Pharmacyclics Release: IMBRUVICA (ibrutinib) Longer-Term Follow-Up Data Demonstrate Durable Responses, Including Complete Responses, In Patients With Chronic Lymphocytic Leukemia (CLL)

PHILADELPHIA, April 20, 2015 /PRNewswire/ -- Pharmacyclics, Inc. (NASDAQ: PCYC) today announced that IMBRUVICA^® (ibrutinib) follow-up data in treatment-naive (TN) and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL or SLL, respectively) demonstrated that, with up to 45 months of follow-up, the 94 patients (27 TN and 67 R/R) who received IMBRUVICA 420 mg experienced a 91% overall response rate (ORR) and 14% of all patients achieved a complete response (CR) (26% TN, 9% R/R). These data are an analysis of outcomes from the Phase I/IIb study (PCYC-1102) and the ongoing extension study (PCYC-1103) and were presented in an oral presentation yesterday at the American Association of Cancer Research (AACR) Annual Meeting in Philadelphia, PA by Steven Coutre, M.D., Professor of Medicine, Stanford University School of Medicine, Stanford, CA. IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.

The median treatment duration was 25 months (range, 0-45 months) for all patients (30 months TN; 22 months R/R). The median duration of response (DOR) and progression-free survival (PFS) have not yet been reached. The 30-month PFS rate was 96% in TN and 76% in R/R CLL patients. The median number of prior therapies for R/R patients was four (range, 1-12 therapies). One patient with previously untreated CLL experienced disease progression during the follow-up.

"These data focused on the recommended 420 mg dose for CLL patients and demonstrate the continued efficacy and tolerability of IMBRUVICA, supporting its use as a longer-term, single-agent, oral treatment option for patients with CLL," said Danelle James, M.D., M.S., Head of Oncology at Pharmacyclics.

The majority of patients entered the study with baseline cytopenias. Early and sustained improvement in hemoglobin and platelet counts were observed. The most frequently reported Grade 3 or greater adverse events (AEs) in the trial were hypertension (23%), pneumonia (15%), neutropenia (13%), atrial fibrillation (7%) and diarrhea (7%). During follow-up, 12 patients discontinued treatment due to disease progression. Discontinuation due to AEs declined over time; in total, 12 patients discontinued due to an AE (seven patients in year 1, three patients in year 2, and two patients beyond year 3).

About Chronic Lymphocytic Leukemia (CLL)

The prevalence of CLL/SLL is approximately 115,000 patients in the United States,¹ with approximately 16,000 newly diagnosed patients every year.² As this orphan disease frequently progresses following first-line therapy, patients are faced with fewer treatment options and often are prescribed multiple lines of therapy as they relapse or become resistant to treatments.³

In CLL/SLL, the genetic mutation del 17p occurs when part of chromosome 17 has been lost or deleted. CLL/SLL patients with del 17p have poor treatment outcomes.⁴ Del 17p is reported in approximately 7% of treatment-naive CLL/SLL cases,⁵ and approximately 20% to 40% of relapsed/refractory patients harbor the mutation.⁶

About IMBRUVICA
IMBRUVICA is currently approved for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, all CLL patients (including treatment-naive) who have del 17p, a genetic mutation that occurs when part of chromosome 17 has been lost, and all patients (including treatment-naive) with Waldenstrom's macroglobulinemia.⁷ IMBRUVICA is also approved under accelerated approval for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.⁷

IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton's tyrosine kinase (BTK).⁷ IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway, and is the only product to have received three Breakthrough Therapy Designations.

BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.^7,8 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.⁷

IMBRUVICA is being studied alone and in combination with other treatments in several blood cancers. Over 5,100 patients have been treated in clinical trials of IMBRUVICA conducted in 35 countries by more than 800 investigators. Currently, 13 Phase III trials have been initiated with IMBRUVICA and 60 trials are registered on www.clinicaltrials.gov.

To learn more about the medical terminology used in this news release, please visit http://stedmansonline.com/.

