AbbVie’s filgotinib opt-in could be a no-brainer

AbbVie will shortly receive the final 24-week data from the Darwin-2 study of Galapagos’s filgotinib in rheumatoid arthritis, which is the trigger point for a decision on whether to license the Jak-1 inhibitor under the companies’ 2012 option-based deal.

However, given the strong efficacy data reported last week from the Darwin-1 study, also in RA, that decision – at least in terms of these phase II trial results – looks unlikely to be too taxing. Indeed, Galapagos’s probably partly-in-jest suggestion that it would be happy to waive the obligation to opt in that exists in certain circumstances suggests that the Belgian group thinks finding another partner, if that were required, would be easy.

But this also acknowledges that the opt-in decision by AbbVie could be complicated by external considerations, and will probably be determined more by the competitive environment for small-molecule RA projects than the clinical data per se. AbbVie is obliged to complete the deal if filgotinib meets certain undisclosed efficacy criteria in the two Darwin studies, and has the option to do so if these criteria are not met.

Meeting the criteria 

Galapagos intimated that its 24-week Darwin-1 data met the licensing requirement – and indeed, the results were so good that it would be surprising if they had not. The Darwin-1 study tested seven different doses of filgotinib, a mix of once and twice daily, as an add-on to methotrexate (MTX) in patients with moderate to severely active RA and inadequate response to MTX over 24 weeks.

Darwin-1 showed statistically significant improvements in ARC20 scores at the two higher doses tested. In terms of ACR50 and ACR70 it achieved significance at all doses tested, some to high levels. Darwin-2 tests three once-daily doses of filgotinib as monotherapy in patients with moderately to severely active RA, who had an inadequate response to MTX alone. Interim data at 12 weeks from this study were published in April.

Results of filgotinib studies
Once-daily dosing Twice-daily dosing
50mg 100mg 200mg 25mg 50mg 100mg
Darwin-1 24-week placebo-adjusted scores 
ACR20, % 13 18 31*** 14 18 38***
ACR50, % 18* 29*** 33*** 18* 18* 33***
ACR70, % 13* 24** 20** 12* 15** 30***
Darwin-2  12-week interim data   
ACR20, % 36*** 35*** 42***
ACR50, % 25** 23** 33***
ACR70, % 4 15* 9
*p<0.05 vs placebo; **p<0.01 vs placebo; ***p<0.001 vs placebo

Filgotinib would presumably be the third Jak inhibitor to reach the market for RA, some three years after Lilly’s Jak-1/2 inhibitor baricitinib, which has completed two phase III studies and has two remaining phase III trials left to report over the coming months (Key data for the last few oral antirheumatics, July 24, 2015).

The 24-week Darwin-1 data suggest that filgotinib has a stronger efficacy than baricitinib as well as the approved 5mg twice-daily dose of Pfizer’s Xeljanz with a best-in-class safety profile. But competition in small-molecule drugs for RA could be fierce and the risks are highlighted by the lacklustre performance of Xeljanz, which despite a huge R&D investment has not lived up to sales expectations since its 2012 launch.

Nevertheless, whether AbbVie opts in by virtue of the contractual obligation or by a positive decision by the 60-day deadline from receiving full data, it would have to make an immediate payment of $200m to Galapagos, with further milestones totalling up to $1bn and royalties in the double-digit range. AbbVie would also have to make an R&D spending commitment for phase III studies of several hundred million dollars.

Competing internal candidate

The real issue for AbbVie is the presence of an internally-developed Jak-1/2 inhibitor, ABT-494, which has just completed two phase II trials, according to Clinicaltrials.gov. All things being equal, economics would favour the internal candidate, since there are no milestone and royalty obligations, but forgoing the filgotinib option would allow a competitor the opportunity to develop it and compete with ABT-494.  

Hence, analysts are speculating that if AbbVie exercises the option and develops filgotinib for RA it could re-position ABT-494 for oncology indications, as it would surely not want to abandon the project or license it to a third party. In these circumstances ABT-494 would compete with the Novartis/Incyte's Jak-1/2 inhibitor Jakafi, which is approved for polycythaemia vera and myelofibrosis and in phase III development for pancreatic cancer.

Whatever the outcome of AbbVie's deliberations investors will not have to wait long, as it is understood that the group must render a decision by the end of September. 

To contact the writer of this story email Robin Davison in London at robind@epvantage.com or follow @RobinDavison2 on Twitter

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