Elritercept Plus Ruxolitinib Demonstrates Favorable Safety and Strong Efficacy for Patients With Myelofibrosis and Anemia: RESTORE Trial
Key Clinical Summary
- Population and Design: Phase 2 RESTORE trial enrolled 38 patients with myelofibrosis and anemia (Hb <10 g/dL), including transfusion-dependent and non-dependent patients (platelets ≥ 25×10⁹/L), to evaluate elritercept—a TGF-β pathway modulator—as monotherapy or in combination with ruxolitinib over 36 weeks.
- Efficacy: At week 36, ~50% achieved transfusion independence ≥ 12 weeks, and > 50% reduced transfusion burden by ≥ 50%; platelet counts increased by > 30×10⁹/L in both low- and high-baseline groups. Symptom improvement occurred in 89%, and spleen volume reduction in 20 to 22% of patients.
- Safety: The regimen was well tolerated, with mostly grade 1–2 gastrointestinal AEs (notably diarrhea) and few grade ≥ 3 events.
- Clinical Relevance: Elritercept + ruxolitinib demonstrated clinically meaningful improvements in anemia, platelet count, and symptom burden with an acceptable safety profile, supporting advancement to a phase 3 trial for broader evaluation in myelofibrosis.
Ciro Rinaldi, MD, PhD, University of Lincoln, Lincoln, England, presented results from the phase 2 RESTORE trial, evaluating the combination of elritercept and ruxolitinib among anemic patients with myelofibrosis (MF) who were either resistant or intolerant to ruxolitinib alone at the 2025 ASH Annual Meeting & Exposition.
After 36 weeks, more than 50% of patients achieved transfusion independence, with significant improvements in platelet counts, symptom burden, and spleen volume. The regimen was well tolerated, with mostly mild gastrointestinal side effects.
Dr Rinaldi concluded, “It is clearly an interesting combination to follow. I think there is quite a lot there to go for a phase 3 where we can potentially look at a benefit for a wider population.”
Transcript:
My name is Ciro Rinaldi. I'm a hematologist from England. I work for a trust called United Lincolnshire Teaching Hospitals and I'm professor of hematology at University of Lincoln in England. I'm here at ASH to present the results of a phase 2 clinical trial, RESTORE, which combined 2 drugs, elritercept and ruxolitinib in patients with myelofibrosis.
The population of patients selected were anemic myelofibrotic patients with a hemoglobin level less than 10. They could have been either transfusion dependent or transfusion non-dependent with or without thrombocytopenia, with a platelet count or more equal to 25 with or without transfusion. Elritercept is active in analog, block downstream protein of TGF-β. TGF-β, this regulation has been involved in arresting hematopoiesis in myelofibrosis model, is involved in fibrosis. Preclinical data using a compound called ARC050, which was the anticipator of elritercept, reverse some of those dysfunctions and also reverse some of the toxicity related to ruxolitinib treated mice models.
The trial was designed for either patients intolerant or resistant to ruxolitinib, where elritercept was used as a monotherapy, or in patients that were exposed to ruxolitinib on a stable dose for at least 4 weeks prior to treatment and at least 8 weeks of treatment with ruxolitinib along in combination with elritercept.
What we presented here at ASH, is the final data on 38 patients following 36 weeks assessment. What we found was a significant improvement in transfusion requirement. Approximately more than 49, 50% of patients at week 36 of assessment achieved transfusion independence for longer than 12 weeks. They also continued for 16 and 24 weeks in a large proportion of patients. More than 50% of patients reduced by 50% transfusion burden, which is great data in this group of patients. It was also a very good response in platelets. Patients’ population could be either more than 150 platelets recruitment or less than 150 platelets. They both responded with an increment in platelet count of more than 30 units or more, which again, is a very good results considering this group of patients.
There was a good response in terms of symptom burden. Probably more than 89% of patients achieved some TSS improvement. Again, considering that majority of people recruited in the study were already exposed to ruxolitinib, having an additional improvement in symptoms is really good. Also, in terms of spleen reduction, approximately 20, 22% of patients had a further reduction in spleen volume following 24- and 36-weeks exposure to the drug. The drug is well-tolerated. The combination was well tolerated. Very few grade 3 or more side effects. Majority of the side effect were grade 1 and 2, mainly gastrointestinal symptoms, particularly diarrhea, which was manageable and it was non-persistent.
In conclusion, the drug seems to be very well-tolerated by patients when given in addition to ruxolitinib, it clearly improved the transfusion burden and the anemia in these patients, and it also has an impact on spleen volume reduction and symptom burden. It is clearly an interesting combination to follow. I think there is quite a lot there to go for a phase 3 where we can potentially look at a benefit for a wider population.
Source:
Rinaldi C, Ross D, Chee L, et al. Hematological and clinical improvements with elritercept (KER-050, TAK-226) at the recommended Phase 2 dose (RP2D) in patients with myelofibrosis (MF) receiving ruxolitinib: Updated results from the Phase 2 restore trial. Dec 6-9, 2025; Orlando, FL. Abstract: 909