INDICATIONS

IMBRUVICA is indicated to treat people with:

• Chronic lymphocytic leukemia (CLL) who have received at least one prior therapy
• Chronic lymphocytic leukemia (CLL) with 17p deletion
• Waldenstrom's macroglobulinemia
• Mantle cell lymphoma (MCL) who have received at least one prior therapy accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

Patients taking IMBRUVICA for CLL or WM should take 420 mg taken orally once daily (or three 140 mg capsules once daily).

Patients taking IMBRUVICA for MCL should take 560 mg taken orally once daily (or four 140 mg capsules once daily).

Capsules should be taken orally with a glass of water. Capsules should be taken whole. Do not open, break, split or chew the capsules.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage - Fatal bleeding events have occurred in patients treated with IMBRUVICA^®. Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA^®.

The mechanism for the bleeding events is not well understood. IMBRUVICA^® may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies. Consider the benefit-risk of withholding IMBRUVICA^® for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections - Fatal and non-fatal infections have occurred with IMBRUVICA^® therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA^®. Monitor patients for fever and infections and evaluate promptly.

Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 9%) occurred in patients treated with IMBRUVICA^®. Monitor complete blood counts monthly.

Atrial Fibrillation - Atrial fibrillation and atrial flutter (range, 6 to 9%) have occurred in patients treated with IMBRUVICA^®, particularly in patients with cardiac risk factors, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. If atrial fibrillation persists, consider the risks and benefits of IMBRUVICA^® treatment and dose modification.

Second Primary Malignancies - Other malignancies (range, 5 to 14%) including non-skin carcinomas (range, 1 to 3%) have occurred in patients treated with IMBRUVICA^®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4 to 11%).

Tumor Lysis Syndrome - Tumor lysis syndrome has been reported with IMBRUVICA^® therapy. Monitor patients closely and take appropriate precautions in patients at risk for tumor lysis syndrome (e.g. high tumor burden).

Embryo-Fetal Toxicity - Based on findings in animals, IMBRUVICA^® can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA^®. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS

The most common adverse reactions (>25%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, bruising, nausea, upper respiratory tract infection, and rash. Seven percent of patients receiving IMBRUVICA^® discontinued treatment due to adverse events.

DRUG INTERACTIONS

CYP3A Inhibitors - Avoid co-administration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA^® dose.

CYP3A Inducers - Avoid co-administration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment - Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA^® dose.

For additional important safety information, please see Full Prescribing Information at http://www.imbruvica.com/downloads/Prescribing_Information.pdf.

About Pharmacyclics

Pharmacyclics, Inc. (NASDAQ: PCYC) is a biopharmaceutical company focused on developing and commercializing innovative small-molecule drugs for the treatment of cancer and immune mediated diseases. The company's mission 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 needs. It will do so by identifying and controlling promising product candidates based on scientific development and administrative expertise, developing its products in a rapid, cost-efficient manner and, pursuing commercialization and/or development partners when and where appropriate.

Pharmacyclics markets IMBRUVICA and has three 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 commercialization. Pharmacyclics is headquartered in Sunnyvale, CA. To learn more, please visit 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, including our expected liquidity position and timing of the receipt of certain milestone payments, 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", "goal", "should", "would", "project", "plan", "predict", "intend", "target" 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, expected liquidity 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 Form 10-K for the year ended December 31, 2013 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.

IMBRUVICA is a registered trademark of Pharmacyclics, Inc.

[1] IMS Database [Data on File]

[2] American Cancer Society. What are the key statistics for chronic lymphocytic leukemia? Available from: http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-key-statistics. Accessed April 2015.

[3] Veliz M, Pinilla-Ibarz J. Cancer Control. Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia. January 2012, Vol. 19, No. 1.

[4] NCCN Clinical Practice Guidelines in Oncology. Non-Hodgkins Lymphomas. Version 1.2014. http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf. Accessed April 2015.

[5] Schnaiter A, Stilgenbauer S. 17p deletion in chronic lymphocytic leukemia: risk stratification and therapeutic approach. Hematol Oncol Clin North Am. 2013;27:289-301.

[6] Stilgenbauer S, Zenz T. Understanding and managing ultra high-risk chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2010;2010: 481-8.

[7] IMBRUVICA Prescribing Information, January 2015  

[8] Genetics Home Reference. Isolated growth hormone deficiency. Available at: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed April 2015.

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