New Marketing Authorisation Application submitted to EMA for Ibrutinib for the treatment of two forms of blood cancer

Janssen-Cilag International NV (Janssen) announced today it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for ibrutinib for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) or relapsed or refractory mantle cell lymphoma (MCL), two forms of blood cancer.

Ibrutinib is administered orally, once-daily and is the first in a class of medicines called Bruton’s tyrosine kinase (BTK) inhibitors. Data suggest ibrutinib covalently bonds to BTK in malignant B cells, shutting down major proliferation and survival pathways. Ibrutinib is being developed by Janssen with Pharmacyclics, Inc. for the treatment of several forms of blood cancer. If approved, ibrutinib will be the first commercially available therapy targeting BTK.

“The EMA Marketing Authorisation Application is an important milestone in the development of ibrutinib,” said Jane Griffiths, Group Company Chairman of Janssen Europe, the Middle East and Africa (EMEA). ”At Janssen, we are dedicated to developing solutions that prolong and improve the lives of patients. If approved, ibrutinib will address a great unmet need for patients with CLL/SLL and MCL who have previously failed or become resistant to previous treatment.”

The EMA filings follow the New Drug Application submission of ibrutinib to the U.S. Food and Drug Administration which was announced on 10 July 2013, for its use in the treatment of previously treated patients with CLL/SLL or MCL.

CLL/SLL and MCL belong to a group of blood cancers, known as B-cell malignancies, originating from B cells, a type of white blood cell (lymphocyte).¹ CLL/SLL and MCL, are complex diseases that can be challenging to treat. As a result, many patients will relapse after a specific treatment and may require multiple treatments over the course of their disease.

About Ibrutinib

Ibrutinib is the first in a class of medicines called Bruton’s tyrosine kinase (BTK) inhibitors. BTK is an important protein involved in mediating the cellular signaling pathways which control B cell maturation and survival. In malignant B cells, there is excessive signaling through the B cell receptor signaling (BCR) pathway, which includes BTK. The malignant cell ignores the natural signal to die and continues to develop and proliferate. Malignant cells migrate and adhere to protective environmental areas such as the lymph nodes where they proliferate and survive. Ibrutinib is the first in a new class of drugs specifically designed to target and inhibit BTK. Ibrutinib forms a strong covalent bond with BTK, which inhibits the excessive transmission of cell survival signals within the malignant B cells and stops their excessive build up in these protected environmental areas. The efficacy and safety of ibrutinib alone and in combination with other treatments is being studied in several blood cancers.^2,3,4,5,6

About Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL)

CLL is a usually slow growing blood cancer that most commonly originates from B cells, a type of white blood cell (lymphocyte) that develops in the bone marrow. B cells are part of the immune system and play an important role in fighting infection in the body. CLL is the most common adult leukemia in the Western world, with the median age at diagnosis being primarily those over 70 years old. The incidence rates among men and women in Europe are approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively. CLL is a chronic disease; median overall survival ranges between 18 months and more than 10 years according to the stage of disease. When cancer cells are located mostly in the lymph nodes, the disease is called small lymphocytic lymphoma (SLL).^{7,8,9,10,11,12}

About Mantle Cell Lymphoma (MCL)

MCL is a rare and aggressive blood cancer that usually occurs in older adults, with the median age at diagnosis being 65 years. The disease typically begins in the bone marrow, but can spread to other tissues such as bone marrow, liver and spleen. The incidence rates among men and women in Europe are approximately 0.64 and 0.27 cases per 100,000 persons per year, respectively. MCL patients generally have a poor prognosis. Median overall survival is typically three to four years, and only one to two years in patients following the first relapse. ^13,14,15

References

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8. SEER Statistics. Fact Sheets: Chronic lymphocytic leukemia. Available from: http://seer.cancer.gov/statfacts/html/clyl.html. Accessed March 6, 2013.
9. American Cancer Society. Detailed guide: what is chronic lymphocytic leukemia. Available from: http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-what-is-cll. Accessed March 6, 2013.
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11. Cancer Research UK. The most common types of non-Hodgkins lymphoma. Available from: http://www.cancerresearchuk.org/cancerhelp/type/non-hodgkins-lymphoma/about/types/the-most-common-types-of-non-hodgkins-lymphoma#sll. Accessed March 14, 2013.
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13. McKay P, Leach M, Jackson R, et al. Guidelines for the investigation and management of mantle cell lymphoma. Br J Haematol 2012;159:405-26.
14. Leukemia and Lymphoma Society. Mantle Cell Lymphoma Facts. Available from: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/lymphoma/pdf/mantlecelllymphoma.pdf. Accessed May 14, 2013.
15. Smedby KE, Hjalgrim H. Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes. Semin Cancer Biol 2011;21:293-8.