^
7d
Longitudinal Assessment of Transfusion Intensity in Patients With JAK Inhibitor-Naive or -Experienced Myelofibrosis Treated With Momelotinib. (PubMed, Clin Lymphoma Myeloma Leuk)
These novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators.
Journal
|
JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Ojjaara (momelotinib)
1m
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
|
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)
|
TP53 mutation • TET2 mutation • SRSF2 mutation
|
Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
2ms
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
|
ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
3ms
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
|
JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1) • CALR (Calreticulin)
|
Jakafi (ruxolitinib) • Vonjo (pacritinib) • Ojjaara (momelotinib)
3ms
Momelotinib in myelofibrosis and beyond: a comprehensive review of therapeutic insights in hematologic malignancies. (PubMed, Discov Oncol)
Additionally, we explore the application of Momelotinib in other cancer types and investigate predictors for treatment success. Furthermore, we examine the utilization of Momelotinib in patients with liver and kidney failure.
Review • Journal
|
JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1)
|
Ojjaara (momelotinib)
3ms
Momelotinib: Mechanism of action, clinical, and translational science. (PubMed, Clin Transl Sci)
While currently approved Janus kinase (JAK) inhibitors (ruxolitinib, fedratinib) improve splenomegaly and symptoms, most can exacerbate myelofibrosis-related anemia, a negative prognostic factor for survival. This review describes momelotinib's mechanism of action, detailing how the JAK-STAT pathway is involved in myelofibrosis pathogenesis and ACVR1 inhibition decreases hepcidin, leading to improved erythropoiesis. Additionally, it summarizes the pivotal studies and data that informed the recommended dosage and risk/benefit assessment.
Review • Journal
|
JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
|
Jakafi (ruxolitinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
4ms
Momelotinib versus ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis: an efficacy/safety analysis in the Japanese subgroup of the phase 3 randomized SIMPLIFY-1 trial. (PubMed, Int J Hematol)
Grade 3/4 TRAE rates were 0% and 55.6%, with specific events being anemia (55.6%) and vertigo (11.1%) with ruxolitinib. Momelotinib was well tolerated, improved spleen and symptom responses, and reduced transfusion requirements in Japanese patients with JAKi-naïve MF.
P3 data • Journal
|
ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Ojjaara (momelotinib)
4ms
MoReLife - real-life data support the potential of momelotinib as a safe and effective treatment option for cytopenic myelofibrosis patients. (PubMed, Ann Hematol)
Whereas the latter are usually addressed by the JAK1/2 inhibitors ruxolitinib and fedratinib, cytopenias often remain critical. 5 patients stopped treatment due to side effects (8%), 6 patients due to a worsening of clinical symptoms (10%). Taken together, the MoReLife analysis identifies momelotinib as potent and safe therapeutic option also for heavily pre-treated cytopenic MF patients under real world conditions.
Journal
|
ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
4ms
New P2 trial • Combination therapy
|
Reblozyl (luspatercept-aamt) • Ojjaara (momelotinib)
4ms
Japanese regulatory • Journal
|
MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
|
Retevmo (selpercatinib) • Jaypirca (pirtobrutinib) • Haiyitan (gumarontinib) • Ezharmia (valemetostat) • Ojjaara (momelotinib) • Targretin oral (bexarotene oral)
4ms
Momelotinib versus Continued Ruxolitinib or Best Available Therapy in JAK Inhibitor-Experienced Patients with Myelofibrosis and Anemia: Subgroup Analysis of SIMPLIFY-2. (PubMed, Adv Ther)
In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies.
Journal
|
JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
4ms
Momelotinib - a promising advancement in the management of myelofibrosis in adults with anemia. (PubMed, Front Oncol)
The MOMENTUM trial compared MMB to danazol in JAK inhibitor-treated MF patients with anemia, showing MMB's superior symptom relief and transfusion independence rates. Additionally, the SIMPLIFY-1 and SIMPLIFY-2 trials evaluated MMB in JAK inhibitor-naïve and experienced patients, respectively, confirming MMB's non-inferiority to ruxolitinib in spleen volume reduction and highlighting its benefits in transfusion requirements...These trials collectively suggest MMB as an effective treatment for MF, improving quality of life and offering a survival advantage for patients with anemia. Despite challenges, such as trial design limitations and adverse events, MMB represents a significant advancement in MF management, providing a new therapeutic option for a previously underserved patient population.
