The FDA granted accelerated approval to AstraZeneca and Acerta Pharma's acalabrutinib for mantle cell lymphoma, a second approval for the BTK inhibitor class. The agency approved AbbVie and Janssen's first-in-class BTK inhibitor, ibrutinib, in 2013 for the same indication. Ibrutinib has since picked up supplementary approvals in a few settings, including chronic lymphocytic leukaemia and graft-versus-host disease.

The BTK kinase acts downstream of B cell receptor signalling, and is implicated in the activation of several cell-survival pathways that are often co-opted by lymphoid malignancies (Nat. Rev. Drug Discov. 12, 229–243; 2013).

In a 124-patient pivotal trial of acalabrutinib in mantle cell lymphoma, AstraZeneca and Acerta showed that second-line use of their drug resulted in complete or partial responses in 80% of patients.

Ibrutinib currently earns more than US$2.8 billion per year in annual global sales, and analysts forecast it could reach close to $9.5 billion by 2021. Analysts forecast sales of just over $1 billion for the newly approved acalabrutinib by 2022, according to the Cortellis database from Clarivate Analytics. BeiGene is also vying for a slice of this oncology market, with its phase III candidate BGB-3111.

But drug developers are also increasingly interested in the potential for BTK inhibitors in autoimmune conditions, because the kinase plays a key role in B cell maturation, differentiation and proliferation. AstraZeneca's acalabrutinib, Bristol-Myers Squibb's BMS-986142, Eli Lilly's LY333764, Merck KGaA's evobrutinib and Roche's RG7845 are all in phase II development for rheumatoid arthritis. Merck and Roche are testing their candidates in phase II trials for lupus. Merck is trialling its drug in multiple sclerosis. And in November, Sanofi partnered with Principia Biopharma in a $765 million biodollar deal to develop the phase I BTK inhibitor PRN2246 for multiple sclerosis.