Category Archives: Research

Takeda Receives U.S. FDA Approval of MIMRYLO™ (rusfertide), Marking a Potential Shift in the Treatment Paradigm for Polycythemia Vera

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August 28, 2026

  • MIMRYLO, a First-in-Class Medicine with a Unique Mechanism of Action, is Approved for the Treatment of Erythrocytosis in Adults with Polycythemia Vera (PV)
  • MIMRYLO Has Been Shown to Maintain Hematocrit Control, the Primary Treatment Goal in PV, as Well as Reduce Phlebotomy Burden and Improve Fatigue
  • Approval Supported by Phase 3 VERIFY Results Showing 76.9% of Patients Achieved Clinical Response During Weeks 20-32

OSAKA, Japan and CAMBRIDGE, Massachusetts, August 28, 2026 – Takeda (TSE:4502/NYSE:TAK) announced U.S. Food and Drug Administration (FDA) approval of the New Drug Application (NDA)* for MIMRYLO™ (rusfertide) for the treatment of erythrocytosis in adults with polycythemia vera (PV), a blood cancer.

MIMRYLO is a first-in-class hepcidin mimetic designed to regulate iron distribution in the body and red blood cell overproduction to control hematocrit levels, which is the ratio of red blood cells to the total amount of blood in the body. Maintaining controlled hematocrit levels below 45% is the primary treatment goal in PV.1

“For patients living with PV, uncontrolled hematocrit can have serious consequences, including an elevated risk of life-threatening thrombotic events,” said Andrew T. Kuykendall, M.D., VERIFY lead investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. “Current treatments, such as phlebotomy, leave a significant gap for too many patients and can pose challenges to daily life and routines. The approval of MIMRYLO offers clinicians and patients a novel, first-in-class therapy that targets erythrocytosis, which drives excess red blood cell production in PV. The strength and consistency of the VERIFY data give me real confidence in MIMRYLO’s potential to advance how we treat PV in everyday practice and to maintain hematocrit control.”

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Ipsen completes acquisition of Kartos Therapeutics, strengthening late-stage Oncology pipeline

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Ipsen (Euronext: IPN; ADR: IPSEY) announced today it has completed the acquisition of Kartos Therapeutics, a clinical-stage biopharmaceutical company adding late-stage MDM2 inhibitor navtemadlin in Phase III clinical development in myelofibrosis.

About navtemadlin
Navtemadlin is an investigational oral MDM2 inhibitor being developed as an add-on therapy to ruxolitinib for patients with myelofibrosis who have a suboptimal response to ruxolitinib. The Phase III POIESIS study is evaluating whether the addition of navtemadlin could improve clinical outcomes compared with ruxolitinib alone in this patient population. Early clinical data demonstrate navtemadlin has the potential to transform suboptimal responses to standard of care ruxolitinib into clinically meaningful responses in patients with intermediate and high risk TP53wt myelofibrosis, to provide both enhanced clinical outcomes and potential disease-modifying benefit.

About myelofibrosis
Myelofibrosis is a myeloproliferative neoplasm, frequently linked to alterations in the JAK/STAT pathway, in which patients develop bone marrow fibrosis due to the abnormal proliferation of hematopoietic stem cells and secretion of fibrogenic cytokines. As marrow function declines, blood production shifts to other organs, most often the spleen, leading to splenomegaly. Myelofibrosis is characterized by bone marrow failure, fibrosis, splenomegaly and a high symptom burden that can significantly affect quality of life, including fatigue, night sweats and other progressive symptoms. It also carries a risk of transformation to acute myeloid leukemia. The median age at diagnosis is approximately 67–69 years and the condition affects around 1.5 per 100,000 people in the U.S. and Europe. Approximately 75–89% of patients are intermediate- or high-risk at diagnosis and more than 95% are TP53wt. Ruxolitinib, a JAK inhibitor, is the first-line standard of care; however, it is estimated that a significant proportion of patients have an initial suboptimal response and approximately 50%-75% discontinue treatment after three years. Median overall survival is typically one to two years after treatment discontinuation, underscoring the need for new strategies that can increase the number of patients that can achieve optimal clinical outcomes.

About Ipsen
We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fueled by internal and external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries.

Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com.

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Engulfment Reduces Patient Quality of Life in MPNs

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Jonathan Goodman, MPhil
Publish Date

Engulfment is a major factor affecting patient quality of life (QoL) among individuals diagnosed with myeloproliferative neoplasms (MPNs), according to research published in the European Journal of Oncology Nursing.

Psychological guidance aiming to mitigate the feeling of being overwhelmed by disease — the notion of engulfment in clinical medicine — is essential for improving QoL, the authors noted.

