The US Food and Drug Administration (FDA) has accepted Pharmacyclics' filing of New Drug Application (NDA) for the investigational oral Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, for two B-cell malignancy indications: previously treated mantle cell lymphoma (MCL) and previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

On June 28, 2013 Pharmacyclics submitted a New Drug Application (NDA) under section 505(b) of the Food, Drug & Cosmetic Act for ibrutinib. On August 27, 2013 the FDA notified Pharmacyclics that they have completed their filing review and determined that the application is sufficiently complete to permit a substantive review. The FDA's acceptance of the NDA triggers a $75 million milestone payment to Pharmacyclics under its collaboration agreement with Janssen Biotech Inc.

"We are very excited to have received the official FDA acceptance of our first NDA filing for ibrutinib," said Dr. Urte Gayko, senior vice president of global regulatory affairs, Pharmacyclics. "We look forward to continuing to work with the FDA as they complete their review of the ibrutinib application which includes the new breakthrough therapy designation process."

CLL, a B-cell malignancy, is a slow-growing blood cancer of the white blood cells (lymphocytes), most commonly from B-cells. CLL is the second most common adult leukemia. Approximately 16,000 patients in the US are diagnosed each year with CLL. The prevalence of CLL is approximately 113,000 in the US.  CLL is a chronic disease that predominantly occurs in the elderly with a five-year survival of approximately 82 per cent. Patients commonly receive multiple lines of treatment over the course of their disease. When cancer cells are located mostly in the lymph nodes, the disease is called SLL. CLL and SLL are considered to be different manifestations of the same underlying disease; they share similarities in signs and symptoms, genetic features, disease progression and treatment.

MCL is a B-cell malignancy, an aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in older adults. The disease typically begins in the lymph nodes, but can spread to other tissues, such as bone marrow, liver, and spleen. Patients typically survive an average of five years.4 In the US, there are approximately 2,500 new cases of MCL each year and a prevalence of approximately 10,000 (Decision Resources 2012).

Ibrutinib is an investigational agent designed to provide potent and sustained inhibition of an enzyme called Bruton's tyrosine kinase (BTK). BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel — regulation of apoptosis, adhesion, and cell migration and homing. Through these multiple signals, BTK regulation helps to direct malignant B-cells to lymphoid tissues, thus allowing access to a micro-environment necessary for survival.

The effectiveness of ibrutinib alone or in combination with other treatments is being studied in several B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Waldenstrom's macroglobulinemia and multiple myeloma. To date, 7 Phase III trials have been initiated with ibrutinib and a total of 31 trials are currently registered on www.clinicaltrials.gov. Janssen and Pharmacyclics entered a collaboration and license agreement in December 2011 to co-develop and co-commercialize ibrutinib.

Pharmacyclics is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative small-molecule drugs for the treatment of cancer and immune mediated diseases.