AbbVie said today it will advance ABT-494, its own internally-developed selective JAK1 inhibitor, to Phase III studies in rheumatoid arthritis rather than license the JAK1 inhibitor filgotinib (GLP0634) from Galapagos–which responded with its own plans to advance fligotinib into Phase III.
AbbVie said that it will return all rights to the compound to Galapagos, citing promising results in a pair of Phase II studies of ABT-494.
“In our view, ABT-494 also offers a faster path to Phase III development with less uncertainty,” Michael Severino, M.D., AbbVie evp, research and development and CSO, said in a statement. “We believe ABT-494 has the potential to become a best-in-class therapy for patients.”
In a separate statement, AbbVie said ABT-494 met its primary endpoint of at least a 20% improvement as defined by the American College of Rheumatology (ACR20) after 12 weeks of treatment in the BALANCE-I and BALANCE-II clinical trials. The ACR20 response was achieved across all dose levels, except the lowest dose in BALANCE-II, the company added.
BALANCE-I enrolled 276 patients, approximately 30% of whom had an inadequate response to two or more anti-TNF agents and 20% had an inadequate response to treatment with a non-TNF biologic. BALANCE-II enrolled 300 patients with an inadequate response to prior treatment with methotrexate (MTX).
In BALANCE-I, 73% of patients showed ACR20 response, while 44% of patients showed at least a 50% improvement (ACR50). In BALANCE-2, ACR20 response climbed to 82%, with 50% of patients achieving ACR50, AbbVie said.
AbbVie backed out of its filgotinib collaboration more than a month after Galapagos published results from its DARWIN I Phase IIb trial. In a statement today, Galapagos cited ACR20 responses ranging from 61% at 50mg once-daily to 87% at 100mg, twice-daily. ACR50 responses ranged from 35% at 50mg once-daily to 62% at 100mg twice-daily. Galapagos cited promising results from DARWIN 2 last month, with the highest ACR20 response being 77% at the 100mg once-daily dose and the highest ACR50 response, 45% at the 200mg once-daily dose.
“Galapagos is currently in advanced discussions with a substantial number of large pharma companies to partner filgotinib,” said Onno van de Stolpe, CEO of Galapagos, in a statement. “We anticipate starting Phase III in rheumatoid arthritis with filgotinib early in 2016.”
AbbVie spun out in 2013 from Abbott, which a year earlier gained rights to develop and commercialize fligotinib under a collaboration that could have generated $1.35 billion plus royalties for Galapagos.
At the time, AbbVie paid Galapagos $150 million upfront and agreed to a one-time $200 million fee were it to license the program following Phase II studies, if the studies meet certain pre-agreed criteria. The deal also included $1 billion in potential payments to clinical and regulatory milestones, plus tiered double-digit royalties on net sales upon commercialization.
The following year, AbbVie and Galapagos extended their collaboration beyond rheumatoid arthritis to include Crohn's disease as well.
“We are expecting data from our Phase 2B FITZROY study with filgotinib in Crohn's disease by yearend,” van de Stolpe added.