Therapy focus – Baricitinib revives Jak attack on Humira

Analysis

AbbVie’s recent contention that biosimilar competition would not hit Humira until 2022 might have raised some eyebrows – but even if this is the case its sales could still suffer in the near future as new drug classes come onto the market.

At the head of this chasing pack is Lilly and Incyte’s Jak inhibitor baricitinib, which recently beat Humira in a head-to-head trial (see tables below). This also has the advantage of being an oral agent, while other incoming rheumatoid arthritis contenders like the IL-6 and IL-23 MAbs are injected.

The first Jak inhibitor, Pfizer’s Xeljanz, has disappointed, struggling to compete with anti-TNF agents on efficacy, and the company’s attempt to expand into new diseases such as psoriasis have come up against a brick wall (Xeljanz stumbles again with US knockback, October 15, 2015).

Beam in spotlight

But baricitinib’s latest success looks like it could revive the Jak-targeting class. The results, from the RA-Beam study presented at the ACR meeting on November 10, mean that it should quickly become the oral treatment of choice over Xeljanz, according to Leerink analysts – and it might even challenge the likes of Humira, especially if Lilly prices it in line with anti-TNF biosimilars.

The analysts jacked up their 2026 forecast for baricitinib from $1.2bn to $2.8bn.

Lilly had already disclosed that baricitinib was better than Humira on the primary endpoint of ACR20 at 12 weeks – a measure representing a 20% improvement in RA disease activity.

The full results paint an even better picture, with baricitinib also coming out on top on ACR50 and 70 at week 12, as well as besting AbbVie’s drug on ACR20 and 70 at week 24.

Selected RA-Beam study results
Percentage of patients achieving response at week 12 Percentage of patients achieving response at week 24
Placebo Baricitinib Humira Placebo Baricitinib Humira
ACR20 40 70*+ 61* 37 74*+ 66*
ACR50 17 45*++ 35* 19 50* 46*
ACR70 5 19*+ 13* 8 30*+ 22*
*p≤0.001 vs placebo; +p≤0.05 vs Humira; ++p≤0.01 vs Humira.

Let’s Begin

Perhaps even more compelling were data from the RA-Begin trial, which could prime baricitinib for first-line use. The study tested it both against and in combination with methotrexate, in patients with limited or no prior treatment with methotrexate, and who were naïve to other disease-modifying antirheumatic drugs.

The primary endpoint was noninferiority to methotrexate monotherapy, measured using ACR20 at 24 weeks, and was met while also showing superiority to the older drug.

The latest results build on the already reported positive data from the RA-Build and RA-Beacon trials and put baracitinib on track for approval, expected as early as next year.

Selected RA-Begin study results
Percentage of patients achieving response at week 12 Percentage of patients achieving response at week 24
Methotrexate Baricitinib Baricitinib + methotrexate Methotrexate Baricitinib Baricitinib + methotrexate
ACR20 59 79** 77** 62 77* 78**
ACR50 33 55** 60** 43 60* 63**
ACR70 16 31** 34** 21 42** 40**
*p≤0.01 vs methotrexate; **p≤0.001 vs methotrexate.

While baricitinib is looking increasingly like an important contender in RA, it is not the only new entrant that could hurt Humira.

Others seeking approval in the next few years include the IL-6-targeting candidates sarilumab from Sanofi and sirukumab from GlaxoSmithKline and Johnson & Johnson, and another J&J agent, the anti-IL-23 MAb guselkumab. The last of these, however, is set to reach the market first for psoriasis (Upcoming events: Voyage ending for guselkumab and binimetinib, October 16, 2015). 

Astellas Pharma also has a Jak inhibitor, peficitinib, which was dropped by J&J last year. Two phase III studies are expected to read out in 2017.

Selected RA projects in phase III development
Agent Company Class 2020e sales ($m)
Baricitinib Lilly JAK-1/2 inhibitor 867
Sarilumab Sanofi/Regeneron Anti-IL-6 MAb 541
Sirukumab Glaxo/J&J Anti-IL-6 MAb 461
Guselkumab J&J Anti-IL-23 MAb 153
Peficitinib (ASP015K) Astellas Pharma JAK inhibitor 28

Meanwhile, AbbVie’s ABT-494 and Galapagos’s filgotinib could be set for a showdown. AbbVie spurned filgotinib to focus on its own Jak-targeting agent, and currently there seems to be little difference between them on efficacy, judging by phase II results (For AbbVie filgotinib becomes no-go-tinib, September 25, 2015). 

Detailed safety data with ABT-494 in the Balance-I phase II study, also presented at the ACR meeting, suggested a similar profile, although filgotinib might have the edge on certain measures including haemoglobin and natural killer cell levels, particularly when compared with higher doses of ABT-494. AbbVie is planning to take ABT-494 into phase III by the end of the year, and the dose it chooses will be watched carefully.

It will be interesting to see whether the company’s decision to ditch filgotinib pays off. Galapagos, meanwhile, is stranded unless it can strike another partnership – and probably nothing but a big pharma company will fit the bill; perhaps a revival of interest in Jak could help it find one.

To contact the writer of this story email Madeleine Armstrong in London at madeleinea@epvantage.com or follow  @medtech_ma on Twitter

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