AbbVie to advance development of ABT-494 for rheumatoid arthritis, return filgotinib rights to Galapagos

AbbVie announced Friday that following positive data from the Phase IIb BALANCE-I and BALANCE-II trials, it will move its experimental JAK1 inhibitor ABT-494 into Phase III development in rheumatoid arthritis by year's end with a once-daily formulation. The company noted that as a result it has decided against exercising its right to in-license Galapagos' JAK1 inhibitor filgotinib. "We believe ABT-494 has the potential to become a best-in-class therapy for patients," commented Michael Severino, chief scientific officer at AbbVie, adding "in our view, ABT-494 also offers a faster path to Phase III development with less uncertainty."

The BALANCE-I study evaluated one of four twice-daily doses of ABT-494 against placebo in 276 adults with moderate-to-severe rheumatoid arthritis who had an inadequate response or intolerance to anti-TNF biologic therapy. AbbVie noted that roughly 30 percent of the patients had inadequately responded to at least two anti-TNF agents, while 20 percent had an insufficient response to treatment with a non-TNF biologic. Meanwhile, in the placebo-controlled BALANCE-II trial, 300 adults with moderate-to-severe rheumatoid arthritis who had a poor response to methotrexate were treated with one of five doses of ABT-494, with all administered twice daily, except for the highest 24-mg dose, which was given once a day. In both studies, the primary endpoint was the proportion of patients achieving an ACR20 response at week 12, while secondary endpoints included safety and tolerability measures, in addition to the proportion of patients with ACR50 and ACR70 responses.

Results from BALANCE-I demonstrated that all four active treatment arms had met the primary endpoint of ACR20 response, with rates ranging from 56 percent to 73 percent, versus 35 percent for placebo. In the BALANCE-II study, the primary endpoint was also achieved for all except the lowest dose, with ACR20 rates as high as 82 percent among ABT-494-treated patients, compared with 50 percent for placebo.

Additionally, ACR50 and ACR70 responses of as great as 44 percent and 27 percent, respectively, were observed among patients in the ABT-494 arms in BALANCE-I, compared to 17 percent and 4 percent in the respective placebo groups. In BALANCE-II, ACR50 and ACR70 rates were as high as 50 percent and 31 percent, respectively, versus 20 percent and 7 percent for placebo. AbbVie stated that the overall rates of discontinuation and adverse events across both studies were less than 5 percent and less than 3 percent, respectively. The drugmaker noted that a Phase II study of the JAK1 inhibitor in the treatment of Crohn's disease is currently ongoing.

Meanwhile, analysts estimated that AbbVie could save about $1 billion in royalty payments based on its decision to opt-out of its collaboration with Galapagos on filgotinib. Commenting on the news, Morgan Stanley analyst Matthew Harrison said "Galapagos management can negotiate another deal with a key rheumatoid arthritis player and advance [filgotinib] quickly." Shares in Galapagos fell as much as 27 percent on news of AbbVie's decision.

For related analysis, see ViewPoints: JAK inhibitor up for grabs as AbbVie turns its back on Galapagos compound.

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