Notice of Initiation of Phase III Study for Chronic Myeloid Leukemia

On August 3, 2022, we made a timely disclosure of “Notice of Initiation of Phase III Study for Chronic Myeloid Leukemia.

This news item is a supplemental explanation of “Chronic Myeloid Leukemia (CML)

Chronic myeloid leukemia (CML) is a disease in which abnormalities in the chromosomes of hematopoietic stem cells cause cancerous leukemia cells to proliferate unlimitedly. Molecular-targeted agent (tyrosine kinase inhibitor, TKI) such as imatinib is used for the management of CML. TKIs kill CML cells, but not the cancer stem cells of CML, resulting in the growth of new CML cancer cells from the cancer stem cells and relapse. The need to continue expensive TKI treatment for a long period of time to cure CML is a major burden on medical economy. Side effects caused by long-term use of TKIs are also a problem, since deaths due to myocardial infarction or cerebral infarction and blindness due to retinal artery occlusion are reported. Therefore, it is important to achieve treatment free remission (TFR) as early as possible.

RS5614 may be a curative agent for CML by releasing CML cancer stem cells from the bone marrow niche and consequently enhancing the therapeutic effect of TKIs. Since the safety and efficacy were confirmed in the late phase II study, we have initiated a phase III study and the first subject has been dosed in the study.

The Phase III study is a multicenter, placebo-controlled, double-blind (*1) study to evaluate the efficacy of RS5614 in combination with TKIs in CML patients, and 60 patients with chronic stage CML who had been treated with TKIs for more than 3 years will be enrolled in the study. The study will verify that the combination of RS5614 plus TKIs significantly increases the DMR maintenance rate (*2) for more than 2 years compared to TKIs alone. This study was selected by the Japan Agency for Medical Research and Development (AMED) as a project in “Practical Research of Innovative Cancer Control” for fiscal 2022, and is being conducted with the support of AMED (Representative organization: Tohoku University, and Renascience is a contributing organization).

The total number of CML patients in Japan is estimated to be more than 15,000, and the number is increasing every year. We would like to deliver this drug to CML patients as soon as possible.

(*1) Double-blind: A clinical trial method in which eligible patients are randomly divided into two groups, one to receive the investigational drug (RS5614) and the other to receive a control drug (placebo with no effect), and both groups receive the drug simultaneously under conditions in which neither physicians nor patients know which drug will be administered. This is a clinical trial method to avoid the possibility of intentionality being reflected in the evaluation: administering an investigational drug to a patient who is expected to respond to the drug, having preconceived notions that the drug should be effective, or affecting patients’ reaction and evaluation to the treatment if they know the drug allocation. The results of each group are compared and evaluated to determine if the investigational drug is effective.

 (*2) DMR maintenance rate: Current treatment of chronic CML requires lifelong use of expensive TKIs, but it has become clear in recent years that some patients who achieve the deepest therapeutic effect, DMR, and maintain it for a certain period do not relapse after TKI discontinuation (TFR). The cumulative DMR achievement rate for one year (48 weeks) published to date for existing TKIs is 8-12% (historical control), but in the late phase II study, the cumulative DMR achievement rate for one year of combination of RS5614 and TKIs was as high as 33%. In other words, the study confirmed the efficacy and the safety of RS5614.