Pharmacyclics has submitted a supplemental New Drug Application (sNDA) to the FDA, based on data from the randomized, multi-center, open-label phase III RESONATE study, PCYC-1112, a head-to-head comparison of single agent IMBRUVICA (ibrutinib) versus ofatumumab in 391 patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who had received at least one prior therapy. IMBRUVICA is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech.
At a planned interim analysis in January, the results of the RESONATE study demonstrated a statistically significant improvement in progression-free survival, the primary endpoint of the study, in patients treated with IMBRUVICA. Further, patients in the IMBRUVICA arm also showed a statistically significant improvement in overall survival, a key secondary endpoint of the trial. The safety profile of IMBRUVICA was acceptable and showed a favorable risk benefit profile.
"This sNDA in previously treated CLL patients is our first phase III submission to the FDA seeking full approval for the use of IMBRUVICA. It is another major milestone in our clinical development plan, which currently includes 10 phase III studies," said Bob Duggan, CEO and chairman of the board of Pharmacyclics. "Our company's mission is to serve as an ally to patients. In the RESONATE study, single agent IMBRUVICA provided a significant benefit for patients with CLL. We look forward to working with the FDA as they review the data from this phase III study."
The FDA granted an accelerated approval for IMBRUVICA as a single agent for the treatment of patients with MCL or CLL, who have received at least one prior therapy. The accelerated approval for these indications was based on the overall response rate (ORR) of patients in the phase II clinical studies of PCYC-1102 and PCYC-1104. An improvement in survival or disease-related symptoms was not established in these studies. IMBRUVICA is the first once-daily, single-agent, oral kinase inhibitor for patients with MCL or CLL who have received one prior therapy.
CLL is a slow-growing blood cancer of the white blood cells (lymphocytes), most commonly B-cells. CLL is the most common adult leukemia. Approximately 16,000 patients in the U.S. are diagnosed each year with CLL. The prevalence of CLL is approximately 114,500 in the U.S. CLL is a chronic disease that predominantly occurs in the elderly and the average age of diagnosis is 72.The five-year survival is approximately 82%.
MCL also is a blood cancer; it is an aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in older adults. The disease typically involves the lymph nodes, but can spread to other tissues, such as bone marrow, liver, spleen and gastrointestinal tract. The prevalence of MCL is approximately 11,300 in the U.S. and patients survive an average of five years.
CLL and MCL are both classified as orphan or rare diseases, defined as agents, which affect fewer than 200,000 Americans. Patients commonly receive multiple lines of treatment over the course of their disease.