Gilead and Galapagos have notched another series of late-stage wins for their JAK inhibitor filgotinib, with one analyst saying safety “looks clean” after recent scares in the class.
Here’s the breakdown of the data, which was split over two trials, FINCH 1 AND FINCH 3. In the latter, the pair were testing their drug in a phase 3 for 24 weeks in patients with moderately-to-severely active rheumatoid arthritis (RA).
Here, filgotinib was being tested as a combo with methotrexate (MTX) and as monotherapy in MTX-naïve patients.
The drug hit its primary endpoint, hitting the standard as seen as the American College of Rheumatology 20% response (ACR20) after six months, given that the proportion of patients hitting this was “significantly higher” for filgotinib 200 mg plus MTX and filgotinib 100 mg plus MTX compared with MTX alone.
But safety is still something of an overhang, to quote Jefferies, given the black box warnings and DVT/PE events that have overshadowed the class as a whole.
While analysts see these issues as not being a major concern for the pair, the two are racing to clear up the one safety area in which filgotinib may have a disadvantage: testicular toxicity.
At one point, a potential link between filgotinib and testicular toxicity raised fears that regulators would bar Gilead and Galapagos from trialing a 200 mg dose. Those fears proved to be unfounded, but Gilead and Galapagos included a dedicated male patient testicular safety study in the late-phase program to further probe the link, which is ongoing.
Data from this should be out in the third quarter, which Jefferies said in a note to clients this morning, could see a speedy charge for approval if all is well.
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On the safety side for FINCH 3, data show one venous thrombotic event (in the MTX group), five cases of adjudicated major adverse cardiovascular events (two in the filgotinib 200 mg plus MTX group, one in the filgotinib 200 mg group and two in the MTX group) and one malignancy (in the MTX group).
And most seriously, there was one death, reported in the filgotinib 200 mg plus MTX group. But analysts at Jefferies said “efficacy/safety still looked clean/comparable to competitor data (e.g. AbbVie and Lilly), supporting our view that filgotinib may have the potential for multibillion-dollar peak sales over time,” despite likely being fourth to market.
And there was also data out of the FINCH 1 test, pitting the drug against AbbVie’s major blockbuster Humira, or a placebo, on a stable background dose of methotrexate in patients with prior inadequate response to methotrexate.
This also hit its primary endpoint for both doses of 100 mg and 200 mg filgotinib in the ACR20 test, when compared to placebo at Week 12. But when comparing low disease activity rates at Week 12, filgotinib 200 mg was only non-inferior to Humira—i.e., not better or worse.
On safety, there were more deaths: five to be precise, with two patients coming out of the placebo group, two to the filgotinib 200 mg group and one to the filgotinib 100 mg group.
And five patients with a malignancy were also reported: Three receiving placebo, one receiving Humira and one receiving filgotinib 100 mg, respectively.
Jefferies said overall on safety, “Deaths look balanced, malignancies lower, and cardiovascular MACE events similar, if not lower. These trends are generally seen in each individual study.”
The data build on the FINCH 2 test, announced last September, which also hit its primary endpoint, as well as all secondaries.
The pair are also testing the drug across a range of other inflammatory disorders, including mid-to-late-stage trials in psoriatic arthritis; ankylosing spondylitis; Crohn’s disease; and ulcerative colitis.
Gilead bought its way into the JAK1 field when it paid Galapagos $725 million for rights to filgotinib. Since then, the pair has embarked on a multifront clinical campaign designed to establish filgotinib as a credible rival to JAK inhibitors from Pfizer, Eli Lilly and AbbVie.
Pfizer’s Xeljanz and Lilly’s Incyte-partnered Olumiant are on the market but have been dogged by safety issues. AbbVie’s JAK inhibitor is still in development but has a comfortable developmental lead over filgotinib.
Gilead’s shares were up more than 2% on the data premarket, while Belgium-based Galapagos saw its shares jump 15% on the news.