Anemia and Cytopenias Remain Key Unmet Needs in Myelofibrosis

Elritercept (KER-050; TAK-226) is an investigational modified activin receptor type IIA (ActRIIA) ligand trap designed to inhibit activin A and select transforming growth factor-β (TGF-β) superfamily ligands (including activin B and growth differentiation factors 8 and 11), with the goal of improving ineffective hematopoiesis.¹ Dysregulated inflammatory and signaling pathways causing cytopenias, iron dysregulation, and systemic symptoms characterize myelofibrosis (MF), the disease in which this mechanism has been deemed attractive.

Recent clinical studies have shown that pathway targeting not only leads to improvements in hemoglobin (Hgb) and reduction of transfusion burden but also allows the platelet count to be maintained. The latter is an issue of genuine concern in patients who can have their treatment options severely limited by baseline thrombocytopenia.¹

RESTORE Phase 2 Trial Design

RESTORE (NCT05037760) is an ongoing, open-label phase 2 trial assessing elritercept as monotherapy combined with ruxolitinib (Jakafi; Incyte) in adults with MF and anemia. The study enrolled both transfusion-dependent (TD) and non-TD patients with Hgb levels below 10 g/dL.¹ The published Blood abstract reports that Arm A tested elritercept monotherapy and Arm B assessed elritercept added to ruxolitinib.¹ According to the study record, major goals of the study were safety and tolerability assessment and clinical effect characterization on MF signs and symptoms, including anemia-related outcomes, when used with or without the JAK inhibitor.²

Currently, dose selection for further investigation has been centered on subcutaneous administration every 4 weeks, and the report of a recommended phase 2 dose range is 3.75 to 5 mg/kg.¹

Hematologic Improvements: Hemoglobin and Transfusion Burden

In the April 2024 blood report data, the cohort was made up of 23 participants in Arm A and 31 in Arm B, with a median treatment time of 30 weeks across the cohorts. Of those patients, 31% were TD and 59% had thrombocytopenia (platelets <150 10⁹/L) at baseline, representing a very clinically complex population.

Among evaluable non–TD participants, a maximum mean Hgb increase of at least 1.0 g/dL sustained over 12 consecutive weeks (during the first 24 weeks) was observed in 3 of 8 participants in Arm A and 7 of 12 in Arm B; among those receiving at least 3 mg/kg in Arm B, 6 of 10 achieved this Hgb response metric.¹ Notably, Hgb improvements generally coincided with decreases in hepcidin and ferritin, suggesting a potential link between elritercept activity and improvements in iron homeostasis and/or inflammatory signaling.¹

Following transfusion, the results also largely support a positive effect. Within the first 24 weeks, a decrease in 12-week transfusion burden was demonstrated in 3 of 5 TD participants in Arm A and 6 of 10 in Arm B.

In a subgroup with heavier transfusion requirements (3 red blood cell units per 12 weeks at baseline), 10 of 21 participants in Arm B were able to reduce their transfusions by at least 50%, which also included 6 who became transfusion independent; of the group receiving at least 3 mg/kg, 5 of 11 became transfusion independent.¹ Such results have a high clinical impact on patients who otherwise would be subjected to frequent transfusions and iron overload management.

Safety and Practical Considerations for Pharmacy Teams

Elritercept was described as generally well tolerated in the published report, where treatment-emergent adverse events that occurred in at least 15% of participants included thrombocytopenia (19%) and diarrhea (17%).¹ One participant experienced an asymptomatic hemoglobin rise that required dose reduction according to protocol and was considered a dose-limiting toxicity.¹

These preliminary results indicate a number of practical considerations for pharmacists. First, a drug that may improve anemia and reduce the need for transfusions while keeping platelets would significantly help fulfill a long-standing unmet need in MF, especially for patients on ruxolitinib who develop or have worsening cytopenias. Second, like other drugs that affect hematopoiesis, it will be incredibly important to carry out regular blood count monitoring and implement individualized risk mitigation measures, particularly if used in combination with JAK inhibitors that have known warnings of thrombocytopenia, anemia, and neutropenia.³ Lastly, because elritercept is still under investigation, patients must be well informed about the changing data, how to qualify for a trial, and the significance of having a proper safety monitoring system in place.

Conclusion

Takeda has continued to highlight elritercept as a late-stage investigational activin inhibitor under evaluation for anemia associated with hematologic cancers, including MF, with additional oral presentations planned to share updated phase 2 findings.⁴ As RESTORE matures, larger datasets and longer follow-up will be needed to better define durability of response, safety over time, and the extent to which improvements in anemia translate into sustained functional outcomes for patients.

REFERENCES

1. Harrison C, Chee LCY, Devos T, et al. Hematological Improvement and Other Clinical Benefits of Elritercept As Monotherapy and in Combination with Ruxolitinib in Participants with Myelofibrosis from the Ongoing Phase 2 Restore Trial. Blood. 2024;144(Supplement 1):997-997. doi:https://doi.org/10.1182/blood-2024-201729

2. NCT05037760. A study of Elritercept Alone or Together with Ruxolitnib in Adults With Myelofibrosis. Clinicaltrials.gov. Accessed February 5, 2026. https://clinicaltrials.gov/study/NCT05037760

3. Jakafi Prescribing Label. FDA. Accessed February 5, 2026. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202192s015lbl.pdf

4. Takeda unveils pioneering advances in hematologic cancers and rare blood disorders at the 67th American Society of Hematology (ASH) annual meeting. Takeda Oncology. Published November 3, 2025. Accessed February 5, 2026. https://www.takedaoncology.com/newsroom/news-releases/2025/hematologic-cancer-rare-blood/