Discovering a transformative cancer drug: the case of ibrutinib.

Transformative medicines have extended and improved many lives. Few studies, however, have qualitatively investigated how transformative drugs are discovered and developed. We conducted semi-structured interviews to investigate how scientists discovered ibrutinib (Imbruvica), a transformative drug for chronic lymphocytic leukemia. Ibrutinib originated as a tool compound, created to help chemists understand the effects of inhibiting Bruton tyrosine kinase to treat autoimmune diseases. After the corporate owner of ibrutinib sold it to a struggling biotech firm for very little money, the biotech reconceptualized ibrutinib as a cancer therapy. Even after ibrutinib showed preliminary signs of efficacy, internationally accepted response criteria that did not account for its novel mechanism of action threatened to derail its development and ability to reach patients.