New Drug Application Filed for Ibrutinib in Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma

Staff Writer
Published Online: July 10, 2013
Blood Cells




The FDA has received a new drug application for ibrutinib as a therapy for previously treated chronic lymphocytic leukemia (CLL) and previously treated mantle cell lymphoma (MCL). The new drug application comes after high response rates observed in two clinical trials published last month.

Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor, and if approved, would be the first to receive approval from the FDA. Bruton’s tyrosine kinase is associated with apoptosis, cell adhesion, cell migration, and other cellular processes that can help a tumor survive. Ibrutinib appears to selectively target the implicated enzyme while sparing healthy T cells. The drug is being investigated in multiple hematologic malignancies, including multiple myeloma, follicular lymphoma, and diffuse large B-cell lymphoma.

The announcement of the filing was made by Janssen Research and Development, LLC, and if approved, the drug would be co-commercialized in the United States by Janssen Biotech, Inc. and Pharmacyclics.

“The FDA submission is another important milestone for ibrutinib since we formed our strategic partnership with Pharmacyclics just 18 months ago,” said Peter F. Lebowitz, MD, PhD, Global Oncology Head at Janssen, in a statement. “Both companies recognize that there is great unmet need among these patient populations, and together in close collaboration with the FDA, as part of its Breakthrough Therapy Designation pathway, we have been able to accelerate the ibrutinib development program for the benefit of patients.”

The filing for the indication for CLL was based on the results of a phase Ib/II trial, in which 85 patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) received ibrutinib orally once daily, with 51 patients receiving a 420 mg dose and 34 patients receiving an 840 mg dose.1

The overall response rate (ORR) in both treatment groups was 71%, with an additional 20% of patients in the 420 mg dose arm and 15% of patients in the 840 mg dose arm experiencing a partial response with lymphocytosis. After 26 months of follow-up, the estimated rate of progression-free survival (PFS) was 75%, and the rate of overall survival (OS) was 83% for all patients, irrespective of the dose. Side effects were minimal and consisted mostly of grade 1 or 2 transient diarrhea, fatigue, and upper respiratory tract infection.

In the study that looked at patients with MCL, 111 patients with relapsed or refractory disease received a daily dose of 560 mg of ibrutinib. Patients enrolled in this phase II trial were divided into two groups: those who had received ≥2 complete cycles of prior bortezomib therapy and patients who had received <2 complete cycles of the therapy, including those with no prior bortezomib therapy. ORR was the primary endpoint, with duration of response, PFS, OS, and safety serving as secondary endpoints.2

Related Articles
Jennifer Woyach, MD, assistant professor of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, discusses the association of disease progression on ibrutinib therapy with the acquisition of resistance mutations as seen at The Ohio State University Comprehensive Cancer Center.
Kenneth R. Carson, MD, assistant professor, Division of Oncology, Washington University, discusses post-therapy imaging in lymphoma.
John C. Byrd, MD, a professor of Medicine at The Ohio State University Comprehensive Cancer Center, discusses updates in the treatment of CLL.
JTT Articles
Manageable Safety Profile Determined in BOLERO-3
Novel Treatment Options for T790M-Mutant Non-Small Cell Lung Cancer
The Transformation of Treatment in CLL: A Q & A With Dr. William G. Wierda
External Resources

AJMC
HCPLive
OncLive
PainLive
Pharmacy Times
Physicians' Education Resource
Physician's Money Digest
Internal Resources

Articles
Fellows
Publications
Targeted Communications
Resources
Connect With Us:

About Us
Advertise
Contact Us
Privacy Policy
Terms & Conditions
Intellisphere, LLC
666 Plainsboro Road
Building 300
Plainsboro, NJ 08536
P: 609-716-7777
F: 609-716-4747

Copyright TargetedOnc 2013
Intellisphere, LLC. All Rights Reserved.