Review • Journal
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1) • CALR (Calreticulin)
|
Jakafi (ruxolitinib) • Ojjaara (momelotinib)
6ms
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
|
JAK2 (Janus kinase 2)
|
Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
6ms
Discovery of a potent and selective JAK1-targeting PROTAC degrader with anti-tumor activities. (PubMed, Bioorg Med Chem Lett)
Herein, a series of CRBN-directed JAK-targeting PROTACs were designed and synthesized utilizing a JAK1/JAK2 dual inhibitor-momelotinib as the warhead...Moreover, PROTAC 10c significantly suppressed JAK1 and its key downstream signaling. Together, compound 10c may serve as a novel lead compound for antitumor drug discovery.
Journal
|
JAK2 (Janus kinase 2) • CRBN (Cereblon) • JAK1 (Janus Kinase 1)
|
Ojjaara (momelotinib)
6ms
Enrollment open
|
Jakafi (ruxolitinib) • Xpovio (selinexor) • Vonjo (pacritinib) • Ojjaara (momelotinib)
6ms
BBI-TP-3654-102: A Study of Oral TP-3654 in Patients With Myelofibrosis (clinicaltrials.gov)
P1/2, N=240, Recruiting, Sumitomo Pharma America, Inc. | N=80 --> 240 | Trial completion date: Feb 2025 --> Apr 2030 | Trial primary completion date: Dec 2024 --> Apr 2027
Enrollment change • Trial completion date • Trial primary completion date
|
Jakafi (ruxolitinib) • nuvisertib (TP-3654) • Ojjaara (momelotinib)
6ms
Enrollment open
|
Xospata (gilteritinib) • Ojjaara (momelotinib)
7ms
Clinical assessment of momelotinib drug-drug interactions via CYP3A metabolism and transporters. (PubMed, Clin Transl Sci)
Momelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively)...Safety findings were mild in this short-term study in healthy volunteers. This analysis suggests that momelotinib interactions with OATP1B1/1B3 inhibitors and BCRP substrates may warrant monitoring for adverse reactions or dose adjustments.
Journal
|
CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
|
Ojjaara (momelotinib) • midazolam hydrochloride • rifampicin • ritonavir
7ms
Momelotinib in myelofibrosis. (PubMed, Expert Opin Pharmacother)
Recent years have seen the emergence of novel therapeutic agents, notably ruxolitinib and fedratinib, which target the Janus kinases (JAK) pathway. Due to its mechanism of action, MMB represents a valuable therapeutic option in MF, addressing the clinical challenge of anemia and potentially improving outcomes for patients with hematologic malignancies. Ongoing research explores MMB's potential in acute myeloid leukemia and combination therapies.
Review • Journal
|
ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
8ms
Momelotinib vs. ruxolitinib in myelofibrosis patient subgroups by baseline hemoglobin levels in the SIMPLIFY-1 trial. (PubMed, Leuk Lymphoma)
No new or unexpected safety signals were identified. Overall, momelotinib provides spleen, symptom, and anemia benefits to JAK inhibitor-naive patients with myelofibrosis regardless of baseline hemoglobin level, and greater anemia-related benefits vs. ruxolitinib in patients with hemoglobin <12 g/dL.
Journal
|
JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Ojjaara (momelotinib)
10ms
Anemia-related response end points in myelofibrosis clinical trials: current trends and need for renewed consensus. (PubMed, Future Oncol)
Here we apply our experiences in the phase III trials of momelotinib, a JAK1/JAK2/ACVR1 inhibitor and the first therapy indicated by the US FDA for myelofibrosis patients with anemia, to highlight how application of different criteria impacts the anemia-related benefits reported for any potential treatment in myelofibrosis. We advocate for a convention of a new expert consensus panel to bring consistency and transparency to the definition of anemia-related response in myelofibrosis.
