Earlier today, Abbott, Janssen Biotech and Pharmacyclics announced that they will collaborate in 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.

The new companion test will be based on Abbott’s proprietary fluorescence in situ hybridization (FISH) technology. With the FISH technology, researchers can identify whether too many, or too few, copies of a particular gene are present in the body’s cells or whether certain genes have rearrangements that play an active role in disease progression. Since the technology works especially well for identifying genetic markers in solid tumors, cancer diagnostics are one of the fastest growing applications.

FISH technology
Under the agreement, Abbott will develop a FISH-based test to identify high-risk CLL patients who have a deletion within a specific chromosome (chromosome 17p (del17p)) and may respond to Ibrutinib (PCI-32765), a selective, irreversible small molecule inhibitor of Bruton’s tyrosine kinase (BTK), a critical signaling kinase in the B-cell receptor pathway for tumor cell survival and proliferation.

Ibrutinib, a first-in-class oral therapy,is currently in development by Janssen and Pharmacyclics for several B-cell malignancies, including chronic leukemia and lymphoma. Patients harboring a deletion within chromosome 17p are poor responders to chemoimmunotherapy and have limited treatment options. Having a test that is able to accurately detect the 17p deletion identifies a specific patient population with a high unmet medical need.

Getting the right medicine to the right person
“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,” said John Coulter, vice president, Molecular Diagnostics, Abbott. “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.”

According to the American Society of Clinical Oncology (ASCO), future cancer therapies will be developed through molecular approaches that can accelerate development of more effective, personalized treatments. Identifying specific genetic characteristics of malignancies is expected to also support development of new treatments that target specific proteins involved in the development and growth of cancer.

In 2011, U.S. Food and Drug Administration approved Vysis CLL FISH Probe Kit. The kit targets multiple genes, including TP53 (tumor protein p53 gene, located on chromosome 17p) within the del17p region, and is used as an aid for determining prognosis for patients with CLL. Abbott’s Vysis CLL FISH Probe Kit will be used for investigational use only to determine genetic marker status as part of the co-development efforts between Janssen, Pharmacyclics and Abbott.

Breakthrough Therapy Designations
Pharmacyclics is conducting multiple trials evaluating ibrutinib as monotherapy and in combination with other anticancer agents and chemotherapies.

Earlier this year, the U.S. FDA granted Breakthrough Therapy Designations for ibrutinib as a monotherapy for two B-cell malignancies, including patients with relapsed or refractory mantle cell lymphoma (MCL) who have received prior therapy, and in patients with Waldenstrom’s macroglobulinemia (WM).

Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), Breakthrough Therapy Designation is intended to expedite the development and review time for a potential new medicine “to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.”[1]

“The Breakthrough Therapy Designations for ibrutinib represents a major leap forward in accelerating drug development timelines,” noted Paul Stoffels, M.D., Chief Scientific Officer and Worldwide Chairman, Pharmaceuticals, Johnson & Johnson. “We’re working with Pharmacyclics and the FDA to ensure the clinical development program for ibrutinib continues to move forward as quickly as possible.”

“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,” said Dr. Ellen Sigal, Chair and Founder of Friends of Cancer Research, a think tank and advocacy organization based in Washington DC. “The breakthrough pathway that our organization worked to create is intended to speed up the development and review of treatments that may demonstrate substantial improvement over existing therapies, and ibrutinib is a great example of using this new designation to potentially accelerate patient access to promising treatments.”

References
[1] PUBLIC LAW 112?144?JULY 9, 2012. U.S. Government Printing Office.

Clinical trials:
NCT00849654 – Study of the Safety and Tolerability of PCI-32765 in Patients With Recurrent B Cell Lymphoma (PCYC-04753)
NCT01578707 – A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (RESONATE?)

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