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Aim: To estimate projected US-based cost and time burden for patients with myelofibrosis and anemia treated with momelotinib compared with danazol. Methods: Cost and time burden were calculated based on the transfusion status of patients in the MOMENTUM trial and estimates extracted from previous studies. Results: Reductions in transfusion associated with momelotinib are projected to result in cost and time savings compared with danazol in transfusion-dependent and transfusion-independent/requiring patients with myelofibrosis, respectively: annual medical costs ($53,143 and $46,455 per person), outpatient transfusion costs ($42,021 and $8,370 per person) and annual time savings (173 and 35 h per person). Conclusion: Fewer transfusions with momelotinib are projected to result in cost and time savings in patients with myelofibrosis and anemia compared with danazol. Plain Language Summary Estimated cost & time savings in patients with the blood cancer myelofibrosis Myelofibrosis is a rare blood cancer often associated with bone marrow damage, too few of some types of blood cells and symptoms including tiredness, night sweating, itching and feelings of fullness and pain because of increased spleen size. Patients with anemia (too few red blood cells) may require regular blood transfusions and this is one sign that myelofibrosis is getting worse. MOMENTUM was a Phase III clinical trial showing that the drug momelotinib was safe and effective in patients with myelofibrosis who were previously treated with a type of drug called a JAK inhibitor. In particular, the trial showed that momelotinib reduced the need for transfusions compared with danazol, another drug typically used to treat patients with anemia. Based on this transfusion information from MOMENTUM and other publicly available information about estimated medical costs and patients' time spent in receiving transfusions, the analysis described here shows that a reduction in the number of transfusions with momelotinib compared with danazol is estimated to lead to cost savings as well as reduced patient time spent in transfusion-related travel, preparing and waiting for transfusions and receiving and recovering from transfusions. Tweetable Abstract Reductions in transfusions associated with momelotinib are projected to result in savings in medical and transfusion-related costs and time burden relative to danazol in patients with myelofibrosis and anemia. Article highlights Momelotinib is a JAK1, JAK2 and ACVR1 inhibitor that targets both the complex drivers of iron-restricted anemia and chronic inflammation in MF, thereby improving constitutional symptoms and splenomegaly while also maintaining or improving Hb levels across the continuum of JAK inhibitor–naive and previously JAK inhibitor–treated patients. Transfusion dependency and moderate-to-severe anemia are critical negative prognostic factors in MF and lead to significantly higher rates of HCRU and costs in affected patients compared with non-TD patients. MOMENTUM is a randomized, double-blind study comparing momelotinib and danazol in symptomatic patients with MF and anemia who previously received JAK inhibitor therapy. Projected differences in cost and time burden associated with momelotinib relative to danazol were based on patient transfusion data from the MOMENTUM trial and cost estimates from studies using the IBM MarketScan Commercial Database and Medicare fee-for-service database as well as time burden estimates from the 2022 Knoth et al. study. Reductions in transfusions associated with momelotinib are projected to result in savings in medical and transfusion-related costs and patient time savings relative to danazol in patients with baseline TD and TI/TR status, respectively, using a terminal TI rate: annual medical costs ($53,143 and $46,455 per person), outpatient transfusion costs ($42,021 and $8,370 per person) and time savings (173 and 35 h per person). Projected savings in total annual medical costs with momelotinib relative to danazol were also shown using a rolling TI rate in patients with baseline TD and TI/TR status ($23,780 and $39,305). Projected savings in transfusion-related costs and patient time savings with momelotinib relative to danazol were also observed for patients aged ≥65 years. The results of this analysis demonstrate that momelotinib not only addresses a high unmet need in patients with MF-associated anemia but may also provide medical cost and time savings for patients by reducing their transfusion dependency. [ABSTRACT FROM AUTHOR]

JAK inhibitors are the current standard of care in myelofibrosis, but many do not address and may worsen anemia; thus, anemia-related responses have traditionally been overlooked as efficacy end points in pivotal clinical trials, leading to a lack of consistency and analytic detail in their reporting. 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. Anemia (too few healthy red blood cells) is common in patients with myelofibrosis. While it is becoming more common to measure the anemia benefits associated with potential treatments for myelofibrosis in clinical trials, different definitions of anemia benefit are available. This Perspective reviews these definitions, the differences between them, and why consistency and clarity in measuring anemia benefit matter. The definitions used in clinical trials of momelotinib, a treatment for patients with myelofibrosis and anemia, are also explained to show how the anemia benefit observed in these trials could have changed if different definitions were used. Definitions of anemia benefit may include the number of red blood cell transfusions a patient receives, the amount of hemoglobin (a red blood cell protein) in their blood, or a combination thereof. Considerations such as timing, the types of patients included, and other factors are not consistent across definitions and not always clearly reported. Results when different definitions of anemia benefit were followed in the momelotinib clinical trials show that the amount of benefit observed with treatments changes depending on which definition is used. More consistency and clarity in the definitions of anemia benefit in myelofibrosis clinical trials are needed, suggesting that a new panel of experts should come together to discuss this topic. Klencke et al. discuss the need for consensus in anemia-related response end points in myelofibrosis clinical trials, highlighting the varying definitions, key considerations, and resulting impacts on reported anemia benefits [ABSTRACT FROM AUTHOR]

Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly, debilitating constitutional symptoms and bone marrow failure. Disease-related anemia is common and associated with an inferior quality of life and survival. Unfortunately, few therapies exist to improve hemoglobin in myelofibrosis patients. Momelotinib is a JAK1/JAK2 inhibitor that also antagonizes ACVR1, leading to downregulation of hepcidin expression and increased availability of iron for erythropoiesis. In clinical testing, momelotinib has demonstrated a unique ability to improve hemoglobin and reduce transfusion burden in myelofibrosis patients with baseline anemia, while producing reductions in spleen size and symptom burden. This review explores the preclinical rationale, clinical trial data and future role of momelotinib in the evolving therapeutic landscape of myelofibrosis. [ABSTRACT FROM AUTHOR]

Hallmark features of myelofibrosis (MF) are cytopenias, constitutional symptoms and splenomegaly. Anemia and transfusion dependency are among the most important negative prognostic factors and are exacerbated by many JAK inhibitors (JAKi). Momelotinib (MMB) has been investigated in over 820 patients with MF and possesses a pharmacological and clinical profile differentiated from other JAKi by inhibition of JAK1, JAK2 and ACVR1. MMB is designed to address the complex drivers of iron-restricted anemia and chronic inflammation in MF and should improve constitutional symptoms and splenomegaly while maintaining or improving hemoglobin in JAKi-naive and previously JAKi-treated patients. The MOMENTUM Phase III study is designed to confirm and extend observations of safety and clinical activity of MMB. [ABSTRACT FROM AUTHOR]

Myelofibrosis (MF) is a chronic malignancy of the blood-forming system caused by hyperactivation of JAK2/STAT signaling pathway. Small-molecule inhibitors of JAK2 can variably ameliorate MF-related symptoms caused by chronic inflammation and hepatosplenomegaly. Anemia is a significant problem and adverse prognostic factor in over a third of MF patients and is often worsened by JAK2 inhibitors. The JAK1/2 inhibitor momelotinib unexpectedly resulted in reduction of anemia in MF patients during Phase I/II trials. Current Phase III trials will be the basis for seeking regulatory approval of momelotinib during 2017. Studies to determine how momelotinib improves anemia are underway, potentially leading to expanded momelotinib use and/or development of other targeted therapies for treating anemia in MF and related diseases. [ABSTRACT FROM AUTHOR]