Elritercept Relieves Anemia and Improves Symptoms in Myelofibrosis

Blood Cancers Today (BCT) interviewed Claire Harrison, MD, DM, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK, at the ASH Annual Meeting 2024, held December 7 to 10 in San Diego, California, about updated results from the phase 2 RESTORE trial. This study evaluated the safety and efficacy of elritercept as monotherapy and in combination with ruxolitinib for patients with myelofibrosis (MF) and anemia. The key findings showed that elritercept may help overcome the anemia problem in this population and add to efficacy outcomes.

The phase 2 RESTORE trial (NCT05037760) tested the investigational activin receptor type IIA-Fc fusion protein elritercept for the purpose of restoring effective hematopoiesis, which is a relevant issue in patients with MF. Arm A assessed elritercept as monotherapy, and arm B assessed the agent in combination with the Janus kinase (JAK) inhibitor ruxolitinib in patients with MF and anemia. A prior analysis had demonstrated that thrombocytopenia and diarrhea were the most common treatment-emergent adverse events.¹ Nonetheless, the authors concluded that the agent was generally well tolerated. Moreover, elritercept was associated with improvements in hemoglobin levels, transfusion burden, and platelet counts, indicating that the drug has the potential to target ineffective hematopoiesis, MF, and ruxolitinib-associated cytopenias.¹ Dr. Harrison’s research team additionally observed positive effects with regard to iron homeostasis, inflammation, spleen size, and symptoms of MF. At ASH 2024, updated results of the RESTORE trial were presented.²

BCT talked to Dr. Harrison about the impact elritercept may have on the management of patients with MF.

BCT: With anemia being a critical challenge in MF, how does elritercept aim to improve patient outcomes compared with current JAK inhibitor treatments?

“Anemia is an on-target side effect of JAK inhibitors,” explained Dr. Harrison. “It has been associated with a poor prognosis, increased hospital visits, higher health care costs, and an increased symptom burden for our patients. On the other hand, transfusion independence has been linked to a survival benefit in patients with MF. Elritercept offers an alternative mechanism to target the TGF-β superfamily ligands, complementing the role of JAK inhibitors, acting independently and reducing anemia.” Dr. Harrison emphasized that elritercept has also been linked to reductions in spleen volume, decreased symptoms, and stabilization or improvement of platelet counts. “In the long term, we believe elritercept could improve the bone marrow microenvironment,” she said.

BCT: Could you discuss the significance of the observed hemoglobin improvements in non–transfusion-dependent participants, particularly in arm B with elritercept doses ≥3 mg/kg?

“Hemoglobin improvement has a very significant positive impact on patients and is correlated with symptom improvement,” Dr. Harrison replied. “Anemia is a huge burden for patients with MF, and whilst we would want to see transfusion independence in all patients, we must not forget the impact of a substantial reduction in transfusion requirement and an increment in hemoglobin.”

BCT: Platelet counts were generally stable or increased, even in participants with baseline thrombocytopenia. How might this finding impact treatment safety and tolerability in clinical practice?

“It is a very important finding,” according to Dr. Harrison. “Thrombocytopenia is a well-known unmet need for the MF population. Elritercept was associated with increases in platelet counts, indicating possible improvements in the bone marrow microenvironment. It will lead to the obvious benefit of reducing bleeding but may also allow for optimized dosing of JAK inhibitors. These agents are known to cause thrombocytopenia and when they do, we have to reduce the dose.”

BCT: While reductions in spleen size were less frequent, what potential do you see for elritercept to address splenomegaly in combination with symptom improvements?

“Elritercept has demonstrated the potential to reduce spleen size. I think it’s important to note that we expect to see progressive increases in spleen sizes over time. Therefore, observing stabilization or a modest reduction in many patients is remarkable. Next to this, symptoms consistently improved with elritercept. I expect this to be due to anemia responses and effects of the drug on inflammation.”

BCT: How might the combination of elritercept with ruxolitinib change the treatment landscape for MF, particularly for patients with JAK inhibitor–associated cytopenias?

“Since anemia and thrombocytopenia limit effective dosing of ruxolitinib, the complementary effects of elritercept are highly important to improve therapies for MF,” answered Dr. Harrison. “Furthermore, ruxolitinib does not fully improve splenomegaly or symptoms for patients with MF, even at maximal dose. Elritercept may therefore enhance these outcomes.” There are currently four FDA-approved JAK inhibitors. “I can see a future where elritercept could be combined with any of these agents,” decided Dr. Harrison.

References

1. Harrison C, Chee L, Ross Det al. Elritercept (KER-050) demonstrated potential to treat myelofibrosis and mitigate ruxolitinib-associated cytopenias in the phase 2 RESTORE trial Abstract #S223. Presented at the European Hematology Association Congress; June 13-16, 2024; Madrid, Spain.
2. Harrison C, Chee LCY, Divos T, et al. Hematological improvement and other clinical benefits of elritercept as m, onotherapy and in combination with ruxolitinib in participants with myelofibrosis from the ongoing phase 2 RESTORE trial. Abstract #997. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.