In September 2015, when Galapagos NV lost its partnership with Abbvie Inc. for Janus kinase (JAK) 1 inhibitor filgotinib in rheumatoid arthritis (RA) – but kept intact their agreement for cystic fibrosis (CF) – the search for a new tie-up began right away, even as the spurning entity moved ahead with its own late-stage, oral JAK1 candidate in RA, ABT-494.
Abbvie needed to move fast, with biosimilar versions of Abbvie's blockbuster Humira (adalimumab) expected by 2020 or before. Three months after the North Chicago firm declined to exercise its in-license option for filgotinib, Mechelen, Belgium-based Galapagos landed a deal with Gilead Sciences Inc., of Foster City, Calif., wherein the latter paid $300 million in cash, bought $425 million in shares, and pledged up to $1.35 billion more in potential milestone rewards. (See BioWorld Today, Sept. 28, 2015, and Dec. 18, 2015.)
By then, Abbvie already had a strong development lead. Tuesday, Galapagos and Gilead disclosed the start of their FINCH phase III program with filgotinib, which will be playing catch-up to ABT-494. FINCH 1 is a 52-week, randomized, placebo- and Humira-controlled study in combination with methotrexate (MTX) in an expected 1,650 patients who have had inadequate response to MTX.
The primary endpoint is the American College of Rheumatology measure of at least 20 percent symptom improvement (ACR20) at week 12. The study will also include radiographic assessment at weeks 24 and 52.
FINCH 2 is a 24-week, randomized, placebo-controlled study in an expected 423 patients who are on conventional disease-modifying anti-rheumatic drugs, and have had an inadequate response to biological treatment.
The primary endpoint is ACR20 at week 12. FINCH 3 is a 52-week, randomized study in an expected 1,200 MTX-naïve patients to study filgotinib in combination with MTX, as well as monotherapy. The primary endpoint is ACR20 at week 24. Researchers will also measure radiographic progression.
Meanwhile, the Abbvie/Galapagos tie-up in CF stands "squarely" in the headlights of investors, said Credit Suisse analyst Vamil Divan. "We are encouraged that the SAPHIRA phase II trial remains on track, with solid recruitment in six EU countries and Australia," he wrote in a research report June 16. There had been some frets that the availability of Kalydeco (ivacaftor, Vertex Pharmaceuticals Inc.) might affect enrollment, but it's apparently not happening.
"We are looking forward to topline phase II SAPHIRA results at North American Cystic Fibrosis Conference in October" in Orlando, Fla., he said. The experiment is testing GLPG1837, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator for class III mutations.
Specifically, SAPHIRA is examining the candidate's safety, tolerability, and efficacy in CF patients with a G551D (SAPHIRA 1) or S1251N (SAPHIRA 2) class III mutations. Galapagos is working with would-be correctors of mutations as well as potentiators, i.e., enhancers of CFTR activity when it's correctly located.
LILLY DATA BOOST FIRST-LINE OPTIMISM
Jefferies analyst Peter Welford opined in a report earlier this month that Galapagos and Abbvie "are likely lagging behind market incumbent Vertex, with a combo [study] planned in about the second half of this year, hence superior proof-of-concept in phase I/II [trials] may be critical to expedite pivotal trial enrollment and ultimately gain share." But he was enthusiastic about filgotinib in RA. "Impressive phase IIb DARWIN RA data support our confidence in $3.5 billion worldwide peak sales with partner Gilead, including $2.9 billion in RA and $600 million in Crohn's [disease], with the latter backed by positive phase II FITZROY data. We assume launch by about the second half of 2019," he wrote, estimating 20-30 percent tiered royalties. "Abbvie remains the most significant competitive threat, in our view," with ABT-494, he added. In late April 2015, Galapagos unveiled 12-week DARWIN data, raising hopes that Abbvie might take the in-license option when 24-week results rolled out later. (See BioWorld Today, April 29, 2015.)
Earlier the same month that Gilead inked the agreement for filgotinib, Galapagos popped the lid off positive phase II interim data in Crohn's disease via the FITZROY study. The experiment met the primary endpoint with a statistically significant (p=0.0067) clinical remission rate of 48 percent (n=128), vs. 23 percent for placebo (n=44). It was the first time a JAK inhibitor proved its efficacy in Crohn's.
During Galapagos' late July conference call on second-quarter earnings, analyst Michael Vlemmix with KBC Securities asked about JAK inhibitors' prospects as first-line, chronic therapy in RA. "The positioning and potential benefits versus the current [tumor necrosis factor (TNF) alpha drugs] are clear, but can you maybe elaborate a bit why you believe that JAK inhibitors will come before the interleukin-6 [IL-6] inhibitors?"
Chief financial officer Bart Filius rose to the challenge. "Obviously we're a couple of years out before we're actually starting to the commercial strategy, but I do believe that an oral drug has a meaningful benefit over the biologics, both the TNF and the IL-6," he said. "So, let's first see what the clinical outcomes are of the phase III trial. But I do think there is really a place for JAKs, and if you look at the results that Lilly has been showing with baricitinib, I think that's also clear both in terms of efficacy and safety, for the JAKs to go before the biologics, and as such go before TNFs as well as the IL-6 category."
Last fall, Indianapolis-based Eli Lilly and Co. and Incyte Corp., of Wilmington, Del., released topline phase III data with baricitinib in RA showing the oral JAK1/2 inhibitor beat Humira. (See BioWorld Today, Oct. 15, 2015.)