Approved MPN Treatments & MPN Clinical Trials

The central goal of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms (MPNs) is to develop new and effective therapies for myeloproliferative neoplasms (MPNs) and Systemic Mastocytosis (SM) that will significantly improve the quality of life and the outcomes of our patients, extend survival, and ultimately cure MPNs. The former and present MPN Faculty at the Hanns Pielenz Clinical Research Center for MPNs at UT MD Anderson developed novel MPN medications, such as ruxolitinib and momelotinib, which significantly improved the quality of life and the outcomes of patients with myelofibrosis. On August 28, 2026, rusfertide received regulatory approval for the treatment of patients with polycythemia vera, and on August 31, 2026, ropeginterferon alpha-2b received regulatory approval as a treatment for patients with essential thrombocythemia in the US.

Impact of Approved JAK Inhibitors in the Treatment of Myelofibrosis

Ruxolitinib (JAK1/2 inhibitor) has been a truly transformative medication in the landscape of myeloproliferative neoplasms that dramatically improved the quality of life and extended the survival of patients with myelofibrosis (MF) since its regulatory approval in 2011. Ruxolitinib significantly ameliorates the quality of life of MF patients by substantially improving splenomegaly and the burden of constitutional symptoms, such as fatigue, early satiety, bone pain, low-grade fevers, pruritus, abdominal discomfort, and unintentional weight loss. 

Prior to the clinical development of ruxolitinib, MF treatments were scarce and the quality of life for patients with MF was very poor. Ruxolitinib has become the global standard of care for MF and the backbone of leading novel combination treatments for MF in advanced clinical development. Notably, follow-up analyses of the Phase 3 randomized COMFORT-1 and COMFORT-2 studies documented the marked impact of ruxolitinib versus control in prolonging survival of patients with MF (Verstovsek S. et al., J. Hematol. Oncol. 2017). These findings were confirmed by recent analyses of retrospective and real-world data, for example, the ERNEST study and other studies that were conducted at UT MD Anderson (Verstovsek S, et al., Cancer 2023; Masarova L. et al., Cancer 2023; Verstovsek S. et al., Annals Hematol. 2022; Masarova L. et al., Cancer 2022). Life extension is now recognized as a full-fledged benefit of ruxolitinib.

Ruxolitinib was the first and sole medication that had received regulatory approval for MF until August 16, 2019, when fedratinib was approved as a treatment for MF. Fedratinib, the second approved oral JAK2 inhibitor, may be considered as a good treatment option in second line patients with MF. Fedratinib reduces the spleen size and improves symptoms similarly to ruxolitinib, but fedratinib has a different toxicity profile, requiring a more attentative approach than ruxolitinib. 

Pacritinib (JAK2/IRAK1/ACVR1 inhibitor) was approved as a treatment for MF patients who have severe thrombocytopenia (low platelet counts), on February 28, 2022. In thrombocytopenic patients, treatment with ruxolitinib or fedratinib is not recommended because these agents may exacerbate thrombocytopenia. About 25% of MF patients have moderate to severe thrombocytopenia at diagnosis. Regulatory approval of pacritinib addressed the major unmet need of severely thrombocytopenic patients with MF; these patients had poor prognosis and lacked effective and safe treatment options until pacritinib was approved.

On September 15, 2023, momelotinib received regulatory approval as a treatment for patients who have intermediate- or high- risk MF (primary or secondary MF) and anemia based on the data acquired in the pivotal Phase 3 MOMENTUM trial (NCT04173494) and the data from a cohort of patients who participated in the Phase 3 SIMPLIFY-1 trial (NCT01969838). 

Momelotinib is a unique JAK1/2 inhibitor because it also inhibits ACVR1 and thereby the expression of hepcidin (master regulator or iron in the body) in the liver, leading to marked and sustained anemia benefits, including red blood cell transfusion independence. For a comprehensive review on the mechanism of momelotinib, which improves anemia in patients with MF, please review our article, "Momelotinib: an emerging treatment for myelofibrosis patients with anemia" (Chifotides HT, Bose P, Verstovsek S, J. Hematol. Oncol. 2022).

