Abstract
Myelodysplastic neoplasms (MDS) are characterized by ineffective hematopoiesis and multiple cytopenias and result in adverse outcomes, including reduced life expectancy. An unmet need remains for efficacious new treatments for anemia in patients with lower-risk MDS that improve quality of life and outcomes, particularly in patients with ring sideroblast (RS)-negative disease or those with a high transfusion burden (HTB). Elritercept is an investigational, modified activin receptor type 2A/IgG1 fusion protein designed to bind and block downstream signaling of select transforming growth factor-β superfamily ligands. Elritercept is being evaluated in diseases with ineffective hematopoiesis, including MDS (NCT04419649) and myelofibrosis (NCT05037760). In preclinical studies, elritercept demonstrated potential to provide robust, sustained hematological improvement in patients with MDS, including those with HTB and/or non-RS MDS.
RENEW (NCT06499285) is a global, multicenter, randomized, double-blind, placebo-controlled phase 3 study evaluating the efficacy and safety of elritercept in adults with transfusion-dependent, very low- low- and intermediate-risk MDS (lower-risk MDS) per revised international prognostic scoring system. Eligible participants are ≥18 years old and have MDS with/without RS and low transfusion burden (LTB, 4 to 7 red blood cell units per 16 weeks) or HTB (≥8 units per 16 weeks). Approximately 225 participants will be randomized 2:1 to receive elritercept 3.75 mg/kg subcutaneously every 4 weeks (with up-titration to 5 mg/kg after ≥8 weeks) or placebo. Participants will be stratified as RS-positive/non-RS and baseline LTB/HTB. A double-blind treatment period consisting of a primary phase (24 weeks) will precede a secondary phase (24 weeks) and extension phase (until end of treatment). Participants will then undergo an 8-week safety follow-up and long-term follow-up. Every quarter during long-term follow-up, data will be collected on survival, first dose of the next MDS treatment line, and progression to acute myeloid leukemia, if applicable. The primary endpoint is the proportion of participants achieving transfusion independence (TI) ≥8 weeks from baseline through week 24. The secondary endpoints are the proportion of participants achieving TI ≥24 weeks from baseline through week 48, the proportion with HTB achieving TI for ≥8 weeks from baseline through week 24, and the incidence and severity of adverse events and serious adverse events.