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When the US Food and Drug Administration approved Pharmacyclics' Bruton tyrosine kinase (BTK) inhibitor ibrutinib in November 2013, just 3 short years after it had entered into clinical testing, it was clear the small molecule was destined for a big future. AbbVie's purchase of Pharmacyclics for US$21 billion — providing rights to just one-half of the sales from the drug, which Pharmacyclics splits with Johnson & Johnson — shows that expectations for the first-in-class BTK inhibitor are still sky-high.

The drug is currently only approved for chronic lymphocytic leukaemia and for two rare blood cancers. But mid- and late-stage trials are testing the drug in other potentially profitable oncology indications, including non-Hodgkin lymphomas, multiple myeloma and acute myelogenous leukaemia. AbbVie aims to explore combinations to further expand ibrutinib's reach, potentially including the combination of ibrutinib plus AbbVie's Phase III B-cell lymphoma 2 (BCL-2) inhibitor, ABT-199 (go.nature.com/71T9kS). The BTK inhibitor may also act synergistically with immunotherapeutics to offer efficacy in solid cancers like breast cancer (Proc. Natl Acad. Sci. USA 112, E966–E972; 2015).

A few other companies are also developing BTK inhibitors for oncology indications. Acerta's ACP-196 is in Phase II trials for pancreatic cancer and in Phase I/II trials for lymphomas. Celgene's CC-292 is in Phase I trials for lymphomas. Gilead's GS-4059 is in Phase I trials for haematologic cancers.

Beyond oncology, Acerta and Celgene are developing their BTK inhibitors for rheumatoid arthritis (in Phase II trials). Pharmacyclics also has an ongoing trial of ibrutinib in a Phase I/II trial for graft-versus-host disease, and Merck KGaA has a BTK inhibitor in Phase I trials for autoimmune disorders.

Pharmacyclics also has a histone deacetylase (HDAC) inhibitor (see also Nature Rev. Drug Discov. 14, 225–226; 2015) and a factor VIIa inhibitor in Phase I/II oncology trials.