The regulatory approval of momelotinib was a major advancement in the treatment of anemic patients with MF. Until momelotinib received regulatory approval, there was a critical unmet need for MF patients with anemia, which is one of the hallmarks of the disease. Prior to momelotinib's regulatory approval, Professor Verstovsek, MD, PhD, presented the interview titled, "Momelotinib may become No. #1 choice for second-line therapy in myelofibrosis".

Data from the Phase 3 MOMENTUM trial demonstrated the superior clinical efficacy of momelotinib compared to danazol with respect to anemia measures, and spleen and symptom responses in anemic and symptomatic MF patients. Please review our publication in the leading journal The Lancet (Verstovsek S. et al., 2023) where the final results of the MOMENTUM study were published; our publications on momelotinib's long-term safety and survival benefits in Blood Advances (Verstovsek S. et al., 2023); and our article on momelotinib's efficacy in improving constitutional symptoms in Cancer Medicine (Mesa RA. et al., 2023). The durability of momelotinib's clinical benefits were analyzed in our publication in Lancet Haematology (Gerds AT, Verstovsek S. et al., 2023).

• An expert overview of momelotinib in the treatment of MF can be found in our recent article Bose P. Blood 2024;144(7):708-713.

Please review the UT MD Anderson News Release on the clinical benefits that momelotinib elicited in anemic and symptomatic MF patients in the registrational MOMENTUM clinical trial.

Anemia and especially the need of red blood cell transfusions are considered adverse prognostic factors for disease progression and survival of MF patients. About one third of patients with MF have anemia at diagnosis and approximately half of the patients require red blood cell transfusions one year after diagnosis; eventually, nearly all patients with MF require red blood cell transfusions.

Momelotinib is poised to improve the patients' quality of life by providing significant anemia benefits, including red blood cell transfusion-independence, besides improving splenomegaly and constitutional symptoms. Please review our web page on Current MPN Research and Treatments for an overview of momelotinib’s clinical efficacy in the Phase 3 clinical trials and other novel MPN medications in advanced clinical development. 

The association of the myelofibrosis phenotypes (myeloproliferative and myelodepletive/cytopenic) with clinical manifestations and molecular profiles noted in the patients and the established/emerging treatments were discussed in our comprehensive review was published in Cancers (Basel) 2023, and our review was featured on the cover of Cancers (Volume 15, issue 13; July 2023).

• For a comprehensive overview of the four approved JAK inhibitors (ruxolitinib, fedratinib, pacritinib, momelotinib) and how to select them as treatments for patients with MF, please read our article that was published in Blood, "How I individualize selection of JAK inhibitors for patients with myelofibrosis", Masarova L., Chifotides HT., Blood 2025;145(16):1724-1737.

• Currently, many novel agents (with different biological mechanisms of action) are being evaluated in patients with MF in clinical trials, for example, selinexor, navtemadlin, AJ1-11095, INC033989, nuvisertib, selcodebart, and others. Please review the relevant figure at the top of the page.

Treatments for Polycythemia Vera

For a comprehensive review on PV, please review our article in Nature Reviews Disease Primers (2025) and the relevant visual abstract on PV.

In 2014, ruxolitinib received regulatory approval as a second-line treatment for patients with polycythemia vera (PV) who are intolerant or resistant to hydroxyurea (frontline cytoreductive treatment in PV). The primary goal of PV treatment is mitigation of thrombotic and hemorrhagic events by strictly controlling the hematocrit below 45%. It was demonstrated in two randomized clinical studies that ruxolitinib provided significant clinical benefit in normalizing blood cell counts (red blood cells and platelets), improving constitutional symptoms (e.g., pruritus, splenomegaly, fatigue) and quality of life, and decreasing spleen size. Furthermore, the clinical responses to ruxolitinib in PV patients were durable.

