FISHing for success
ABBOTT PARK, Ill.—A new collaboration has been struck between Abbott, Janssen Biotech Inc. and Pharmacyclics Inc., in which the partners will investigate the potential of Abbott's proprietary fluorescence in-situ hybridization (FISH) technology for the development of a molecular companion diagnostic test to identify patients with a genetic subtype of chronic lymphocytic leukemia (CLL), the most common form of adult leukemia.
Per the terms of the agreement, Abbott will develop a FISH-based test to identify high-risk CLL patients who may present with a deletion in chromosome 17p (del17p) and might respond favorably to ibrutinib, an oral, small-molecule inhibitor of Bruton tyrosine kinase (BTK). Patients with a deletion on chromosome 17p typically respond poorly to chemoimmunotherapy and have few treatment options.
Abbott's Vysis CLL FISH Probe Kit, which targets multiple genes within the del17p region and is used to help determine prognosis for CLL patients, will be leveraged for investigational use only to determine genetic marker status as part of the collaboration. Abbott received U.S. Food and Drug Administration (FDA) clearance for the kit in 2011.
"Like Abbott's other collaborations in the area of companion diagnostics, our goal is to leverage molecular technologies to help ensure that the right medicine is getting to the right person," John Coulter, vice president of molecular diagnostics at Abbott, said in a press release. "Cancer is a complex disease where, historically, therapies have demonstrated only a 25-percent efficacy rate. Companion diagnostic tests can help improve these outcomes by selecting patients that are more likely to respond to specific therapies, reducing time to the most effective treatment and increasing the number of positive outcomes."
Janssen and Pharmacyclics are currently developing ibrutinib for the treatment of several B-cell malignancies. The two companies established a collaborative development and worldwide license agreement for ibrutinib, originally known as PCI-32765, in December 2011, when they agreed to jointly develop and market the compound. The deal is a 50/50 profit-loss agreement, with the companies sharing development and commercialization activities. Janssen paid $150 million up front as part of the agreement, and will make additional payments if certain development and regulatory milestones are achieved.
BTK is an important cell-signaling enzyme found in hematopoietic cells, including B-cells. In the body, B-cell activation is driven by the B-cell receptor (BCR), and BTK plays a significant role in the BCR signaling pathway.
"BCR signaling is thought to promote cell proliferation, adhesion and survival in many types of B-cell malignancies (cancers). Inhibitors of BTK … act downstream of the BCR and block BTK activity, and in preclinical models, this resulted in an inhibition of proliferation, a disruption of tumor-cell adhesion and apoptosis (cell death) in malignant B-cells," Pharmacyclics notes on its website.
In mouse studies, ibrutinib was found to also reduce the levels of circulating autoantibodies and reverse the course of arthritis, which means the compound could have potential in autoimmune and inflammatory disorders as well. The compound is currently being developed in B-cell malignancies such as CLL, small lymphocytic lymphoma, mantle cell lymphoma (MCL), diffuse large B-cell lymphoma and multiple myeloma.
Pharmacyclics and Janssen both issued announcements on Feb. 12 that ibrutinib had received Breakthrough Therapy Designations from the FDA as a monotherapy for two B-cell malignancies: in patients with relapsed or refractory MCL who have received prior therapy, and for patients with Waldenström's macroglobulinemia, a rare type of lymphoma. Current plans are that the filing for ibrutinib in MCL will be made prior to the end of this year.
"As an oncology product, ibrutinib receiving the Breakthrough Therapy Designation is an example of progress and hope for patients fighting a range of cancers. This designation shows that the FDA is dedicated to using an 'all hands on deck approach' to work on products that show promise in treating serious and life-threatening diseases," Dr. Ellen Sigal, chair and founder of Friends of Cancer Research, said in a press release about the FDA's decisions.