Review • Journal
|
JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1)
|
Ojjaara (momelotinib)
10ms
New P1/2 trial
|
Xospata (gilteritinib) • Ojjaara (momelotinib)
10ms
Properties of FDA-approved small molecule protein kinase inhibitors: a 2024 update. (PubMed, Pharmacol Res)
Six drugs (abrocitinib, baricitinib, deucravacitinib, ritlecitinib, tofacitinib, upadacitinib) are used for the treatment of inflammatory diseases (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, and ulcerative colitis)...The following seven drugs received FDA approval in 2023: capivasertib (HER2-positive breast cancer), fruquintinib (metastatic colorectal cancer), momelotinib (myelofibrosis), pirtobrutinib (mantle cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma), quizartinib (Flt3-mutant acute myelogenous leukemia), repotrectinib (ROS1-positive lung cancer), and ritlecitinib (alopecia areata). All of the FDA-approved drugs are orally effective with the exception of netarsudil, temsirolimus, and trilaciclib. This review summarizes the physicochemical properties of all 80 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, polar surface area, potency, solubility, lipophilic efficiency, and ligand efficiency.
FDA event • Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • FLT3 (Fms-related tyrosine kinase 3) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
|
HER-2 positive • FLT3 mutation • ROS1 positive
|
Vanflyta (quizartinib) • Torisel (temsirolimus) • Truqap (capivasertib) • Augtyro (repotrectinib) • Fruzaqla (fruquintinib) • Jaypirca (pirtobrutinib) • Cosela (trilaciclib) • Ojjaara (momelotinib) • tofacitinib • Litfulo (ritlecitinib)
11ms
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
|
ACVR1 (Activin A Receptor Type 1) • BMP6 (Bone Morphogenetic Protein 6) • ACVR2B (Activin A Receptor Type 2B)
|
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
|
JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
12ms
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
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
|
navitoclax (ABT 263) • ABBV-744 • Reblozyl (luspatercept-aamt) • Vonjo (pacritinib) • Ojjaara (momelotinib) • pelabresib (DAK539) • Rytelo (imetelstat) • elritercept (KER-050) • zinpentraxin alfa (RG6354)
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
|
CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • CALR (Calreticulin) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
TP53 mutation • TP53 wild-type • MYC expression • CCND1 expression • JAK2 V617F • JAK2 mutation
|
Jakafi (ruxolitinib) • Xpovio (selinexor) • navitoclax (ABT 263) • Vonjo (pacritinib) • Ojjaara (momelotinib) • pelabresib (DAK539)
12ms
Estimating Transfusion-Related Medical Costs and Associated Time Burden in Patients with Myelofibrosis: A Comparison of Momelotinib Vs Ruxolitinib Based on Simplify-1 (ASH 2023)
Reductions in transfusion dependence and transfusion visits for MMB vs RUX were associated with projected healthcare system savings in transfusion costs and transfusion-related time burden in JAK inhibitor–naive pts with MF, including in subgroup analyses of pts aged ≥65 years.
Clinical • HEOR
|
JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Ojjaara (momelotinib)
almost1year
Momelotinib: First Approval. (PubMed, Drugs)
In September 2023, momelotinib was approved in the USA for the treatment of intermediate or high-risk MF, including primary MF or secondary MF &lsqb;post-polycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia. This article summarizes the milestones in the development of momelotinib leading to this first approval for MF.