Ropeginterferon alfa-2b is a long-acting interferon that has improved tolerability and reduced dosing frequency (injected subcutaneously once biweekly or less) compared to other interferons, such as pegylated interferon alfa-2a. Ropeginterferon alfa-2b was approved as a front-line treatment for PV patients in the United States in November 2021 and in the European Union in 2019. 

Rusfertide (hepcidin mimetic) is a novel agent that demonstrated remarkable ability to eliminate the need for phlebotomies in the Phase 2 clinical trial REVIVE that was conducted in PV patients who required phlebotomies (NCT04057040). Rusfertide can reduce the overproduction of red blood cells in patients with PV. Excess red blood cells can thicken the blood and increase the risk of cardiovascular complications, for example, stroke, blood clots, and heart attack. The efficacy of rusfertide was also evaluated in PV patients who required frequent phlebotomies (with or without concurrent cytoreductive therapy) to maintain the hematocrit below 45% in the pivotal Phase 3 clinical trial VERIFY (NCT05210790). Rusfertide met the primary and all four key secondary endpoints in the VERIFY trial. The results of the VERIFY trial were published in Blood 2025;146(Suppl.1):81. On August 28, 2026, rusfertide received regulatory approval for the treatment of patients with polycythemia vera in the US, primarily based on the results of the Phase 3 clinical trial VERIFY. 

Treatments for Essential Thrombocythemia

Patients with essential thrombocythemia (ET) were historically treated with cytoreductive agents, such as hydroxyurea, anagrelide, and pegylated interferon, to reduce high platelet counts, which can cause blood clots and bleeding.

Ropeginterferon alpha-2b (long-acting interferon) was evaluated against anagrelide in patients with ET who were resistant or intolerant to hydroxyurea in the randomized Phase 3 clinical trial SURPASS ET trial (NCT04285086). The results of the global study SURPASS ET were published in Mesa R., et al., Masarova L. Lancet Haematology 2025;12(11):e862-875. The phase 2b EXCEED-ET trial (NCT05482971) evaluated ropeginterferon alpha-2b in both treatment-naïve and hydroxyurea pre-treated patients with ET in North America. The results of the clinical trial EXCEED-ET were published in Reeves BN, et al., Masarova L. Lancet Reg. Health Am. 2026. On August 31, 2026, ropeginterferon alpha-2b received regulatory approval as a treatment for patients with essential thrombocythemia in the US based on the results of the pivotal clinical trial SURPASS ET.

INCA033989, a novel first-in-class mutant CALR monoclonal antibody, is currently evaluated in patients with CALR-mutated ET in a Phase 1 clinical trial (UT MD Anderson Protocol #2023-0647). The preliminary results of the study were published in Blood 2025;146(Suppl.1):1024. 

Currently, many promising novel agents (with different biological mechanisms of action) are being evaluated in clinical trials as treatments for PV (for example, DISC-3405, divesiran, sapablursen, AG-236, bomedemstat, givinostat) and ET (for example, INCA033989, INCA035784, JNJ-88549968, bomedenstat).

Perspective and Outlook Regarding Novel Promising Medications in MPNs

Presently, a flurry of other promising new agents are in clinical development for MPNs Please review our web page on Current MPN Research and Treatments  and the figures above for an overview of novel MPN treatments in clinical development. Combination treatments, in which the medications act synergistically (for example, selinexor combined with ruxolitinib), may enhance the depth and duration of spleen and symptom responses of ruxolitinib and improve other aspects of the disease, such as anemia, bone marrow fibrosis, driver mutation burden (for example, JAK2 V617F or CALR), clonal evolution, progression-free survival, and overall survival. Deeper spleen responses (elicited with higher doses of ruxolitinib, for example) and achievement of red blood cell transfusion independence (elicited with momelotinib, for example) have been correlated with increased overall survival in MF patients. Significant efforts are aimed at developing medications that will elicit complete or partial molecular responses, namely elimination or considerable decrease in the burden of driver mutations, such as JAK2 V617F in PV and MF and CALR in MF and ET. The availability of a suite of approved medications for MPNs will allow physicians to tailor and optimize treatments according to the patient’s needs and optimal clinical benefits.