Key data for the last few oral antirheumatics
Remember when in the early part of the decade it was widely held that cheap, oral antirheumatic drugs would shortly replace expensive, injectable anti-TNF agents for rheumatoid arthritis? Well, that seems rather rash now.
Pfizer’s Jak inhibitor Xeljanz, the lead agent in this class, did make it to the market in 2012 but has failed to live up to expectations, while its close competitors, including AstraZeneca and Rigel's syk inhibitor fostamatinib, have been dropped from development. With the once-rich pipeline quietly whittled down to perhaps six oral agents in late development today, it is now the turn of Lilly's baricitinib to show whether an oral agent can still reshape the RA space.
Results are due from trials of several other agents too, but baricitinib appears to be the most important. Consensus sales forecasts for it stand at $650m in 2020, according to EvaluatePharma. The most important trials of baricitinib, a Jak-1/2 inhibitor, are two phase III studies known as RA-Begin and RA-Beam.
RA-Beam enrolled 1,280 patients with an inadequate response to methotrexate and tested 4mg of baricitinib versus AbbVie’s Humira as well as placebo. RA-Begin tests two doses of baricitinib versus placebo in 550 patients with limited or no treatment with methotrexate, and who are naïve to other conventional or biological disease-modifying antirheumatic drugs (DMARDs).
Lilly has already reported positive results for two other phase III trials, RA-Build and RA-Beacon, and replication of these data should ensure baricitinib's place in the market.
That place may not go unchallenged. An important competitor, AbbVie, will shortly have to make a decision on whether to opt into a pre-negotiated licensing agreement with Galapagos for the Belgian company’s selective Jak-1 inhibitor, filgotinib. AbbVie paid $150m in 2012 to secure the option, with a further $200m payable on exercise and further milestones of up to $1bn and tiered double-digit royalties.
That decision is now looming and will be based on 24-week data from two phase II studies expected in the next few weeks (Galapagos moves towards RA deal but a dark horse remains on the horizon, April 15, 2015).
Although the full Phase III data on baricitinib would be an important consideration for AbbVie, one other factor within its control is the outcome of a phase II study of an internally developed Jak-1 inhibitor, ABT-494. This trial has recently been completed, so presumably results are already available.
Analysts covering Galapagos have assumed that AbbVie will exercise its option, though competition in the Jak inhibitor area is fierce. This was presumably behind J&J’s decision last December to discontinue a joint project with Astellas for the only other Jak inhibitor in development, ASP015K.
J&J had held ex-Japan rights. Astellas is continuing Japanese development, with two phase III studies under way and due to render results in March 2017.
There are only two other oral DMARDs in mid to late development: Celgene’s BTK inhibitor, CC-292, and Pfizer’s selective glucocorticoid receptor modulator, PF-04171327.
With much at stake commercially, decisions taken in the next few months could determine whether oral agents – other than methotrexate – do become a new standard in the treatment of RA.
|Study||Project||Design||ACR20 responses||ACR50 responses||ACR70 responses|
|RA-Build||Baricitinib||684 pts, placebo vs 2mg & 4mg||61% & 65% (both p<0.001) vs 42%||42% & 44% (both p<0.001) vs 22%||25% & 24% (both p<0.001) vs 8%|
|RA-Beacon||Baricitinib||527 pts, placebo vs 2mg & 4mg||45% & 46% (both p<0.001) vs 27%||23% (p<0.05) & 29% (p<0.001) vs 13%||13% & 17% (both p<0.001) vs 3%|
|Darwin-2||Filgotinib||283 pts, placebo vs 50mg, 100mg & 200mg||67%, 66% & 73% (all p<0.001) vs 31%||36%, 34% (both p<0.01), 44% (p<0.001) vs 11%||8%, 19% (p<0.05), 13% (others NS) vs 4%|