Kyowa Hakko Kirin Announces Results of Phase 3 Clinical Study of Mogamulizumab Published in Lancet Oncology

Kyowa Hakko Kirin Co., Ltd., (Kyowa Kirin) announced today that results of the global Phase 3 MAVORIC study (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) investigating the use of mogamulizumab in patients with cutaneous T-cell lymphoma (CTCL) have been published in Lancet Oncology (DOI: https://doi.org/10.1016/S1470-2045(18)30379-6). MAVORIC was the open-label randomized multi-center phase 3 trial that evaluated mogamulizumab versus vorinostat for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. MF and SS are the most common subtypes of CTCL.

MAVORIC is the first pivotal trial to use progression free survival (PFS) as a primary endpoint and the largest randomized study to compare systemic therapies in CTCL. Secondary endpoints included proportion of patients achieving an overall response (ORR), duration of response (DOR) and safety. It was the pivotal study included in the Biologics License Application (BLA) that was recently approved by the U.S. Food and Drug Administration (FDA).

"Progression-free survival captures the duration of disease control with treatment based on the composite response assessment of each disease compartment, skin, blood, lymph nodes, and viscera, and may more broadly reflect the overall impact of new therapies," said Youn Kim, lead investigator and Professor of Dermatology/Medicine and Director of the Multidisciplinary Cutaneous Lymphoma Program at Stanford University School of Medicine and Stanford Cancer Institute. "Progression-free survival is more informative about the duration of overall clinical benefit for patients with a chronic course as in CTCL compared to using the overall response rate as a primary endpoint."

In MAVORIC, 372 patients across 61 centers in 11 countries were randomized 1:1 to mogamulizumab or vorinostat and stratified by CTCL subtype (MF or SS) and disease stage (IB/II or III/IV). Once enrolled, patients received either mogamulizumab 1.0 mg/kg or vorinostat 400 mg and each treatment cycle was 28 days. Patients on vorinostat who demonstrated confirmed disease progression or experienced intolerable toxicity after two cycles, despite dose reduction and appropriate management of side effects, could cross over to treatment with mogamulizumab.

The results showed that mogamulizumab demonstrated significantly superior PFS at a median of 7.7 months [95% CI, 5.7, 10.3] compared to 3.1 months with vorinostat [95% CI, 2.9, 4.1; hazard ratio 0.53, 95% CI 0.41- 0.6969; p<0.0001]. In addition to meeting the primary endpoint, ORR [28%; 95% CI, 21.6, 35.0 vs. 4.8%; 95% CI, 2.2, 9.0], median DOR [14.1 months, IQR 8.4-19.2 vs. 9.1 months (IQR 5.6 - not estimable)] and response by disease compartment were higher for patients assigned to mogamulizumab than for patients assigned to vorinostat. The safety profile of mogamulizumab was consistent with previous studies and the most common adverse events of any grade included infusion-related reactions (33%) and drug rash (24%). Infusion-related reactions were manageable and mostly limited to early infusions. Grade 3-4 adverse events were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group.

"Mycosis fungoides and Sézary syndrome can be debilitating for patients and complex to treat and manage for healthcare professionals," said Jeffrey S. Humphrey, MD, Chief Medical Officer and President of Kyowa Kirin Pharmaceutical Development, Inc. "We are encouraged that these findings underscore the viability of mogamulizumab as a new treatment option for patients living with MF or SS."

The Kyowa Hakko Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

Please see Poteligeo indication and Important Safety Information below.

INDICATION
POTELIGEO^® (mogamulizumab-kpkc) injection, for intravenous infusion is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.

Important Safety Information

Warnings and Precautions:

• Dermatologic toxicity: Monitor patients for rash throughout the course of treatment. For patients who experienced dermatologic toxicity in Trial 1, the median time to onset was 15 weeks, with 25% of cases occurring after 31 weeks. Interrupt POTELIGEO for moderate or severe rash (Grades 2 or 3). Permanently discontinue POTELIGEO for life-threatening (Grade 4) rash or for any Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).
• Infusion reactions: Most infusion reactions occur during or shortly after the first infusion. Infusion reactions can also occur with subsequent infusions. Monitor patients closely for signs and symptoms of infusion reactions and interrupt the infusion for any grade reaction and treat promptly. Permanently discontinue POTELIGEO for any life-threatening (Grade 4) infusion reaction.
• Infections: Monitor patients for signs and symptoms of infection and treat promptly.
• Autoimmune complications: Interrupt or permanently discontinue POTELIGEO as appropriate for suspected immune-mediated adverse reactions. Consider the benefit/risk of POTELIGEO in patients with a history of autoimmune disease.
• Complications of allogeneic HSCT after POTELIGEO: Increased risks of transplant complications have been reported in patients who received allogeneic HSCT after POTELIGEO. Follow patients closely for early evidence of transplant-related complications.

Adverse Reactions:

• The most common adverse reactions (reported in ≥ 10% of patients) with POTELIGEO in the clinical trial were rash, including drug eruption (35%), infusion reaction (33%), fatigue (31%), diarrhea (28%), drug eruption (24%), upper respiratory tract infection (22%), musculoskeletal pain (22%), skin infection (19%), pyrexia (17%), edema (16%), nausea (16%), headache (14%), thrombocytopenia (14%), constipation (13%), anemia (12%), mucositis (12%), cough (11%), and hypertension (10%).

You are encouraged to report suspected adverse reactions to Kyowa Kirin, Inc. at 1-844-768-3544 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

About Kyowa Kirin
Kyowa Hakko Kirin Co., Ltd. is a research-based life sciences company, with special strengths in biotechnologies. In the core therapeutic areas of oncology, nephrology and immunology/allergy, Kyowa Hakko Kirin leverages leading-edge biotechnologies centered on antibody technologies, to continually discover innovative new drugs and to develop and market those drugs world-wide. In this way, the company is working to realize its vision of becoming a Japan-based global specialty pharmaceutical company that contributes to the health and wellbeing of people around the world. Kyowa Kirin International PLC is a wholly owned subsidiary of Kyowa Hakko Kirin and is a rapidly growing specialty pharmaceutical company engaged in the development and commercialization of prescription medicines for the treatment of unmet therapeutic needs in Europe and the United States. Kyowa Kirin International is headquartered in Scotland. You can learn more about the business at: www.kyowa-kirin.com.

About Poteligeo
Poteligeo is a humanized monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4), which is frequently expressed on leukemic cells of certain hematologic malignancies including CTCL (cutaneous T-cell lymphoma).

About mycosis fungoides (MF) and Sézary Syndrome (SS)
MF and SS are the two most common subtypes of CTCL, a rare type of non-Hodgkin's lymphoma, which is characterized by localization of malignant T lymphocytes to the skin, and depending on the stage, the disease may involve skin, blood, lymph nodes, and viscera.

About MAVORIC
MAVORIC is a Phase 3 open-label, multi-center, randomized study of mogamulizumab versus vorinostat in patients with MF and SS who have failed at least one prior systemic treatment. The study was conducted in the U.S., Europe, Japan and Australia, and randomized 372 patients to receive either mogamulizumab or vorinostat.

Potelligent® is a registered trademark of Kyowa Hakko Kirin, Co., Ltd.

©2018 Kyowa Hakko Kirin, Co., Ltd. All Rights Reserved.

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