Although it is recognized that MPNs can drastically and negatively affect patient QoL, there is little understanding of the ways this occurs. For this longitudinal study, researchers evaluated psychosocial adjustment to living with MPNs, including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), with a focus on 4 factors: problem-solving coping, self-management, illness identity, and resilience.

Overall, 338 patients were enrolled. The researchers evaluated measurements of the 4 key factors at baseline and 6 months thereafter using established questionnaires, including the EORTC-QLQ-C30 for QoL measurements.

At enrolment, the average age was 62.8 years, the time since diagnosis was 7.7 years, and 63.6% of patients were female sex; 38.2%, 45.3%, and 16.6% of patients had been diagnosed with ET, PV, and MF, respectively.

The findings of this study indicate that psychosocial adjustment is important for QoL in patients with MPN, especially when adjustment is not optimal.

Analysis of the collected data suggested that II-subscale engulfment most strongly and negatively affected patient QoL (beta, 0.37; P <.001); this variable remained significant after the inclusion of control variables in the model, though the signal was less pronounced (beta, 0.16; P < .05).

Moreover, baseline QoL (beta, 0.32, P <.001) a wait-and-see treatment option (beta, 0.11, P <.05), and symptom burden at the second timepoint (beta, 0.36, P < .001) were all predictive of QoL.

“The findings of this study indicate that psychosocial adjustment is important for QoL in patients with MPN, especially when adjustment is not optimal,” the study authors wrote in their report. “Furthermore, the impact of MPN symptoms on QoL should not be underestimated.”

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Defective neutrophil clearance in JAK2V617F myeloproliferative neoplasms drives myelofibrosis via immune checkpoint CD24

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May 15, 2025

Eman Khatib-Massalha, Christian Andrea Di Buduo, Agathe L Chédeville, Ya-Hsuan Ho,…Simón Méndez-Ferrer Corresponding Author
Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell-driven malignancies marked by excessive myelopoiesis and high risk of myelofibrosis, which remains therapeutically challenging. Senescent neutrophils home daily to the bone marrow (BM) to be cleared by macrophages. This avoids their accumulation, which can increase the risk of chronic inflammation or oncogenesis. Neutrophils carrying the most common oncogenic MPN driver (JAK2V617F) are protected from apoptosis, which may prolong their lifespan and enhance their pro-inflammatory activity. On the other hand, abnormal interactions of neutrophils with megakaryocytes (“emperipolesis”) have been associated with BM fibrosis in disparate hematological disorders, including MPN and grey platelet syndrome; however, the underlying pathophysiology remains unclear. We investigated neutrophil homeostasis and cellular interactions in MPN. We found that senescent neutrophils evade homeostatic clearance and accumulate in JAK2V617F MPN, but not in MPN caused by the second most prevalent mutations affecting Calreticulin (CALR) gene. This is explained by GM-CSF-JAK2-STAT5-dependent upregulation of the “don’t-eat-me” signal CD24 in neutrophils. Mechanistically, JAK2V617F CD24hi neutrophils evade efferocytosis, invade megakaryocytes and increase active TGF-b. Collectively, JAK2V617F neutrophil-megakaryocyte interactions promote platelet production in a humanized bioreactor and myelofibrosis in mouse models. Notably, chronic antibody blockade or genetic loss of CD24 restores clearance of senescent neutrophils, reduces emperipolesis and active TGF-b. Consequently, CD24 blockade improves thrombocytosis and prevents myelofibrosis in MPN mice. Taken together, these findings reveals defective neutrophil clearance as a cause of pathogenic microenvironmental interactions of inflammatory neutrophils with megakaryocytes, associated with myelofibrosis in MPN. Our study postulate CD24 as a candidate innate immune checkpoint in MPN.

The evolving landscape of epigenetic target molecules and therapies in myeloid cancers: focus on acute myeloid leukemia and myeloproliferative neoplasms

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Published May 15, 2025

Michael W. M. Kühn, Naveen Pemmaraju & Florian H. Heidel

Abstract

Research on myeloid neoplasms, a field that has been driving scientific advances in cancer for over 50 years, has yielded many discoveries that have fundamentally reshaped our understanding of cancer biology. These insights, often the product of leukemia research, have been instrumental in developing more mechanism-based treatments in the early 2000s [1]. Recognizing epigenetic dysregulation as a common disease mechanism in myeloid cancers has been groundbreaking regarding recent treatment developments that exploit chromatin-based oncogenic mechanisms. In the case of acute myeloid leukemia (AML), sequencing studies aimed at assessing the complement of genetic alterations demonstrated that more than 60% of AML cases harbored disease-driving mutations in epigenetic regulators. This high prevalence underscores the importance of epigenetic dysregulation in AML pathogenesis [2, 3]. Chromatin regulators commonly control disease-specific transcriptional programs, making them attractive therapeutic targets to manipulate neoplastic gene expression programs, particularly in myeloid neoplasms. Several drugs targeting epigenetic mechanisms and exploiting myeloid disease-specific dependencies have recently been approved for treating myeloid neoplasms. Many additional drugs are currently being investigated in clinical trials, and numerous new compound developments are being studied in preclinical studies. This manuscript will review (1) chromatin-based disease mechanisms, such as DNA methylation, chromatin regulatory complexes, and histone modifications, currently investigated for therapeutic exploitation in myeloid malignancies, and (2) therapeutic developments already approved or investigated for treating these diseases.

