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December 11, 2012

Results of a Phase 2 Clinical Trial on Mogamulizumab (KW-0761) to Treat Peripheral T-Cell Lymphoma (PTCL) and Cutaneous T-Cell Lymphoma (CTCL) in Japan

Tokyo, Japan, December 11, 2012 --- Kyowa Hakko Kirin Co., Ltd. (Tokyo: 4151, President and CEO: Nobuo Hanai, "Kyowa Hakko Kirin") today announced the results of a Japanese late-phase 2 clinical trial of mogamulizumab (generic name/code name: KW-0761) for relapsed peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) have been presented at the 54th Annual Meeting of the American Society of Hematology (ASH), which was held in Atlanta, Georgia, between December 8-11, 2012.

Mogamulizumab is a humanized monoclonal antibody directed against CCR4 (CC chemokine receptor 4), which is expressed on malignant T cells, including PTCL cells and CTCL cells. Engineered by Kyowa Hakko Kirin's unique POTELLIGENT® Technology, this antibody is designed to kill its target cells through the potent antibody-dependent cellular cytotoxicity (ADCC).
The oral presentation (Abstract number: 795), pertained to a multicenter Phase 2 clinical trial in patients with CCR4-positive, relapsed PTCL and CTCL, was delivered by Dr. Takashi Ishida with the Medical Oncology and Immunology, Nagoya City University. This clinical trial was designed to evaluate the efficacy, safety, and pharmacokinetics of mogamulizumab at 1.0 mg/kg weekly for eight weeks in 37 patients. Common adverse events included hematotoxicities, such as lymphopenia, leukocytopenia, neutropenia, and thrombocytopenia, and non-hematological toxicities, such as fever, rush, and acute infusion reaction. However, the adverse events were considered tolerable as they could be managed with appropriate treatment. The study's primary endpoint for efficacy was overall response rate (ORR) and the results showed an ORR of 35% (95% CI; 20-53%), confirming that mogamulizumab is effective against CCR4-positive relapsed PTCL and CTCL.

Mogamulizumab was launched in Japan with the brand name "POTELIGEO® Injection 20 mg" on May 29, 2012 for the treatment of patients with relapsed or refractory CCR4-positive adult T-cell leukemia-lymphoma (ATL) and is being investigated world-wide in a number of clinical studies for other potential indications.

Kyowa Hakko Kirin is committed to developing innovative therapeutics for treatment of a wide range of diseases with unmet medical needs, including lymphomas such as PTCL and CTCL, and contributing to the improvement of patients' quality of life (QOL).


< Summary of the Japanese late-phase 2 clinical trial presented at ASH 54 >

1. Trial overview
Objectives: Evaluate the efficacy, safety and pharmacokinetics of mogamulizumab at 1.0 mg/kg weekly for eight weeks in patients with CCR4-positive relapsed PTCL and CTCL.
Primary endpoints: Efficacy (ORR), safety, pharmacokinetics

2. Key results presented
Efficacy: Efficacy was assessed in 37 patients
ORR:35% (95% CI; 20-53%)
PTCL:Remission in 10 of 29 patients
(complete response in 5 patients, partial response in 5 patients)
CTCL:Remission in 3 of 8 patients
(partial response in 3 patients)
Safety: Safety was assessed in 37 patients
Hematotoxicity:
Lymphopenia (30 patients), leukopenia (16 patients), thrombocytopenia (14 patients),
neutropenia (14 patients)
Non-hematotoxicity:
rash (19 patients), fever (11 patients), acute infusion reaction (9 patients), elevated ALT (8 patients), elevated ALP (8 patients)

About Peripheral T-Cell Lymphoma (PTCL)
Non-Hodgkin lymphomas account for the majority of malignant lymphoma cases and can be broadly divided into disease of B-cell origin and disease of T/natural killer (NK)-cell origin. Disease of T/NK-cell origin can be classified according to the main lesion site into nodal, extranodal, cutaneous, and leukemic disease. PTCL is a general term describing nodal and extranodal disease of T/NK-cell origin.

About Cutaneous T-Cell Lymphoma (CTCL)
CTCL is a rare, low grade type of non-Hodgkin's lymphoma. CTCL is one of the most common forms of T-cell lymphoma. The two most common types of CTCL are mycosis fungoides (MF) and Sezary syndrome (SS). MF does not look the same in all patients and may present as skin patches, plaques, and tumors. SS is an advanced form of MF and includes the presence of malignant lymphocytes in the blood.

About CCR4 (CC chemokine receptor 4)
CCR4 is one of the chemokine receptors involved in leukocyte migration, selectively expressed in type 2 helper T (Th2) cells and regulatory T (Treg) cells. CCR4 is also shown to be over-expressed in certain hematological malignancies.

About POTELLIGENT®
POTELLIGENT® is Kyowa Hakko Kirin's unique technology for the production of antibodies with enhanced ADCC activity. This technique enables production of antibodies with a reduced amount of fucose in their carbohydrate structure. Non-clinical studies have demonstrated that antibodies produced using this technology killed target cells more efficiently than conventional antibodies and exhibited stronger antitumor effects. For more information, please visit www.POTELLIGENT.com.

About antibody-dependent cellular cytotoxicity (ADCC)
ADCC is one of the body's immune responses, initiated by binding of an antibody to its antigen on target cells, followed by lysis of the antibody-bound target cells by effector cells such as natural killer cells. ADCC is known to be one of the modes of action of therapeutic antibodies.

About acute infusion reaction
When monoclonal antibodies are given as an intravenous infusion, acute side effects may sometimes occur. Acute infusion reaction is the general term describing side effects that occur rapidly during or after drug administration and subside within 24 hours. The reaction can involve mild to moderate symptoms such as rigors and fever, as well as severe symptoms such as dyspnea and bronchospasm. In some cases, preventive steps need to be taken and patients need to be managed appropriately and observed for symptoms.

About adult T-cell leukemia-lymphoma (ATL)
ATL is a peripheral T-cell malignancy and the retrovirus HTLV-1 is thought to be involved in its onset. Estimates show that around 1,150 new cases occur every year in Japan. ATL is generally treated with combination chemotherapy, such as mLSG15, but there are currently no therapeutic methods with the potential of providing a cure for ATL, although researchers are actively looking into other methods than transplantation. For relapsed/refractory cases, various chemotherapy regimens based on malignant lymphoma therapies are currently used, but an effective treatment method has yet to be established.



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