Review • Journal
|
JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1)
|
Ojjaara (momelotinib)
1year
Momelotinib in Myelofibrosis Patients With Thrombocytopenia: Post Hoc Analysis From Three Randomized Phase 3 Trials. (PubMed, Hemasphere)
Post hoc analyses herein evaluated the efficacy and safety of momelotinib in patients with MF and thrombocytopenia (platelet counts <100 × 10/L) from randomized phase 3 studies: MOMENTUM (momelotinib versus danazol; JAK inhibitor experienced); SIMPLIFY-1 (momelotinib versus ruxolitinib; JAK inhibitor naïve); and SIMPLIFY-2 (momelotinib versus best available therapy; JAK inhibitor experienced); these studies were not statistically powered to assess differences in thrombocytopenic subgroups, and these analyses are descriptive. The safety profile of momelotinib in thrombocytopenic patients was also consistent with the overall study population. In summary, momelotinib represents a safe and effective treatment option for patients with MF and moderate-to-severe thrombocytopenia.
P3 data • Retrospective data • Journal
|
JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Ojjaara (momelotinib)
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
|
ACVR1 (Activin A Receptor Type 1) • IRAK1 (Interleukin 1 Receptor Associated Kinase 1)
|
Jakafi (ruxolitinib) • Vonjo (pacritinib) • Ojjaara (momelotinib)
1year
Estimating Transfusion-Related Medical Costs and Associated Time Burden in Patients with Myelofibrosis: A Comparison of Momelotinib Vs Ruxolitinib Based on Simplify-1 (ASH 2023)
Reductions in transfusion dependence and transfusion visits for MMB vs RUX were associated with projected healthcare system savings in transfusion costs and transfusion-related time burden in JAK inhibitor–naive pts with MF, including in subgroup analyses of pts aged ≥65 years.
Clinical • HEOR
|
JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • 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
|
JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • CALR (Calreticulin)
|
ASXL1 mutation • SRSF2 mutation • CALR mutation
|
Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
1year
Comparison of the Enzymatic and Cellular Profiles of Clinical JAK2 Inhibitors for the Treatment of Myelofibrosis (ASH 2023)
Introduction: Three Janus kinase 2 (JAK2) inhibitors (JAKinibs) have been approved by the FDA for the treatment of myelofibrosis (MF): ruxolitinib, fedratinib, and pacritinib; a fourth one, momelotinib, is currently under FDA review. JAKinibs clinically evaluated for treatment of MF exhibit distinct kinase inhibition profiles and cellular activities. Amongst the agents tested in this study, ruxolitinib was the most potent and selective JAK2 inhibitor. At concentrations several fold above clinically relevant concentrations, ruxolitinib had no observable effects on the health of cells not reliant on JAK/STAT mediated signaling.
Clinical
|
FLT3 (Fms-related tyrosine kinase 3) • JAK1 (Janus Kinase 1) • CD34 (CD34 molecule) • ACVR1 (Activin A Receptor Type 1) • TYK2 (Tyrosine Kinase 2)
|
Jakafi (ruxolitinib) • Vonjo (pacritinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
1year
Red Blood Cell Transfusion Independence Status Is an Independent Predictor of Survival: A Post Hoc Time-Dependent Analysis of the Phase 3 Simplify-1, Simplify-2, and Momentum Trials (ASH 2023)
Momelotinib (MMB) is a Janus kinase (JAK) 1/JAK2/activin A receptor type 1 (ACVR1) inhibitor that has demonstrated spleen, symptom, and anemia benefits, including increases in hemoglobin (Hb) and reduction or elimination of red blood cell (RBC) transfusion requirements in pts with MF...Analyses were performed in the safety populations of S1 (N=430; MMB vs ruxolitinib [RUX], JAK inhibitor [JAKi] naive), S2 (N=156; MMB vs best available therapy [88.5% RUX], JAKi experienced), and MOMENTUM (N=195; MMB vs danazol, JAKi experienced)... These data demonstrate that when accounting for differences in known prognostic factors and effect modifiers as well as changes in RBC transfusion status over time, a consistent and statistically significant relationship was observed between transfusion status and OS across all 3 phase 3 MMB trials. Consistent with inclusion of transfusion status in DIPSS-plus risk assessment, these data validate TI status as a clinically relevant and meaningful endpoint that is prognostic for survival in JAKi-naive and JAKi-experienced disease settings.