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Management of common autoimmune diseases in patients with myeloproliferative neoplasms treated with pegylated interferon alfa—case report, review of the literature and multidisciplinary clinical practice recommendations

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May 8, 2025

Axel Rüfer, Christoph Brand, […], and Sacha S. Zeerleder

Abstract

Pegylated interferons alfa are increasingly used in patients with myeloproliferative neoplasms (MPN) due to their potential disease-modifying effect. Ropeginterferon alfa-2b has been approved for patients with polycythemia vera (PV) with no symptomatic splenomegaly as first-line cytoreductive therapy, based on the results of the PROUD-PV/CONTINUATION-PV studies, documenting significantly higher rates of complete hematologic response (CHR) compared with hydroxyurea from 2-year timepoint onward. Although safety profile of pegylated interferons is overall good, interferon-related toxicities can occur. Focus of this article is on interferon-mediated autoimmune diseases. We describe two patients with PV treated with pegylated interferons alfa, one patient developed a cutaneous, paranasal sarcoidosis without any systemic symptoms and was successfully treated with topical steroids. The other patient developed widespread psoriatric skin lesions, which were treated with moderate effect with topical therapy with calcipotriene and betamethasone dipropionate foam, antidry calm lotion and in the course of the disease with ultraviolet light therapy (UVB). Only with methotrexate she achieved a nearly complete remission of the psoriasis. In both patients pegylated interferon was continued in view of the CHR and therefore the beneficial effect on MPN. We review the pertinent literature on the management of interferon-mediated autoimmune diseases in patients with MPN. As there is little published evidence on that topic, we propose multidisciplinary clinical practice recommendations based on available evidence and clinical experience in the management of patients with MPN treated with pegylated interferon alfa.

National Health Expenditure Associated With Myeloid Neoplasms Survival in Europe

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Andrea S. Blevins Primeau, PhD, MBA
Publish Date

An analysis of the EUROCARE found that lower total national health expenditure (TNHE) was associated with shorter survival among patients with some types of myeloid neoplasms (MNs), according to a report published in the European Journal of Oncology.

The researchers also reported that 10-year relative excess risk of death (RER) was generally higher for patients in regions with lower TNHE.

EUROCARE-6 is a dataset in the EUROCARE study that is derived from 27 European countries of patients aged 15 or older diagnosed with an MN between 2001 and 2013. MNs included acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and myelodysplastic syndrome (MDS).

There were a total of 267,968 MN cases in the dataset, of which, 41.1% were AML, 32.2% were MPNs, 11.7% were CML, 6.8% were PV, 7.4% were ET, and 19.6% were MDS, and 4.4% were MDS/MPN.

Countries in the lowest TNHE quartile included Bulgaria, Croatia, Estonia, Latvia, Lithuania, Poland, and Slovakia. Countries in the highest TNHE quartile included Austria, Denmark, Germany, Norway, and Switzerland. The median follow-up was 13 years.

At 10 years, the age-standardized relative survival (ASRS) ranged from 61.2% for MPNs to 15.6% for AML. Within MPNs, the 10-year ASRS was 75.2% for ET, 70.9% for PV, and 52.5% for CML.

Countries in the lowest TNHE quartile demonstrated lower 10-year ASRS rates compared with countries in the highest quartile for AML, MPN, and MDS.

A similar trend was observed for 10-year RERs for most MNs, with higher RERs associated with lower TNHE quartile. For example, the lowest TNHE quartile was significantly associated with a greater 10-year RER for MPN (RER, 1.32; 95% CI, 1.30-1.35), AML (RER, 1.28; 95% CI, 1.25-1.31), and acute promyelocytic leukemia (RER, 1.42; 95% CI, 1.12-1.80).

The highest quartile was significantly associated with lower 10-year RER for MPN (RER, 0.80; 95% CI, 0.78-0.81) and AML (0.86; 95% CI, 0.84-0.88), but not some subtypes of AML and APL.

“TNHE is associated with geographical inequalities in MN prognosis,” the researchers concluded in their report. “Policy decisions on allocating economic resources are needed to reduce these differences.”

