History
Ibrutinib was created by scientists at Celera Genomics as a tool compound for studying BTK function; it covalently binds its target — a feature ideal for a reagent, though generally not preferred in drug design.[17]
In 2006, in the course of acquiring an HDAC-focused program from Celera after its own initial discovery program had failed, Pharmacyclics also picked up Celera's small molecule BTK inhibitor discovery program for $2M in cash and $1M in stock and named the tool compound PCI-32765.[17][18] In 2011 after the drug had completed Phase II trials, Johnson & Johnson and Pharmacyclics agreed to co-develop the drug, and J&J paid Pharmacyclics $150 million upfront and $825 million in milestones.[19] Pharmacyclics was acquired by AbbVie in May 2015, and Abbvie projected global sales of US$1 billion in 2016 and $5 billion in 2020.[20]
It was approved by the US Food and Drug Administration (FDA) in November 2013, for the treatment of mantle cell lymphoma.[21] In February 2014, the FDA expanded the approved use of ibrutinib to chronic lymphocytic leukemia (CLL).[22][23] It was approved for Waldenström's macroglobulinemia in 2015.[24][25]
In March 2015, Pharmacyclics and AbbVie agreed that Abbvie would acquire Pharmacyclics for $21 billion;[26] the deal was completed that May.[27]
In March 2016, a new indication for ibrutinib was approved in the United States for patients with chronic lymphocytic leukemia (CLL).[28]
In May 2016, a new indication for ibrutinib was approved in the United States for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).[29]
In January 2017, a new indication for ibrutinib was approved in the United States for the treatment of adults with relapsed/refractory (R/R) marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.[30]
In August 2017, the FDA approved a new indication for ibrutinib to treat graft-versus-host disease. It was the first FDA-approved treatment for graft-versus-host disease.[31][32][33]
In February 2018, a tablet formulation of ibrutinib was approved for use in the United States.[34]
In August 2018, ibrutinib in combination with rituximab was approved in the United States for the treatment of adults with Waldenström's macroglobulinemia (WM), a rare and incurable type of non-Hodgkin's lymphoma (NHL).[35]
In January 2019, ibrutinib in combination with obinutuzumab was approved for the treatment of adults with previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).[36]
In April 2020, the FDA expanded the indication of ibrutinib to include its combination with rituximab for the initial treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).[37] Approval was based on the E1912 trial (NCT02048813), a 2:1 randomized, multicenter, open-label, actively controlled trial of ibrutinib with rituximab compared to fludarabine, cyclophosphamide, and rituximab (FCR) in 529 adult subjects 70 years or younger with previously untreated CLL or SLL requiring systemic therapy.[37]
