing preclinical evidence that supports future clinical evaluations.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • SOX2
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Herceptin (trastuzumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Jakafi (ruxolitinib) • Vonjo (pacritinib)
5ms
Functional and Structural Characterization of Clinical-Stage Janus Kinase 2 Inhibitors Identifies Determinants for Drug Selectivity. (PubMed, J Med Chem)
Ruxolitinib, fedratinib, momelotinib, and pacritinib are FDA-/EMA-approved JAK inhibitors effective in relieving symptoms in MPN patients but show variable clinical profiles due to poor JAK selectivity. Inhibitors differed in their JAK isoform selectivity and potency for erythropoietin signaling, but their general cytokine inhibition signatures in blood cells were comparable. Structural data indicate that high potency and moderate JAK2 selectivity can be obtained by targeting the front pocket of the adenosine 5'-triphosphate-binding site.
Journal
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JAK2 (Janus kinase 2)
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
5ms
Enrollment open
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Jakafi (ruxolitinib) • Xpovio (selinexor) • Vonjo (pacritinib) • Ojjaara (momelotinib)
5ms
Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials. (PubMed, Front Pharmacol)
We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023...The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h. FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.
Review
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FLT3 (Fms-related tyrosine kinase 3)
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sorafenib • sunitinib • Xospata (gilteritinib) • Cabometyx (cabozantinib tablet) • Rydapt (midostaurin) • Vanflyta (quizartinib) • crenolanib (ARO-002) • tandutinib (MLN518) • Turalio (pexidartinib) • famitinib (SHR 1020) • mivavotinib (CB-659) • Vonjo (pacritinib) • lestaurtinib (CEP-701)
6ms
Recent Advances in IRAK1: Pharmacological and Therapeutic Aspects. (PubMed, Molecules)
Various IRAK1 inhibitors, including Pacritinib and Rosoxacin, show therapeutic potential against malignancies and inflammatory diseases...Additionally, the emergence of selective IRAK1 degraders, such as JNJ-101, provides a novel strategy by targeting the scaffolding function of IRAK1. Thus, the evolving landscape of IRAK1-targeted approaches provides promising avenues for increasingly safe and effective therapeutic interventions for various diseases.
Review • Journal
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IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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Vonjo (pacritinib)
7ms
Pacritinib w/ Talazoparib in Pts w/ Myeloproliferative Neoplasms Unresponsive to JAK2 Inhibition (clinicaltrials.gov)
P1, N=24, Recruiting, Fox Chase Cancer Center | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy
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Talzenna (talazoparib) • Vonjo (pacritinib)
7ms
miR-146a-/- mice model reveals that NF-κB inhibition reverts inflammation-driven myelofibrosis-like phenotype. (PubMed, Am J Hematol)
Furthermore, tailoring treatment with currently available JAK inhibitors (such as ruxolitinib or fedratinib) does not modify the natural history of the disease and has important limitations, including cytopenias...Specifically, we tested the JAK1/2 inhibitor, ruxolitinib; the NF-κB inhibitor via IKKα/β, BMS-345541; both inhibitors in combination; or a dual inhibitor of both pathways (JAK2/IRAK1), pacritinib...Additionally, combined treatment reduced both COL1A1 and IL-6 production in an in vitro model mimicking JAK2-driven fibrosis. In conclusion, NF-κB inhibition reduces, in vitro and in vivo, disease burden and BM fibrosis, which could provide benefits in myelofibrosis patients.
Preclinical • Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • COL1A1 (Collagen Type I Alpha 1 Chain) • IL1B (Interleukin 1, beta) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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JAK2 V617F
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • BMS-345541 • Inrebic (fedratinib)
8ms
Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms (clinicaltrials.gov)
P2, N=25, Recruiting, University of Washington | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2026
Trial completion date • Trial primary completion date • Combination therapy
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azacitidine • Jakafi (ruxolitinib) • decitabine • Vonjo (pacritinib) • Inrebic (fedratinib)
9ms
Pacritinib inhibits proliferation of primary effusion lymphoma cells and production of viral interleukin-6 induced cytokines. (PubMed, Sci Rep)
Finally, pacritinib suppressed KSHV viral IL-6-induced human IL-6 and IL-10 production in peripheral blood mononuclear cells, which may model an important step in KSHV-MCD pathogenesis. These results suggest that pacritinib warrants testing for the treatment of KSHV-MCD and PEL.
