From no-go-tinib to now-go-tinib. Galapagos’s Jak inhibitor filgotinib looks worthy of attracting a new partner after positive interim phase II results in Crohn’s disease.
The Belgium-based company’s fortunes seem to be on the up again, less than three months after AbbVie pulled out of a deal in rheumatoid arthritis. While the latter is focusing on its own Jak-targeting agent, ABT-494, the likes of Johnson & Johnson and Sanofi could be interested in filgotinib, Bryan Garnier analysts believe.
Galapagos stock rose 16% at €51.86 in mid-afternoon trading today, not too far off its price before the AbbVie partnership collapsed.
Heading the Jak pack
Filgotinib looks especially attractive now as it is the most advanced Jak inhibitor in Crohn’s, after Pfizer recently shelved Xeljanz in the disorder. This gives filgotinib a lead on its rivals, including ABT-494, which is in the phase II Celest study with a primary completion date of December 2017.
Notably, Lilly and Incyte’s contender baricitinib, which recently reported promising results in RA, is not being developed in Crohn’s.
Galapagos is seeking a partner by the end of the year or in early 2016. A deal should also revive filgotinib in RA, where phase III trials are slated to begin in the first half of next year.
Meanwhile, the company can celebrate interim results from the 175-patient Fitzroy phase II study, which met its primary endpoint of clinical remission versus placebo at 10 weeks. Remission was defined as the percentage of patients achieving a Crohn’s disease activity index (CDAI) score of below 150.
|10-week interim results from Fitzroy phase II study|
|Clinical remission (CDAI lower than 150)||23%||48%||0.0067|
|Clinical response (CDAI decrease 100 points or more)||41%||60%||0.0386|
|Total IBDQ score, mean change from baseline||17.56||33.82||0.0045|
Jefferies analysts noted that the remission rate was “broadly similar” to those seen with existing Crohn’s drugs including Remicade, Humira, Cimzia and Tysabri, “impressive given Fitzroy included prior anti-TNF failures”.
They forecast overall peak sales of $3bn, with $250m coming in Crohn’s, but added that this could be conservative if the benefit seen in the study was maintained to week 20. Full 20-week results are due in the first half of next year.
While filgotinib already has an edge over other Jak inhibitors in terms of timing, it could also have clinical benefits in Crohn’s, some analysts believe.
Because it is selective for the Jak-1 receptor, and avoids Jak-2, it could sidestep the issue of decreased haemoglobin levels seen with Xeljanz, for example. ABT-494 has also been linked with a greater drop in haemoglobin versus filgotinib, albeit in RA trials – supporting Galapagos's claim that its project is more selective than AbbVie's.
This could help differentiate filgotinib in Crohn’s, where patients can become anaemic through losing blood in their stools. Haemoglobin, or more accurately haematocrit level, is a key measure on the CDAI.
Galapagos will be making the most of any advantage it might have in its quest to attract a partner as time is short. It will need a collaborator to fund the phase III RA trial, the design for which Galapagos intends to submit to the FDA in January.