The Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has granted approval for InnoCare Pharma's registrational Phase III clinical trial investigating a novel combination therapy for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The study will evaluate the BCL2 inhibitor ICP-248 (Mesutoclax) in combination with BTK inhibitor orelabrutinib as a first-line treatment option.
Mechanism of Action and Treatment Potential
ICP-248, also known as Mesutoclax, is an orally administered BCL2-selective inhibitor designed to restore normal apoptosis processes in cancer cells. The drug targets BCL2, a crucial regulatory protein in the apoptosis pathway whose abnormal expression is linked to various hematologic malignancies. When combined with orelabrutinib, the fixed-duration treatment aims to achieve deeper remission in treatment-naïve CLL/SLL patients without drug-resistant mutations.
Clinical Development Progress
The advancement to Phase III follows encouraging results from Phase II trials, where the combination demonstrated both promising efficacy and a favorable safety profile in treatment-naïve CLL/SLL patients. This development represents a significant step forward in InnoCare's hemato-oncology portfolio.
Dr. Jasmine Cui, co-founder, chairwoman and CEO of InnoCare, emphasized the strategic importance of this development: "ICP-248 is an important global asset in our hemato-oncology portfolio. We are rapidly advancing multiple clinical trials of ICP-248 globally, including the treatment of non-Hodgkin's lymphoma, and acute myeloid leukemia (AML)."
Disease Burden and Market Context
CLL/SLL represents one of the most common forms of leukemia globally, with approximately 191,000 new CLL cases diagnosed annually and 61,000 related deaths worldwide. The incidence rate in China shows an upward trend, highlighting the growing need for effective treatment options.
Current Treatment Landscape
Orelabrutinib, a key component of this combination therapy, has already established its presence in the market with approvals in China and Singapore. The drug has achieved significant market access in China, with three approved indications included in the National Reimbursement Drug List (NRDL): relapsed/refractory CLL/SLL, relapsed/refractory mantle cell lymphoma (MCL), and relapsed/refractory marginal zone lymphoma (MZL).
The combination of BTK and BCL2 inhibitors represents a promising therapeutic strategy that could potentially deliver improved outcomes for patients with CLL/SLL, marking an important advancement in the treatment landscape for these hematologic malignancies.