Journal
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FLT3 (Fms-related tyrosine kinase 3) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IL6 (Interleukin 6) • IL10 (Interleukin 10) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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Vonjo (pacritinib)
9ms
ADCT-602, a novel PBD dimer-containing antibody-drug conjugate for treating CD22-positive hematological malignancies. (PubMed, Mol Cancer Ther)
Combining ADCT-602 + pacritinib was beneficial in ADCT-602-resistant cells. Chidamide increased CD22 expression on B-cell tumor surfaces, increasing ADCT-602 activity. These data support clinical testing of ADCT-602 in R/R B-ALL (NCT03698552) and CD22-positive hematological cancers.
Journal
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CD22 (CD22 Molecule) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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CD22 positive • CD22 expression
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Epidaza (chidamide) • Vonjo (pacritinib) • epratuzumab-cys-tesirine (ADCT-602)
9ms
Trial completion
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Vonjo (pacritinib) • midazolam hydrochloride
9ms
BLAST: Pacritinib for Biochemical Relapse After Definitive Treatment for Prostate Cancer (clinicaltrials.gov)
P2, N=6, Active, not recruiting, Medical College of Wisconsin | Recruiting --> Active, not recruiting
Enrollment closed
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Vonjo (pacritinib)
10ms
New P1 trial • Combination therapy
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Talzenna (talazoparib) • Vonjo (pacritinib)
10ms
ACVR1: A Novel Therapeutic Target to Treat Anemia in Myelofibrosis. (PubMed, Cancers (Basel))
Among the approved JAK inhibitors (ruxolitinib, fedratinib, momelotinib, and pacritinib) for MF, momelotinib and pacritinib are preferably used in cytopenic patients; both agents are potent ACVR1 inhibitors that suppress hepcidin expression via the BMP6/ACVR1/SMAD pathway and restore iron homeostasis/erythropoiesis...Zilurgisertib (ACVR1 inhibitor) and DISC-0974 (anti-hemojuvelin monoclonal antibody) are evaluated in early phase clinical trials in patients with MF and anemia. Luspatercept (ACVR2B ligand trap) is assessed in transfusion-dependent MF patients in a registrational phase 3 trial. Approved ACVR1 inhibitors and novel agents in development are poised to improve the outcomes of anemic MF patients.
Review • Journal
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ACVR1 (Activin A Receptor Type 1) • BMP6 (Bone Morphogenetic Protein 6) • ACVR2B (Activin A Receptor Type 2B)
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Jakafi (ruxolitinib) • Reblozyl (luspatercept-aamt) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib) • zilurgisertib (INCB00928)
11ms
Momelotinib expands the therapeutic armamentarium for myelofibrosis: Impact on hierarchy of treatment choices. (PubMed, Am J Hematol)
The primary objective of treatment in myelofibrosis (MF) is prolongation of life, which is currently accomplished only by allogeneic hematopoietic stem cell transplantation (AHSCT). Pacritinib and fedratinib provide alternative options in the presence of severe thrombocytopenia or ruxolitinib-resistance/intolerance, respectively. Splenectomy remains a viable option for drug-resistant symptomatic splenomegaly and cytopenia.
