Gilead bolsters its case for blockbuster hopeful filgotinib as FDA ponders its decision
Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.
Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.
Last October, the companies showed that the drug’s 52-week data from the two main trials FINCH 1 and FINCH 3 were consistent with their 24-week results. On Thursday, further analyses of the data suggested that patients on the filgotinib arm had a numerical advantage in remission rates.
At the 24-week cutoff, 48% of patients enrolled in the higher 200 dose of filgotinib arm were in remission in the FINCH 1 trial that compared the drug to adalimumab (AbbVie’s Humira). By the end of 52 weeks, that remission rate rose to 52%. The percentage in the Humira arm rose too, but the numbers favored filgotinib across multiple measures of efficacy. Data from the FINCH 3 trial echoed that trend.
Filgotinib’s biggest rival is AbbVie’s Rinvoq — the replacement for its cash cow and world’s best selling drug Humira. Rinvoq is slated to be a blockbuster, but carries the dreaded black box warning for thrombosis, even though the event was rare in AbbVie’s development program.
The move by the FDA is more precautionary given that the JAK class of drugs has long been plagued by safety concerns. Pfizer’s JAK1/JAK3 inhibitor Xeljanz’s use has been blighted by regulatory restrictions after the higher dose of the blockbuster drug was found to be associated with the risk of blood clots and death. Eli Lilly’s JAK1/JAK2 Olumiant, meanwhile, was initially rejected by the US agency due to safety concerns — only to eventually secure approval for the lower dose. Lilly’s partner, Incyte, elected to walk away from co-funding the drug’s development as fears about the benefit-risk profile of the class of drugs accumulated.
Galapagos $GLPG, which once partnered with AbbVie on filgotinib, has presented itself as a safer alternative to its rivals using a pooled analysis of safety data compiled from seven rheumatoid arthritis trials. The analysis showed that the rate of venous thromboembolism, a key safety concern, was lower in patients given filgotinib versus those on placebo.
“While filg’s profile has been quite clean so far, given the history of Jak inhibitor approvals/rejections, we believe the biggest risk to the program remains if any safety imbalances (even if seemingly minor) emerge and derail approvability of the most active high dose (200mg) of the drug, or of the drug altogether,” noted RBC Capital Markets analyst Brian Abrahams in a note.
“In analyzing the detailed data, we do not see any major new concerns and continue to see a good likelihood of approval, with a low serious infection rate providing a potential safety advantage vs. competitors. However, we do see a slight imbalance in overall deaths for higher vs. lower dose filgotinib that could be scrutinized by the agency and may be a small risk to keep an eye on.”
Gilead paid $750 million upfront to partner with Galapagos years ago, expanding the collaboration to an up-to $5.1 billion deal last year. Filgotinib, which is at the heart of the deal, is also being tested for other autoimmune conditions such as Crohn’s disease, ulcerative colitis and psoriatic arthritis. Last October it was revealed the drug failed mid-stage studies in lupus and Sjögren’s disease.
Janus kinase (JAK) inhibitors are named after the two-faced Roman god Janus and the family consists of four enzymes: JAK1, JAK2, JAK3 and TYK2, which are associated with cytokine receptors on the surface of cells and form part of a pathway involved in inflammatory and immune responses.