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Prediction of resistance to hydroxyurea therapy in patients with polycythemia vera: a machine learning study (PV-AIM) validated in a prospective interventional phase IV trial (HU-F-AIM)

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Published April 25, 2025

Florian H. Heidel, Valerio De Stefano, Matthias Zaiss, Jens Kisro, Eva Gückel, Susanne Großer, Mike W. Zuurman, Kirsi Manz, Kenneth Bryan, Armita Afsharinejad, Martin Griesshammer & Jean-Jacques Kiladjian

Abstract

Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thromboembolic (TE) risk and hematologic complications. Hydroxyurea (HU) serves as the most frequently used first-line cytoreductive therapy worldwide; however, resistance to HU (HU-RES) develops in a significant subset of patients, leading to increased morbidity and necessitating alternative treatments. This study, part of the PV-AIM project, employed machine learning techniques on real-world evidence (RWE) from the Optum® EHR database containing 82.960 PV patients to identify baseline predictors of HU-RES within the first 6–9 months of therapy. Using a Random Forest model, the study analyzed data from 1850 patients, focusing on laboratory parameters and clinical characteristics. Key predictive markers included red cell distribution width (RDW) and hemoglobin (HGB), showing the strongest association with HU-RES. A synergistic interaction between RDW and HGB was identified, enabling TE risk stratification. This study provides a robust framework for early detection of HU-RES using readily available clinical data, facilitating timely intervention. These findings underscore the importance of personalized treatment approaches in managing PV and highlight the utility of machine learning in enhancing predictive accuracy and clinical outcomes. Based on the results of PV-AIM we initiated an open-label, prospective, single-arm, interventional, phase IV study (HU-F-AIM) evaluating HU-resistance/intolerance. Validation of predictive biomarkers may facilitate identification of patients at risk of HU resistance who may benefit from alternative treatment options, possibly preventing ongoing phlebotomy during HU treatment, a frequent therapeutic choice in high-risk PV associated with early disease progression and increased thromboembolic complications. We propose an updated terminology that differentiates between true molecular resistance and clinical resistance, that may indicate the requirement for alternative therapeutic strategies.

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Diagnosis and Management of PV and ET in Pediatric Populations Needs Improvement

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Caleb Rans, PharmD
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Polycythemia vera (PV) and essential thrombocythemia (ET) are rarely diagnosed in children, adolescents, and young adults. As the median age at diagnosis for these conditions is usually over 60 years, few pediatricians are familiar with their clinical, biological, and genetic features.1-3 Early diagnosis is essential to assess the need for specialized treatments and to prevent long-term complications, such as hemorrhage, thrombosis, or progression to secondary malignancies.1

In a 2-part study published in the European Journal of Pediatrics, Agathe Picard, MD, of the department of pediatric oncohematology at the Rennes University Hospital in France, and colleagues, analyzed practices around the diagnosis and management of pediatric patients with PV and ET in France.

Methodology and Study Design

In the first part of the study, a national practice survey about pediatric patients diagnosed with PV or ET was performed. The 8-question survey was sent to all pediatrician members of the leukemia committee of Société Française de lutte contre les Cancers et leucémies de l’Enfant et de l’adolescent (SFCE), and all hematologist members of France Intergroupe des Syndromes Myéloprolifératifs (FIM).

AYA [patients] should be referred to specialized units that consider the social, psychological, and educational needs of these patients.

In the second part, a retrospective cohort study was conducted at 7 pediatric oncohematology departments in western France. The researchers analyzed clinical, biological, and genetic data, as well as treatment and complication patterns from 17 pediatric patients with PV or ET, all of whom were diagnosed before the age of 18.

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Protein Disulfide Isomerase Could Be Therapeutic Target for MF

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Özge Özkaya, MSc, PhD
Publish Date

Protein disulfide isomerase may be involved in the underlying pathogenesis of thrombotic events in Philadelphia-negative myeloproliferative neoplasms such as myelofibrosis (MF), according to a new study published in the Egyptian Journal of Internal Medicine.

It could also be valuable in predicting the risk of developing thromboembolic events, the researchers noted.

These findings suggest that protein disulfide isomerase could be used as a therapeutic target to prevent thrombotic events in patients with MF and other myeloproliferative neoplasms.

For the study, a team of researchers, led by Mai Galal Elshenoufy, MD, PhD, from Cairo University in Egypt, measured the levels of protein disulfide isomerase in the serum of patients with myeloproliferative neoplasms and assessed its role as a possible marker of increased risk of thromboembolic events.

They found that the levels of the enzyme were pathologically high in the serum of patients with myeloproliferative neoplasms compared to controls. The levels were also higher in patients with arterial thrombosis, but this finding had no statistical significance.

Future work should evaluate the levels of protein disulfide isomerase in a larger group of patients with myeloproliferative neoplasm with and without thrombotic events, and in patients with arterial versus venous thrombosis, they said.

Finally, measuring the levels of protein disulfide isomerase before and after aspirin therapy could give clues about the effect of this treatment, they added.

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