Review • Journal
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JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1)
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
11ms
Treatment of anemia in myelofibrosis: focusing on Novel Therapeutic Options. (PubMed, Expert Opin Investig Drugs)
This review summarizes novel and promising treatments for anemia in myelofibrosis including transforming growth factor-β inhibitors luspatercept and KER-050, JAK inhibitors momelotinib, pacritinib, and jaktinib, BET inhibitors pelabresib and ABBV-744, antifibrotic PRM-151, BCL2/BCL-XL inhibitor navitoclax, and telomerase inhibitor imetelstat. Standard approaches to treat myelofibrosis-related anemia have limited efficacy and are associated with toxicity. New drugs have shown positive results in myelofibrosis-associated anemia when used alone or in combination.
Review • Journal
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BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
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navitoclax (ABT 263) • ABBV-744 • Reblozyl (luspatercept-aamt) • Vonjo (pacritinib) • Ojjaara (momelotinib) • pelabresib (DAK539) • Rytelo (imetelstat) • elritercept (KER-050) • zinpentraxin alfa (RG6354)
11ms
Pacritinib in CMML (clinicaltrials.gov)
P1/2, N=26, Not yet recruiting, Douglas Tremblay
New P1/2 trial • Combination therapy
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azacitidine • Vonjo (pacritinib)
12ms
Comparing Common Therapies in Polycythemia Vera (PV): A Disproportionality Analysis in the FDA Adverse Event Reporting System (FAERS) Database (ASH 2023)
Background: Prior to the approval of ropeginterferon alfa-2b-njft (ropeginterferon) in November 2021, the alternatives to hydroxyurea for the treatment of polycythemia vera (PV) included Janus Kinase inhibitors (JAKi) and older versions of recombinant interferon-alpha (rIFNα). This study examined FAERS reports to detect disproportional reporting odds of drug-associated AEs severity and SOCs in four PV treatments: ropeginterferon, ruxolitinib, interferon alfa-2a, and pacritinib. Ropeginterferon had a significant ROR for non-serious AEs. Peginterferon alfa-2a demonstrated a significant ROR for SAEs.
Adverse events
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IFNA1 (Interferon Alpha 1)
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • hydroxyurea • Besremi (ropeginterferon alfa-2b-njft)
12ms
Activity of Selinexor As a Single Agent and Synergistic Activity with Approved/Investigational Myelofibrosis Therapies in Vitro (ASH 2023)
Despite the current standard of care, the JAK1/2 inhibitor (JAKi) ruxolitinib (RUX), a significant unmet need remains for patients (pts) with MF, due to lack of response or JAKi resistance... JAK2V617F mutant cell lines HEL ( TP53M113K), UKE-1 ( TP53WT), MUTZ-8 ( TP53WT), and JAK2WT ELF-153 ( TP53I251N) cells were treated with SEL alone or in combination with RUX, pacritinib (PAC), momelotinib (MMB), pelabresib (PELA), or navitoclax (NAV)... In a panel of MPN-derived cells with or without JAK2V617F, SEL showed single-agent antiproliferative activity, and synergism with other MF therapeutics at clinically achievable concentrations through regulation of XPO1, JAK/STAT signaling, and apoptosis/senescence regulators. In addition to positive Phase 1 clinical data in pts with JAKi-naïve MF who received SEL with RUX, these preclinical data support synergistic activity between SEL and other MF therapies, suggesting the potential for SEL as a backbone for novel treatment combinations for MF.
Preclinical • PARP Biomarker • IO biomarker
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CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • CALR (Calreticulin) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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TP53 mutation • TP53 wild-type • MYC expression • CCND1 expression • JAK2 V617F • JAK2 mutation
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Jakafi (ruxolitinib) • Xpovio (selinexor) • navitoclax (ABT 263) • Vonjo (pacritinib) • Ojjaara (momelotinib) • pelabresib (DAK539)
12ms
Tagraxofusp Shows Promising Anti-Tumoral Efficacy in Preclinical in Vitro Models of Myelofibrosis, Both As a Single Agent and in Combination with Janus Kinase Inhibitors (ASH 2023)
The role of the JAK/Signal transducer and activator of transcriptions (STAT) pathway in MF has led to the recent approval of three different JAK2 inhibitors (ruxolitinib, pacritinib, and fedratinib) for MF treatment. Our studies showed high sensitivity of MF cell lines to tagraxofusp as a single agent, which is expected given phase 2 results demonstrated clinical efficacy of single-agent tagraxofusp in R/R MF (Yacoub et al. ASH 2021). In addition, synergism was observed in combination with JAK inhibitors.
