Ciro Rinaldi, MD, Consultant Hematologist and Professor of Hematology at United Lincolnshire Hospital, discusses treatment with elritercept for patients with myelofibrosis (MF).
MF is characterized by the buildup of scar tissue in the bone marrow. The bone marrow contains stem cells that will produce blood cells, but because of the fibrosis, the bone marrow is unable to make enough normal blood cells. This may lead to anemia, weakness, fatigue, and swelling of the liver and spleen. The disorder occurs when blood stem cells develop somatic genetic changes in the JAK2, MPL, CALR, and TET2 genes. Other genes may also be involved.
Elritercept is an investigational, modified activin receptor type IIA/IgG1 fusion protein designed to selectively bind and block downstream signaling of transforming growth factor-β (TGF-β) superfamily ligands, including activin A, activin B, growth differentiation factor 8 (GDF8), and GDF11. By blocking the signaling of these ligands, elritercept aims to restore functional hematopoiesis.
Recently, data from the ongoing open-label phase 2 RESTORE clinical trial (NCT05037760) was presented at the American Society of Hematology (ASH) 2025 meeting. This study evaluated the safety, tolerability, pharmacokinetics, and efficacy of elritercept as monotherapy (arm A) or in combination with ruxolitinib (arm B) in patients with MF and anemia or non-transfusion dependent. Data was presented on 38 patients in arm B who received elritercept starting at the recommended phase 2 dose (RP2D) of 3.75 mg/kg in combination with ruxolitinib.
The median duration of elritercept add-on treatment was 34 weeks. By week 24, among transfusion-dependent patients with at least 12 weeks of hemoglobin/red blood cell (RBC) transfusion recorded, 30.4% achieved RBC transfusion independence, 17.4% achieved transfusion independence with a concurrent mean hemoglobin increase of 1.5 g/dL or greater, and 56.5% experienced a 50% or greater reduction in RBC transfusions from baseline over any consecutive 12 week period.
In non-transfusion dependent patients, 38.5% achieved a mean hemoglobin increase of 1.5 g/dL or greater over any 12 week period.
In the combined group of transfusion dependent and non-transfusion dependent patients with an evaluable assessment at week 24, 14.3% achieved spleen volume reduction of 25% or greater, 19% achieved a 50% or greater reduction in MF Symptom Assessment Form Total Symptom Score, and 36% experienced improvements of 5 points or more in PROMIS Fatigue T score.
Additionally, 36.8% of patients achieved a mean platelet increase of 30 x 10 to the ninth power/L or greater over any consecutive 12 week period within the first 24 weeks. JAK2 V617F variant allele frequency reduction of 50% or greater was observed in 3 of 18 evaluable patients at week 24, with sustained reductions observed at week 52. For the remainder of patients with available data, the variant allele frequency remained unchanged at weeks 24 and 52 with further follow-up ongoing.
The most common adverse events were diarrhea and thrombocytopenia. No patients discontinued elritercept due to an adverse event.
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To learn more about MF and other rare cancers, visit https://checkrare.com/diseases/cancers/