Ibrutinib Study Results in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Published in The New England Journal of Medicine

SUNNYVALE, Calif., June 19, 2013 /PRNewswire/ -- Pharmacyclics, Inc. (the "Company") (Nasdaq: PCYC) today announced that The New England Journal of Medicine (NEJM) published results online of a Phase 1b/2 study evaluating the investigational oral Bruton's tyrosine kinase (BTK) inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Ibrutinib was shown to be safe and effective in patients with relapsed/refractory CLL or SLL, even in patients who were at high-risk due to factors such as deletion of part of chromosome 17 (del 17p).

Results of a separate study examining the safety and efficacy of ibrutinib monotherapy for the treatment of relapsed/refractory mantle cell lymphoma (MCL) has also been published online in NEJM today. Pharmacyclics sponsored both studies and is jointly developing ibrutinib with Janssen Research & Development, LLC.

The open-label study reported on 85 patients with relapsed/refractory CLL or SLL. The majority of patients had advanced disease and had previously undergone treatment with several rounds of therapies before enrollment in the study. Approximately one-third of patients enrolled in the study presented with a malignancy carrying del 17p. Patients with del17p typically respond poorly to chemoimmunotherapy, which is the current standard treatment for CLL.

"Patients with CLL and SLL have a great need for new, well tolerated and effective therapies," said lead author John C. Byrd, M.D., Director, Division of Hematology, D Warren Brown Professor of Leukemia Research, The Ohio State University Comprehensive Cancer Center. "These data are particularly exciting, as they demonstrate benefit for high risk CLL and SLL patients, with efficacy consistent across doses and continuing durable remissions lasting in excess of two years in the great majority of patients treated."  

Study participants were enrolled selected to receive either ibrutinib 420 mg (n=51) or 840 mg (n=34) as a once-daily, oral monotherapy. Both doses were associated with overall response rates of 71 percent. Del17p patients had an overall response rate of 68 percent. Two patients in the 420 mg dose arm had complete responses and 34 patients had partial responses. Across all relapsed or refractory patients, including the high risk patients, the estimated progression-free survival at 26 months was 75 percent. An additional 20 percent of patients treated with the 420 mg dose and 15 percent of patients taking the 840 mg dose achieved a partial response accompanied by lymphocytosis, an elevated blood lymphocyte count.

The majority of adverse events (AEs) observed in the study were considered to be Grade 1 or 2 in severity, including diarrhea, infections and fatigue. A total of six patients taking ibrutinib experienced an AE leading them to discontinue treatment with the drug. Severe AEs observed during the treatment period include pneumonia and dehydration (12 percent and six percent, respectively), as well anemia, neutropenia and thrombocytopenia (six percent, 15 percent and six percent, respectively). Grade 3-4 hematological toxicities were not common.

Data from this study were presented at the annual meeting of the American Society of Hematology in December 2012.

Study Design
The Phase 1b/2, open-label, multicenter study was designed to determine the safety, efficacy, pharmacokinetics and pharmacodynamics of ibrutinib in patients with relapsed or refractory CLL. The primary objective of the study was to determine the safety of the two fixed-dose regimens of ibrutinib, assessed by evaluating the frequency and severity of AEs. Secondary efficacy endpoints included: overall response rate, progression-free survival and an exploratory endpoint of overall survival.

The study enrolled patients with a confirmed diagnosis of relapsed or refractory CLL or small lymphocytic lymphoma (a disease that mirrors the symptoms and progression of CLL) at eight sites in the U.S. Patients who participated in the study had a median of four prior therapies and 65 percent of the patients had advanced disease. Twenty-eight CLL patients had del17p, a genetic mutation associated with a poor prognosis.

About CLL
CLL is a slow-growing blood cancer that starts in the white blood cells (lymphocytes), specifically the B-cells. CLL is the 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. It is a chronic disease of the elderly with an average survival of about five years after diagnosis. Patients commonly receive multiple lines of treatment over the course of their disease.

In CLL the genetic mutation del17p occurs when the short arm of chromosome 17 is missing. Del17p is associated with abnormalities of a key tumor suppressor gene, TP53, which results in poor response to chemoimmunotherapy and worse treatment outcomes. It occurs in about seven percent of treatment naïve CLL patients, with approximately 20-40 percent of relapsed/refractory patients harboring the mutation.  

About ibrutinib
Ibrutinib was designed to specifically target and selectively inhibit an enzyme called BTK. BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel – regulating B-cell apoptosis, cell adhesion, and lymphocyte migration and homing. Through these multiple actions, BTK helps to direct malignant B-cells to lymphoid tissues, thus allowing access to a microenvironment 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, relapsed/refractory mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma and multiple myeloma. The clinical development program currently includes 30 clinical trials, including six Phase 3 trials. Details about the complete ibrutinib clinical program is posted on clinicaltrials.gov. Janssen Biotech, Inc. and Pharmacyclics entered a collaboration and license agreement in December 2011 to co-develop and co-commercialize ibrutinib.

About Pharmacyclics
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. Our mission and goal is to build a viable biopharmaceutical company that designs, develops and commercializes novel therapies intended to improve quality of life, increase duration of life and resolve serious unmet medical healthcare needs; and to identify promising product candidates based on scientific development expertise, develop our products in a rapid, cost-efficient manner and pursue commercialization and/or development partners when and where appropriate.

Presently, Pharmacyclics has two product candidates in clinical development and several preclinical molecules in lead optimization. The Company is committed to high standards of ethics, scientific rigor, and operational efficiency as it moves each of these programs to viable commercialization.

The Company is headquartered in Sunnyvale, California and is listed on NASDAQ under the symbol PCYC. To learn more about how Pharmacyclics advances science to improve human healthcare visit us at http://www.pharmacyclics.com.  

NOTE: This announcement may contain forward-looking statements made in reliance upon the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements, among others, relating to our future capital requirements and the sufficiency of our current assets to meet these requirements, our future results of operations, our expectations for and timing of ongoing or future clinical trials and regulatory approvals for any of our product candidates, and our plans, objectives, expectations and intentions. Because these statements apply to future events, they are subject to risks and uncertainties. When used in this announcement, the words "anticipate", "believe", "estimate", "expect", "expectation", "should", "would", "project", "plan", "predict", "intend" and similar expressions are intended to identify such forward-looking statements. These forward-looking statements are based on information currently available to us and are subject to a number of risks, uncertainties and other factors that could cause our actual results, performance or achievements to differ materially from those projected in, or implied by, these forward-looking statements. Factors that may cause such a difference include, without limitation, our need for substantial additional financing and the availability and terms of any such financing, the safety and/or efficacy results of clinical trials of our product candidates, our failure to obtain regulatory approvals or comply with ongoing governmental regulation, our ability to commercialize, manufacture and achieve market acceptance of any of our product candidates, for which we rely heavily on collaboration with third parties, and our ability to protect and enforce our intellectual property rights and to operate without infringing upon the proprietary rights of third parties. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, performance or achievements and no assurance can be given that the actual results will be consistent with these forward-looking statements. For more information about the risks and uncertainties that may affect our results, please see the Risk Factors section of our filings with the Securities and Exchange Commission, including our annual report on Form 10-K and quarterly reports on Form 10-Q. We do not intend to update any of the forward-looking statements after the date of this announcement to conform these statements to actual results, to changes in management's expectations or otherwise, except as may be required by law.

Contact:
Ramses Erdtmann
Vice President of Investor Relations and Corporate Communications
Phone: 408-215-3325

U.S. Medical Information, Pharmacyclics:
855-Ibrutinib [(855) 427-8846]

SOURCE Pharmacyclics, Inc.



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