Development status

Therapeutic for chronic myeloid leukemia (CML)


Chronic myeloid leukemia (CML) is caused by an abnormality in the chromosomes of hematopoietic stem cells, which leads to the unrestricted growth of cancerous leukemia cells.

The mainstream treatment for CML is tyrosine kinase inhibitor TKIs (such as imatinib), but TKIs do not cure CML because they do not act on cancer stem cells that hide in what is called the bone marrow niche, and CML relapses when TKIs are withdrawn.

It is now clear that PAI-1 inhibitors act on cancer stem cells and enhance the effect of TKIs, resulting in the cure of CML. In fact, when this PAI-1 inhibitor was combined with TKIs in a mouse model of CML, the number of cancer stem cells remaining in the bone marrow was markedly reduced and the survival rate was greatly improved compared to the administration of TKIs alone.

Phase IIb Study

TKIs were combined with PAI-1 inhibitors in patients with chronic-phase CML. The cumulative achievement rate of deep molecular remission (DMR) at 48 weeks after the start of treatment was compared with the historical control 8% (effect of TKIs alone). 11 out of 33 patients achieved DMR, 33.3% (Proof-of-Concept obtained). As for safety, there were no serious adverse events causally related to the study drug.

A double-blind, placebo-controlled Phase III trial to evaluate the efficacy of RS5614 in combination with TKI in patients with chronic phase CML is being prepared.

Phase III Study

Based on the results of the Phase IIb Study, the Pharmaceuticals and Medical Devices Agency (PMDA) provided the advice for Phase III Study in face-to-face meetings, and the study protocol of a placebo-controlled, double-blind Phase III clinical trial was established to evaluate the efficacy of the combination of TKI and RS5614 in patients with chronic phase CML. This clinical trial will be conducted as an investigator-initiated clinical trial starting in fiscal 2022.