Preclinical • Combination therapy
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • JAK2 V617F • CD123 expression • IL3RA expression • IL3RA positive
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Jakafi (ruxolitinib) • Elzonris (tagraxofusp-erzs) • Vonjo (pacritinib) • Inrebic (fedratinib)
almost1year
Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in Refractory Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (clinicaltrials.gov)
P1/2, N=50, Recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024
Trial completion date • Trial primary completion date
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Vonjo (pacritinib)
1year
Enhanced synergy of pacritinib with temsirolimus and sunitinib in preclinical renal cell carcinoma model by targeting JAK2/STAT pathway. (PubMed, J Chemother)
Interestingly, pacritinib exhibited synergistic effects when combined with temsirolimus and sunitinib, but antagonistic effects when combined with doxorubicin, in a panel of RCC cell lines. Mechanistic studies indicated that the inhibition of JAK2, but not IRAK, was the main contributor to the anti-RCC activity of pacritinib. Our study is the first to demonstrate that pacritinib shows promise as a treatment option for RCC and underscores the therapeutic potential of targeting the JAK2/STAT signalling pathway in RCC.
Preclinical • Journal
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FLT3 (Fms-related tyrosine kinase 3) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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sunitinib • doxorubicin hydrochloride • Torisel (temsirolimus) • Vonjo (pacritinib)
1year
Platelet Response in Pacritinib-Treated Patients with Cytopenic Myelofibrosis: A Retrospective Analysis of PERSIST-2 and PAC203 Studies (ASH 2023)
Thrombocytopenia is both prognostic of poor outcomes and predictive of treatment intolerance with the JAK1/2 inhibitor ruxolitinib, which exacerbates cytopenias. Of 117 patients randomized to pacritinib (75 from PERSIST-2, 42 from PAC203), 16% (n=19) experienced HI-P on study (as defined in methods). Additionally, 14 of the 19 HI-P patients had sustained platelet improvement over ≥12 weeks). By contrast, only 5% (4/77) of patients on BAT achieved HI-P response prior to end of study treatment.
Retrospective data
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ACVR1 (Activin A Receptor Type 1) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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JAK2 V617F
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Jakafi (ruxolitinib) • Vonjo (pacritinib)
1year
Retrospective Analysis of the Relationship between Transfusion Independence and Bone Marrow Fibrosis Reduction in Patients with Myelofibrosis Treated with Pacritinib Versus Ruxolitinib (ASH 2023)
In cytopenic MF patients from PERSIST-2, TI-R on pacritinib was associated with BMF improvement. Though these results are based on a small sample size, they contrast with recent data suggesting no correlation between BMF reduction and TI-R on the JAK1/2 inhibitors momelotinib and ruxolitinib (Oh ST, et al. Blood 2022; 140 (Supp 1):821-23).
Retrospective data
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ACVR1 (Activin A Receptor Type 1) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • Ojjaara (momelotinib)
1year
Type 1/like Calr Mutation in Momelotinib-Treated Patients with Myelofibrosis Is the Most Prominent Predictor of Drug Survival and Longevity without Transplant (ASH 2023)
FDA-approved JAKi for the treatment of MF include ruxolitinib, fedratinib, and pacritinib. CALR-1 mutation is the most important risk factor for both drug survival and longevity without AHSCT, in momelotinib-treated patients with MF. Such information might help identify MF patients who might benefit from treatment with momelotinib and in whom AHSCT might be deferred or not.
Clinical
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JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • CALR (Calreticulin)
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ASXL1 mutation • SRSF2 mutation • CALR mutation
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Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)