Ryvu Therapeutics has announced the dosing of the first patient in the REMARK Phase II clinical trial, evaluating RVU120 as a monotherapy for the treatment of anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS). The REMARK study (NCT06243458) is an open-label, multicenter trial conducted through the European Myelodysplastic Neoplasms Cooperative Group (EMSCO) network. It aims to assess the safety and efficacy of RVU120 in patients with LR-MDS who have limited treatment options.
The trial has received approval from regulatory bodies and ethics committees in Germany, Spain, Poland, Italy, and France, operating under the European Union Clinical Trial Regulation (EU-CTR) 2023-509947-29. The study plans to enroll approximately 40 patients across up to 25 clinical sites worldwide.
RVU120: Targeting Anemia in LR-MDS
RVU120 is a novel small-molecule cyclin-dependent kinase (CDK) 8/19 inhibitor. The REMARK trial is specifically designed to evaluate its potential in treating anemia associated with LR-MDS. Patients enrolled in the study will receive RVU120 for a minimum of eight cycles (24 weeks).
The primary endpoint of the REMARK study is to achieve hematologic improvement, specifically an erythroid response (HI-E). Secondary endpoints include red blood cell (RBC) transfusion independence, improvements in hemoglobin levels, enhanced quality of life, assessment of disease progression, and analysis of specific gene mutations.
Expert Perspectives
"We are glad to announce the initiation of the REMARK study for RVU120, which can potentially help patients with lower-risk MDS," said Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics. "This study builds upon the promising results from our Phase Ib study in patients with AML and high-risk MDS, where we observed hematologic improvement in several patients, including cases of transfusion independence. The objective is to further assess the safety and efficacy of RVU120 in patients with lower-risk MDS, underpinned by robust preclinical and mechanistic evidence."
Prof. Uwe Platzbecker, M.D., Director of the Clinic and Poliklinik for Hematology, Cell Therapy and Hemostaseology at the Leipzig University Hospital and Coordinating Principal Investigator, added, "RVU120 has shown promising hematologic improvement in patients with off-hematologic impaired bone marrow function. I am optimistic that this clinical evidence will translate into a positive outcome of the REMARK study... It may aid in achieving our ultimate aim to alleviate the need for red blood cell transfusions in these patients."
Mechanism of Action and Rationale
The REMARK study is based on existing clinical safety and efficacy data, along with preclinical and mechanistic evidence. The pathogenesis of MDS involves gene expression alterations that impede the maturation of hematopoietic cells. RVU120 is designed to trigger erythroid gene expression programs, orchestrated by STAT5 and GATA1, in aberrant stem cells from MDS patients. Ryvu Therapeutics emphasizes that RVU120's activity does not lead to significant toxicity in the hematopoietic system, positioning it as a promising candidate for transfusion-dependent MDS patients.
Broader Clinical Program
REMARK is the third of four planned Phase II clinical studies of RVU120 scheduled for launch in 2024. Ryvu has already initiated patient treatment in the RIVER-52 and RIVER-81 studies in AML. The POTAMI-61 study, which will evaluate RVU120 as a monotherapy and in combination therapy for myelofibrosis (MF), is expected to begin shortly.
