Ibrutinib Phase 2 Study Results in Patients with Mantle Cell Lymphoma Published

Update: Imbruvica (ibrutinib) Now FDA Approved - November 13, 2013

Ibrutinib Phase 2 Study Results in Patients with Mantle Cell Lymphoma 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 of a Phase 2 study evaluating the investigational oral Bruton's tyrosine kinase (BTK) inhibitor ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) online. These data suggested ibrutinib may be effective and generally well-tolerated in patients with relapsed/refractory MCL.
Results of a separate study examining the safety and efficacy of ibrutinib monotherapy for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), some of whom had deletion of part of chromosome 17 (del 17p), has also been published online by The NEJM. Pharmacyclics sponsored both studies and is jointly developing ibrutinib with Janssen Research & Development, LLC.
"There remains a significant unmet need for patients with MCL," said lead author Michael Wang, M.D., Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center. "These data are exciting because they demonstrate that the longer MCL patients are treated with ibrutinib the better they respond to the treatment."
The study evaluated 111 patients with relapsed/refractory MCL treated with ibrutinib. The majority of patients (86 percent) had intermediate or high-risk MCL and had previously undergone treatment with a median of three prior therapies before enrollment in the study. Patients were enrolled in two cohorts based on whether they had prior exposure to bortezomib. Overall response rate across both cohorts was 68 percent with 47 percent of patients achieving a partial response and 21 percent achieving a complete response where all signs of cancer are gone. The estimated median response duration was 17.5 months. The median progression free survival was 13.9 months and while the median overall survival for this study has not yet been reached it is estimated to be 58 percent at 18 months. The overall response to ibrutinib was independent of prior treatment including bortezomib and lenalidomide or underlying risk/prognosis, bulky disease, gender or age. In an initial subset of patients enrolled in the study who have the longest follow up (n=51), the response to ibrutinib increased with longer duration of treatment, with the complete response rate increasing from 16 percent at a median follow-up of 3.7 months to 37 percent at a median follow-up of 18.2 months.
The majority of adverse events (AEs) were Grade 1 or 2 in severity, with the most common AEs attributed to ibrutinib being diarrhea, infections and fatigue. Only 7 percent of patients irrespective of relationship experienced an AE leading to treatment discontinuation. Grade 3-4 hematological toxicities were infrequent, with neutropenia (16 percent), thrombocytopenia (11 percent) and anemia (10 percent) as the most frequent hematological AEs reported.
Data from this study were presented at the annual meeting of the American Society of Hematology in December 2012, the European Hematology Association annual meeting in June 2013 and are being presented at the 12th International Conference on Malignant Lymphoma in Lugano, Switzerland this week.
Study Design
The Phase 2, open-label, multicenter study was designed to determine the safety and efficacy of ibrutinib in patients with relapsed or refractory MCL. The primary endpoint of the study was overall response rate. Secondary endpoints included: duration of response, progression free survival, overall survival and frequency and severity of adverse events.
The study enrolled patients with a confirmed diagnosis of relapsed or refractory MCL at 18 sites internationally, and 86 percent of patients had intermediate or high-risk MCL. Study participants received a 560mg daily oral dose of ibrutinib monotherapy and were treated into two cohorts based on prior exposure to bortezomib — either no prior bortezomib (n=63) or prior bortezomib (n=48). Overall, patients had received a median of three prior therapies.
About Mantle Cell Lymphoma
MCL, a B-cell malignancy, is an aggressive type of B-cell non-Hodgkin lymphoma (NHL) that usually occurs in older adults. The disease typically begins in the lymph nodes but can spread to other tissues, such as bone marrow and liver. Ibrutinib targets the B-cell receptor pathway an important pathway in malignant B-cell growth and proliferation. In the United States there are approximately 5,000 new cases of MCL each year.
About Ibrutinib
Ibrutinib was designed to specifically target and selectively inhibit an enzyme called Bruton tyrosine kinase (BTK). BTK is a key mediator of at least three critical B-cell pro-survival mechanisms occurring in parallel —regulation of apoptosis, cell adhesion, and cell migration and homing.
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, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Waldenstrom's macroglobulinemia and multiple myeloma. To date six Phase 3 trials have been initiated with ibrutinib and a total of 30 trials are currently registered on www.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 with 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, 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 transition report on Form 10-K for the six month period ended December 31, 2012 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
SVP of Investor Relations and Corporate Communications
Phone: 408-215-3325
U.S. Medical Information, Pharmacyclics:
855-ibrutinib [(855) 427-8846]
SOURCE Pharmacyclics, Inc.
 

Posted: June 2013

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