The RESTORE trial: elritercept alone or in combination with ruxolitinib for the treatment of myelofibrosis

During EHA 2025, Prof Timothy Devos (University Hospitals Leuven, Leuven, Belgium) presented results of the ongoing, phase II RESTORE trial in which the activin receptor type IIA ligand trap elritercept is being evaluated in the treatment of myelofibrosis. Elritercept is specifically designed to inhibit activin A and select TGF-β superfamily ligands (activin B, GDFs 8&11) to improve hematopoiesis.

The phase II RESTORE study is evaluating the safety and efficacy of elritercept either (Arm A) alone or in combination with ruxolitinib (Arm B) in MF patients with anemia. At baseline, 70% of the 29 study participants received ≥3 red blood cell units per 12 weeks, 63% had thrombocytopenia (<150 x10⁹/L), 63% had splenomegaly (volume ≥450cm³) and 73% had a total symptom score (TSS) of 10 or more at baseline. Elritercept was generally well tolerated both as monotherapy and in combination with ruxolitinib. 

Overall, 52% of evaluable non-transfusion dependent patients in both arms experienced a maximum mean increase in hemoglobin (Hb) of 1.0g/dL or more for 12 weeks during the first 24 weeks. In Arms A and B, platelet counts were generally stable or improved, including in participants with baseline thrombocytopenia. Over 24 weeks, 24% of patients in the study achieved transfusion independence (TI). In Arm B, 63% of the transfusion dependent patients experienced a ≥50% reduction in their transfusion need and 38% became transfusion independent. A spleen volume reduction (SVR) of 10% or more was observed in 40% of the patients in the study at week 24 (15% SVR ≥35%). In the combination arm (Arm B), 50% achieved a SVR ≥10% and a quarter of patients achieved a SVR ≥35% by week 24. At week 24, a reduction in TSS was observed in 67% of evaluable participants in Arms A and B with 5 participants achieving an improvement of 50% or more.

In conclusion, elritercept was generally well-tolerated and showed the potential to treat different disease aspects of myelofibrosis. As such, these findings support the ongoing evaluation of elritercept (alone or in combination with ruxolitinib) in the treatment of myelofibrosis.