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.
