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. (NASDAQ: PCYC) today support the use of IMBRUVICA over longer periods of time inpatients with relapsed/refractory mantle cell lymphoma (MCL), an aggressivetype of lymphoma. More than 30% of IMBRUVICA patients remainedprogression-free after two years with no new or unexpected adverse eventsoccurring during that time. Nearly half (47%) of the 111 patients treated werestill living at the time of the data analysis. A second Phase II trial lookedat IMBRUVICA's efficacy and safety as a single-agent treatment for MCLpatients who previously had received rituximab combination therapy and atleast two cycles of bortezomib. These data were presented here today at the56th American Society of Hematology (ASH) Annual Meeting. IMBRUVICA is jointlydeveloped and commercialized by Pharmacyclics and Janssen Biotech, Inc."These new data showing IMBRUVICA's ability to maintain a durable responsewith a favorable safety profile for over two years are very encouraging,particularly for those patients with relapsed disease in whom treatmentoptions 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 ofResponse at 2 Years Follow-up in Patients with Relapsed or Refractory MantleCell Lymphoma: Updated Results of an International, Multi-center, Open-LabelPhase 2 StudyIn the Phase II, multi-center, single-arm, open-label trial (PCYC-1104) inpatients with relapsed/refractory mantle cell lymphoma, patients receivedIMBRUVICA once daily until disease progression or unacceptable toxicity(n=111). Patients were allowed to continue treatment through a long-termextension trial. While the median treatment duration in the trial was 8.3months, 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 24months, approximately one-third of patients (31%) remained progression-freeand almost half (47%) remained alive. The median overall survival (OS) was22.5 months and the median progression-free survival (PFS) was 13 months.Investigators observed a 67% overall response rate (ORR), which was theprimary endpoint of the trial, and 23% of patients experienced a completeresponse. The median response time was less than two months (1.9 months) andthe median duration of response was 17.5 months."The positive results seen with IMBRUVICA treatment in MCL patients continueto support its use over longer periods of time and in patients with high-riskdisease," said Michael Wang, M.D. from the Department of Lymphoma/Myeloma atThe University of Texas MD Anderson Cancer Center, Houston, TX, and leadinvestigator for the pivotal registration trial PCYC-1104^+ who presented thefindings in an oral presentation today.Data from the follow-up analysis were consistent with earlier results from thetrial, which served as the basis for the November 13, 2013 approval ofIMBRUVICA for the treatment of patients with MCL who have received at leastone prior therapy. Accelerated approval was granted for this indication basedon ORR. Improvements in survival or disease-related symptoms have not beenestablished. Continued approval for this indication may be contingent uponverification of clinical benefit in confirmatory trials.With an estimated median follow up of 26.7 months, the most common Grade 3 orgreater adverse events (AEs) in the trial were infection (28%), diarrhea (5%)and bleeding (6%). Serious adverse events (SAEs (>2), regardless ofattribution, included: disease progression (10%); pneumonia (7%); atrialfibrillation (6%); and, urinary tract infection (4%). SAEs occurred in 21% ofpatients and generally both Grade >3 and SAE infections decreased over time.Abstract 4471: Efficacy and Safety of Single-Agent Ibrutinib in Patients withMantle Cell Lymphoma Who Progressed after Bortezomib TherapyDr. Wang also presented a second poster today highlighting the results from aPhase II, multi-center, single-arm trial (MCL2001), which investigatedonce-daily IMBRUVICA in patients with relapsed/refractory MCL who previouslyhad received a rituximab-containing treatment regimen and had progressed afterat 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 acomplete response. Secondary endpoints included duration of response (DOR)PFS, OS and safety. The median DOR based on IRC assessment was 14.9 months andthe median time to first response was 2.1 months. The median PFS was 10.5months, with 47% of patients remaining progression-free at one year. Themedian 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 initialtreatment, but resolved quickly and was not treatment limiting. The majorityof AEs were grade 1 and 2. The most common AEs > grade 3 were neutropenia(21%), thrombocytopenia (13%) and pneumonia (13%). Atrial fibrillation wasreported in 13 patients (11%); six patients (5%) experienced Grade 3 or 4atrial fibrillation which resolved in 1 to 4 days. Five of these six patientshad a history of atrial fibrillation.