Eli Lilly has said its rheumatoid arthritis (RA) candidate baricitinib was effective in reducing symptoms in a phase IIb trial and has now been moved into late-stage testing.
The drug is a Janus kinase (JAK) inhibitor in the same class as Pfizer’s blockbuster-in-waiting Xeljanz (tofacitinib), which was approved in the US last week.
Lilly licensed it from Incyte under the terms of a collaboration signed by the two companies in 2009, which included $90m upfront and up to $665m in milestone payments plus royalties.
The latest data from the study of baricitinib in patients with moderate-to-severe RA who had an inadequate response to treatment with methotrexate (MTX) showed that Lilly’s drug was effective out to 24 weeks.
Seventy-eight per cent of patients who received the middle (4mg) dose achieved a 20 per cent improvement in joint symptoms (an ACR20 response), while 48 per cent achieved a 50 per cent improvement (ACR50) and 28 per cent improved by 70 per cent (ACR70).
Twelve-week results from the study were presented in June and indicated that baricitinib started having a positive impact in RA as early as two weeks after the start of treatment.
Encouragingly, “the percentage of patients achieving ACR50 and ACR70 increased over time and no unexpected safety findings emerged with continued dosing”, commented Mark Genovese of Stanford University School of Medicine, a member of the steering committee for the study.
Screening has begun for the phase III clinical programme in RA, which will span four studies and test baricitinib at doses of 2mg and 4mg per day. A higher dose (8mg) appeared to be little more effective than 4mg in the phase IIb trial.
The pivotal trials will include patients that have already been treated with TNF blockers such as Abbott Laboratories’ Humira (adalimumab) and Amgen/Pfizer’s Enbrel (etanercept) and disease-modifying anti-rheumatic drugs (DMARDs) such as MTX, as well as treatment-naïve patients.
Although baricitinib is some distance behind Xeljanz in development, Lilly and Incyte believe it has properties that will allow it to make an impact if it reaches the market.
It is dosed less frequently than Xeljanz – once a day rather than twice-daily – and may also have a cleaner safety profile than Pfizer’s drug as it has fewer “interactions and enzyme inhibitions”, said Incyte’s chief drug development and medical officer Rich Levy on a recent conference call.
“I think … that there will be a substantial market for baricitinib, and the potential that it could actually be the number one JAK inhibitor for rheumatoid arthritis … despite a launch a few years later,” he added.
Lilly is also conducting phase II trials of baricitinib in psoriasis and in diabetic nephropathy.