P3 data • Retrospective data
|
JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1)
|
JAK2 mutation
|
Jakafi (ruxolitinib) • Ojjaara (momelotinib)
1year
Longitudinal Assessment of Transfusion Intensity in Patients with JAK Inhibitor-Naive or -Experienced Myelofibrosis Treated with Momelotinib in the Phase 3 Simplify-1 and Momentum Trials (ASH 2023)
SIMPLIFY-1 included pts with JAK inhibitor–naive MF randomized (1:1) to receive MMB or ruxolitinib (RUX). In MOMENTUM, pts with symptomatic (Myelofibrosis Symptom Assessment Form Total Symptom Score ≥10), anemic (hemoglobin <10 g/dL), JAK inhibitor–experienced MF were randomized (2:1) to receive MMB or danazol (DAN)... These data demonstrate that MMB was associated with better maintenance of RBC transfusion intensity and zero RBC transfusion status vs RUX in pts with MF who were JAK inhibitor naive and showed greater reduction in RBC transfusion burden from baseline vs DAN in pts with MF who were JAK inhibitor experienced. Across both trials, ≥85% of pts treated with MMB maintained or improved transfusion intensity.
Clinical • P3 data
|
JAK2 (Janus kinase 2) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Ojjaara (momelotinib)
1year
Clinical Effectiveness and Safety of Momelotinib Compared with Continued Ruxolitinib or Best Available Therapy in Patients with Myelofibrosis Who Required RBC Transfusions: Subgroup Analysis of the Phase 3 Simplify-2 Study (ASH 2023)
While Janus kinase (JAK) inhibitors such as ruxolitinib (RUX) and fedratinib (FED) may address symptoms and splenomegaly, they do not manage and may exacerbate anemia. Treatments for anemia include erythropoiesis-stimulating agents (ESAs), often in combination with RUX or FED, and androgens such as danazol; however, these have shown limited efficacy... In RUX/BAT-treated pts with MF who required RBC transfusions, continued treatment with RUX/BAT in most pts resulted in poor treatment outcomes compared with MMB. Specifically, treatment with MMB demonstrated an ability to deliver higher SVR, TI, and TSS response rates. The lower SVR35 rate in both arms, similar to the overall ITT population, was likely a result of lack of washout from prior JAK inhibitor treatment.
Clinical • P3 data
|
JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1)
|
Jakafi (ruxolitinib) • Inrebic (fedratinib) • Ojjaara (momelotinib)
1year
FDA event
|
Ojjaara (momelotinib)
1year
Time without Transfusion Reliance or Anemia Worsening: A Novel Method for Integrating Transfusion Dependence, Anemia, and Survival with Myelofibrosis Therapies Based on the Phase 3 Simplify-1 and Simplify-2 Trials (ASH 2023)
Momelotinib (MMB), a JAK1/JAK2/activin A receptor type 1 inhibitor, has demonstrated consistent anemia benefits, including increased transfusion independence and reduced transfusion burden, as well as spleen and symptom improvements across 3 phase 3 trials in MF... Analyses were performed in the safety populations, by treatment arm, over the randomized 24-wk treatment period of SIMPLIFY-1 (n/N=430/432; MMB vs ruxolitinib [RUX], JAKi naive) and SIMPLIFY-2 (N=156; MMB vs best available therapy [BAT; 88.5% RUX], JAKi experienced)... Pts treated with MMB spent less time reliant on RBC transfusions and more time free from transfusions and anemia events, without the cost of increased AEs, compared with those treated with RUX or BAT. Given the negative QOL and prognostic impact of RBC transfusion dependence, these analyses suggest that the anemia benefits of MMB lead to improved quality of survival for pts with MF.
P3 data
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JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1)
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Jakafi (ruxolitinib) • Ojjaara (momelotinib)
1year
A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM) (clinicaltrials.gov)
P3, N=195, Completed, Sierra Oncology LLC - a GSK company | Active, not recruiting --> Completed | Trial completion date: Apr 2028 --> Dec 2022
Trial completion • Trial completion date
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Ojjaara (momelotinib)