- Gilead Sciences and partner Galapagos said Thursday their investigational anti-inflammation drug succeeded in a Phase 2 trial of patients with moderate to severe ankylosing spondylitis, a kind of arthritis that causes pain and swelling in the joints.
- Patients taking the drug, filgotinib, experienced significantly greater improvements in disease activity after 12 weeks than those who received placebo. Additionally, 76% of filgotinib-treated patients versus 40% of placebo-treated patients achieved an ASAS20 response, meaning they had at least a 20% improvement in several measures of disease severity.
- The trial's two arms showed similar proportions of adverse events, according to Gilead and Galapagos. However, there was one patient on filgotinib who experienced a serious, treatment-emergent case of pneumonia. Also, one patient with an inherited risk of blood clots had a non-serious deep vein thrombosis during the period following filgotinib treatment.
Filgotinib is part of a growing class of anti-inflammatory agents which inhibit Janus kinases, enzymes that play a role in immune responses.
The first JAK-blocking therapy to gain Food and Drug Administration approval in humans was Pfizer's Xeljanz (tofacitinib) in 2012 for the treatment of rheumatoid arthritis (RA). Two others have since come to market, though only one — Eli Lilly and Incyte's Olumiant (baricitinb) — also carries an RA indication.
Gilead and Galapagos are looking to add filgotinib to that short list. The drug is already in three late-stage RA trials, with the earliest set to complete in December. Though Wall Street expects filgotinib to gain approval and eventually become a blockbuster, there are obstacles to clear before that can happen.
For one, analysts predict filgotinib will be the fourth JAK inhibitor for RA to hit the market, behind Xeljanz, Olumiant and AbbVie's investigational drug upadacitinib.
Some labeling setbacks have made Lilly's drug less of a competitive threat, but the same can't be said for Xeljanz and upadacitinib. Revenue from the Pfizer product grew more than 150% from 2015 to 2017, reaching $1.35 billion last year. And upadacitinib has proven both clean and effective in the clinic, supporting AbbVie's ambitious goal of $6.5 billion in annual sales for the drug by 2025.
Regulators could also take issue with the deep vein thrombosis event seen in the Phase 2 TORTUGA trial. Though the event doesn't appear treatment-related, a chief concern with Olumiant was that it could increase the potential for blood clotting — and that concern may bleed over to filgotinib.
"Given the safety concerns with baricitinib and also with tofacitinib, I wonder if the ones in development will be more carefully scrutinized before they are approved, perhaps according to their JAK-specificity," Aruni Jayatilleke, an associate professor in the division of rheumatology at Drexel University College of Medicine, wrote in an email to BioPharma Dive earlier this year.
To that point, Jefferies analyst Michael Yee said the focus will be on safety when upcoming data from Phase 3 FINCH 2 trial of filgotinib in adults with RA who haven't adequately responded to biologic disease modifying anti-rheumatic drug become available.
There's also the longer-term question of whether filgotinib can out-class upadacitinib. In a Sept. 6 investor note, Yee wrote that the drug could theoretically have a best-in-class profile, but acknowledged that some may be wondering about whether "filgotinib differences matter enough to the managed care formularies if rebating is ultimately the deciding factor and it's 1-2 years behind [upadacitinib]?"
Still, Gilead and Galapagos have been high on filgotinib's prospects and are assessing it across a handful of other diseases, including ulcerative colitis, Crohn's disease and psoriatic arthritis.