Pharmacyclics Reports IMRUVICA Data Shows Safety, Durability of Response at Two-Year Follow-Up in Mantle Cell Lymphoma

New, 27-month IMBRUVICA^® (ibrutinib) median follow-up data announced by Pharmacyclics, Inc.

today support the use of IMBRUVICA over longer periods of time in patients with relapsed/refractory mantle cell lymphoma (MCL), an aggressive type of lymphoma. More than 30% of IMBRUVICA patients remained progression-free after two years with no new or unexpected adverse events occurring during that time. Nearly half (47%) of the 111 patients treated were still living at the time of the data analysis. A second Phase II trial looked at IMBRUVICA's efficacy and safety as a single-agent treatment for MCL patients who previously had received rituximab combination therapy and at least two cycles of bortezomib. These data were presented here today at the 56th American Society of Hematology (ASH) Annual Meeting. IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. "These new data showing IMBRUVICA's ability to maintain a durable response with a favorable safety profile for over two years are very encouraging, particularly for those patients with relapsed disease in whom treatment options are limited," said Darrin Beaupre, M.D., Ph.D., Vice President, Clinical Medicine and Early Development, Pharmacyclics. Abstract 4453: Single-Agent Ibrutinib Demonstrates Safety and Durability of Response at 2 Years Follow-up in Patients with Relapsed or Refractory Mantle Cell Lymphoma: Updated Results of an International, Multi-center, Open-Label Phase 2 Study In the Phase II, multi-center, single-arm, open-label trial (PCYC-1104) in patients with relapsed/refractory mantle cell lymphoma, patients received IMBRUVICA once daily until disease progression or unacceptable toxicity (n=111). Patients were allowed to continue treatment through a long-term extension trial. While the median treatment duration in the trial was 8.3 months, 46% of patients received treatment for more than one year and 20% continued on treatment in the extension trial for more than two years. At 24 months, approximately one-third of patients (31%) remained progression-free and almost half (47%) remained alive. The median overall survival (OS) was 22.5 months and the median progression-free survival (PFS) was 13 months. Investigators observed a 67% overall response rate (ORR), which was the primary endpoint of the trial, and 23% of patients experienced a complete response. The median response time was less than two months (1.9 months) and the median duration of response was 17.5 months. "The positive results seen with IMBRUVICA treatment in MCL patients continue to support its use over longer periods of time and in patients with high-risk disease," said Michael Wang, M.D. from the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, Houston, TX, and lead investigator for the pivotal registration trial PCYC-1104^+ who presented the findings in an oral presentation today. Data from the follow-up analysis were consistent with earlier results from the trial, which served as the basis for the November 13, 2013 approval of IMBRUVICA for the treatment of patients with MCL who have received at least one prior therapy. Accelerated approval was granted for this indication based on ORR. Improvements in survival or disease-related symptoms have not been established. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials. With an estimated median follow up of 26.7 months, the most common Grade 3 or greater adverse events (AEs) in the trial were infection (28%), diarrhea (5%) and bleeding (6%). Serious adverse events (SAEs (>2), regardless of attribution, included: disease progression (10%); pneumonia (7%); atrial fibrillation (6%); and, urinary tract infection (4%). SAEs occurred in 21% of patients and generally both Grade >3 and SAE infections decreased over time. Abstract 4471: Efficacy and Safety of Single-Agent Ibrutinib in Patients with Mantle Cell Lymphoma Who Progressed after Bortezomib Therapy Dr. Wang also presented a second poster today highlighting the results from a Phase II, multi-center, single-arm trial (MCL2001), which investigated once-daily IMBRUVICA in patients with relapsed/refractory MCL who previously had received a rituximab-containing treatment regimen and had progressed after at least two cycles of bortezomib (n=120). An Independent Review Committee (IRC) found the ORR, which was the primary endpoint of the trial, was 63% after a median follow-up of 14.9 months and 21% of patients achieved a complete response. Secondary endpoints included duration of response (DOR) PFS, OS and safety. The median DOR based on IRC assessment was 14.9 months and the median time to first response was 2.1 months. The median PFS was 10.5 months, with 47% of patients remaining progression-free at one year. The median PFS has not yet been reached. The OS rate at 18 months was 61%. The most frequently reported AEs of any grade were fatigue (43%) and diarrhea (43%). Diarrhea, when observed generally occurred early after initial treatment, but resolved quickly and was not treatment limiting. The majority of AEs were grade 1 and 2. The most common AEs > grade 3 were neutropenia (21%), thrombocytopenia (13%) and pneumonia (13%). Atrial fibrillation was reported in 13 patients (11%); six patients (5%) experienced Grade 3 or 4 atrial fibrillation which resolved in 1 to 4 days. Five of these six patients had a history of atrial fibrillation.