- Gilead and Galapagos' experimental rheumatoid arthritis drug proved effective at reducing joint tenderness and swelling in two large Phase 3 studies, delivering a needed trial win for the Foster City, California-based biotech and its Belgian partner.
- Importantly, results released by the companies Thursday showed little sign of the safety concerns that have dogged other therapies similar to Gilead and Galapagos' drug, called filgotinib.
- Best known for its HIV and hepatitis C medicines, Gilead aims to break into the crowded market for arthritis therapies with filgotinib, an oral drug that inhibits an enzyme known as JAK1. Success could help it find new growth, although competition from other similar drugs — particularly one developed by AbbVie — may prove challenging.
Filgotinib will likely arrive to market fourth in its drug class, after approved JAK inhibitors from Pfizer and Eli Lilly as well as one from AbbVie that's currently under review by the Food and Drug Administration.
The trial successes are particularly important for Gilead. Amid sliding sales from its hepatitis C business, Gilead has been on the hunt for new markets, turning to cancer, non-alcoholic steatohepatitis (NASH) and arthritis.
The first Phase 3 study in Gilead's efforts to develop a drug for NASH missed its goal earlier this quarter, putting Wall Street's focus more heavily on filgotinib.
FINCH 1 and FINCH 3 both tested the drug in patients with moderate-to-severe rheumatoid arthritis, a chronic, inflammatory condition that affects between 1.3 million and 1.8 million Americans.
In FINCH 1, Gilead and Galapagos compared filgotinib against AbbVie's top-selling arthritis drug Humira (adalimumab) and methotrexate, a mainstay treatment discovered in the 1940s. Patients enrolled in the study were already on a stable dose of methotrexate, but hadn't responded adequately.
Both doses of filgotinib tested led to a greater than 20% improvement in tender or swollen joint counts — a measure referred to as ACR20 — in a significantly larger proportion of patients than placebo.
On a separate measure of low disease activity, the high dose of filgotinib also proved non-inferior to Humira.
FINCH 3, by contrast, studied filgotinib as monotherapy and in combination with methotrexate among patients who had never received methotrexate.
Treatment with filgotinib plus methotrexate resulted in significantly higher proportions of patients meeting ACR20 than methotrexate alone. Filgotinib monotherapy, however, did not hit statistical significance versus methotrexate.
Both studies also looked at response rates by ACR50 and ACR70, which respectively measure 50% and 70% improvements in tender or swollen joint counts.
The efficacy of filgotinib was not very much in doubt among Wall Street analysts after positive data from a smaller but also late-stage study of the drug were presented last September.
But FINCH 1 and FINCH 3 were widely seen as key tests of filgotinib's safety.
Pfizer's Xeljanz (tofacitinib) and Lilly's Olumiant (baricitnib) — both JAK inhibitors — have black box warnings for serious infections and malignancies. Olumiant carries a further caution of thrombosis, or blood clots, a risk that led the FDA to approve only the lowest dose of the drug submitted by Lilly.
The newest data on filgotinib showed rates in all three areas to be low and balanced across trial arms. In all three FINCH studies as well as a Phase 2 study called DARWIN 3, serious infections occurred in 1.4% of patients given filgotinib, compared to 2.5% on Humira and 1.0% on placebo or conventional disease-modifying therapies like methotrexate.
Only one case of deep vein thrombosis or pulmonary embolism among filogotinib-treated patients was recorded by investigators, according to the companies.
"The overall safety data from FINCH 1, 2, and 3 and DARWIN 3 trial suggests a safety profile close to placebo and in-line or better than other leading JAK inhibitors (when compared across different trials)," wrote Vamil Divan of Credit Suisse in a March 28 note to clients.
Yet Gilead and Galapagos still have one more hurdle to clear: a safety trial studying male reproductive toxicity with filgotinib. That study, called MANTA, is now recruiting.
Whether the FDA will require those results before accepting an application for filgotinib's approval is unclear, although Jefferies analyst Michael Yee noted a filing based on interim data could be possible.
Increasingly, the question facing the partner biotechs will be how well filgotinib could compete if approved.
AbbVie's upadacitnib, in particular, would be a major challenger. The FDA is expected to decide on approval of the drug, which also blocks JAK1, by the third quarter. Prior results from AbbVie have shown strong efficacy, including superiority of upadacitinib over Humira on some measures in patients who had an inadequate response to methotrexate.
And as a class, JAK inhibitors remain challengers to the incumbent TNF inhibitors like Humira. Biosimilar versions of those older drugs could prove a further wrinkle in a market that's one of the most competitive in pharma.