FISHing for success

New leukemia CDx deal unites Abbott, Janssen, Pharmacyclics

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ABBOTT PARK, Ill.—A new collaboration has been struckbetween Abbott, Janssen Biotech Inc. and Pharmacyclics Inc., in which thepartners will investigate the potential of Abbott's proprietary fluorescence in-situ hybridization (FISH) technologyfor the development of a molecular companion diagnostic test to identifypatients with a genetic subtype of chronic lymphocytic leukemia (CLL), the mostcommon form of adult leukemia.
Per the terms of the agreement, Abbott will develop aFISH-based test to identify high-risk CLL patients who may present with adeletion in chromosome 17p (del17p) and might respond favorably to ibrutinib,an oral, small-molecule inhibitor of Bruton tyrosine kinase (BTK). Patientswith a deletion on chromosome 17p typically respond poorly tochemoimmunotherapy and have few treatment options.
Abbott's Vysis CLL FISH Probe Kit, which targets multiplegenes within the del17p region and is used to help determine prognosis for CLLpatients, will be leveraged for investigational use only to determine geneticmarker status as part of the collaboration. Abbott received U.S. Food and DrugAdministration (FDA) clearance for the kit in 2011.
"Like Abbott's other collaborations in the area of companiondiagnostics, our goal is to leverage molecular technologies to help ensure thatthe right medicine is getting to the right person," John Coulter, vicepresident of molecular diagnostics at Abbott, said in a press release. "Canceris a complex disease where, historically, therapies have demonstrated only a25-percent efficacy rate. Companion diagnostic tests can help improve theseoutcomes by selecting patients that are more likely to respond to specifictherapies, reducing time to the most effective treatment and increasing thenumber of positive outcomes."
Janssen and Pharmacyclics are currently developing ibrutinibfor the treatment of several B-cell malignancies. The two companies establisheda collaborative development and worldwide license agreement for ibrutinib,originally known as PCI-32765, in December 2011, when they agreed to jointlydevelop 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 makeadditional payments if certain development and regulatory milestones areachieved.
BTK is an important cell-signaling enzyme found inhematopoietic cells, including B-cells. In the body, B-cell activation isdriven by the B-cell receptor (BCR), and BTK plays a significant role in theBCR 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 inpreclinical models, this resulted in an inhibition of proliferation, adisruption of tumor-cell adhesion and apoptosis (cell death) in malignantB-cells," Pharmacyclics notes on its website.
In mouse studies, ibrutinib was found to also reduce thelevels of circulating autoantibodies and reverse the course of arthritis, whichmeans the compound could have potential in autoimmune and inflammatorydisorders as well. The compound is currently being developed in B-cellmalignancies 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 FDAas a monotherapy for two B-cell malignancies: in patients with relapsed orrefractory MCL who have received prior therapy, and for patients withWaldenström's macroglobulinemia, a rare type of lymphoma. Current plans arethat the filing for ibrutinib in MCL will be made prior to the end of thisyear.
"As an oncology product, ibrutinib receiving theBreakthrough Therapy Designation is an example of progress and hope forpatients fighting a range of cancers. This designation shows that the FDA isdedicated to using an 'all hands on deck approach' to work on products thatshow promise in treating serious and life-threatening diseases," Dr. EllenSigal, chair and founder of Friends of Cancer Research, said in a press releaseabout the FDA's decisions.

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