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Therapeutics for Rare and Neglected Diseases

Auranofin for Chronic Lymphocytic Leukemia

Approximately 15,000 people in the United States are diagnosed each year with a rare blood cancer called chronic lymphocytic leukemia (CLL). Patients ultimately become resistant to current chemotherapies, and their disease recurs — leading to death. Working with the NCATS Chemical Genomics Center, the lead investigator found that the drug auranofin selectively kills CLL cells. Auranofin was previously approved by the Food and Drug Administration (FDA) as a treatment for rheumatoid arthritis. The goals of this TRND project are to develop auranofin as a treatment for refractory CLL and to develop a novel collaborative paradigm that is broadly applicable to repurposing drugs for rare diseases.

Scientific Synopsis

The Institute for Advancing Medical Innovation at the University of Kansas, the Leukemia & Lymphoma Society (LLS), and the NCATS TRND program have formed a collaboration known as The Learning Collaborative (TLC). The goal of this collaboration is to identify new drug therapies for patients with rare blood cancers such as CLL. CLL is a blood and bone marrow disease that usually occurs in middle-aged adults and progresses over a long period. Currently, therapeutic options for CLL patients are limited and few therapies are under development. There is an important need for new medical treatments.

To find compounds that selectively kill CLL cells versus normal donor lymphocytes, TLC carried out a high-throughput screen of a library of known drugs using a cell proliferation assay. The arthritis drug auranofin was identified as a potent, selective cytotoxic agent. A cooperative research and development agreement (CRADA) has been established to conduct the necessary pre-clinical and clinical proof-of-concept studies to determine the potential benefit of auranofin in treating individuals with relapsed CLL. The development strategy for repurposing the therapeutic use of auranofin for CLL capitalizes on available pre-clinical and clinical experience with a known, previously approved, therapeutic drug to accelerate clinical testing of the same drug for a new medical indication (CLL). The goal is to complete pre-clinical through clinical trial studies, at which time an industry partner will be engaged.

Lead Collaborator

University of Kansas Medical Center, Kansas City

Scott Weir, Pharm.D., Ph.D.

Public Health Impact

Approximately 15,000 people in the United States are diagnosed with CLL each year. Currently, CLL is treated with various chemotherapies, but patients eventually become resistant to this treatment and can die as a result. There is an unmet medical need to develop novel therapies for chemotherapy-resistant disease. In addition, whereas traditional chemotherapy can be quite toxic, auranofin has received previous regulatory approval and was demonstrated to be reasonably safe and effective in the treatment of arthritis.

Outcomes

A unique collaboration called The Learning Collaborative (TLC) was established among TRND, the University of Kansas, and the nonprofit Leukemia & Lymphoma Society. Each organization has contributed expertise and funding to the development of auranofin for CLL. The team completed all pre-clinical studies necessary to support an Investigational New Drug (IND) application to the FDA in less than a year after initiation of the auranofin collaboration. The IND was cleared by the FDA, and auranofin underwent Phase I–IIa clinical trials in patients at three sites (NIH, the University of Kansas and Ohio State University). In the past several months, four quite promising new treatments for CLL have been introduced. As such, the perceived unmet medical need for this blood cancer is much less than when the TLC team embarked on this project. As a partnership, TLC has decided to close the ongoing CLL clinical trial evaluating auranofin. The TRND/TLC project now is concluded.

Last updated: 09-06-2017
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