The rheumatoid
arthritis market
Launch of upadacitinib is anticipated in
2019, assuming approval is granted, but
the drug would be a late entrant into a
crowded market dominated by biological
agents – many of which are recommended
for use ahead of newer agents.10
The biologicals include ones that inhibit
the pro-inflammatory mediator tumor
necrosis factor (TNF), such as Humira,
Enbrel (etanercept; Amgen/Pfizer/
Takeda), Simponi (golimumab) and
Remicade (infliximab; both Johnson &
Johnson/Merck & Co/Mitsubishi Tanabe),
and Cimzia (certolizumab pegol; UCB/
Astellas). The American College of
Rheumatology guidelines on rheumatoid
arthritis treatment recommend these
drugs as second-line therapy options after
DMARDs.10 Biosimilar versions of Humira
(2017 sales of $18.77 billion) entered the EU
market in 2018 and are set to launch in the
U.S. in 2023 – creating additional pressures
in this already complex market.11,12,13
Also recommended ahead of newer
agents are the non-TNF biologicals
such as Actemra (tocilizumab; Roche/
Chugai), Orencia (abatacept; Bristol-Myers
Squibb/Ono) and Rituxan (rituximab;
Roche/Biogen), which are positioned
as alternatives to the TNF biologicals or
after TNF inhibitor therapy failure.10
Upadacitinib will also face direct
competition from other JAK inhibitors.
First-in-class Xeljanz (tofacitinib; Pfizer)
is a broad-spectrum JAK family inhibitor
that has shown comparable efficacy
to Humira. The American College of
Rheumatology recommends it in the event
of biological therapy failure.14,15 Xeljanz sales
in 2017 were $1.35 billion, with forecast
sales rising to $3.31 billion in 2023.
Eli Lilly and Incyte’s Olumiant (baricitinib),
which is selective for JAK1/JAK2 and
has shown superior efficacy to Humira,
entered the EU and Japanese markets
in 2017 and the U.S. in 2018.16 Sales of
Olumiant were $46 million in 2017, with
sales of $977 million forecast for 2023 –
approximately half those of upadacitinib.
Olumiant faces a number of challenges:
for example, it has a black-box warning on
its label more extensive than the Xeljanz
one. Additionally, although Olumiant is
available in the EU and elsewhere as 2-mg
and 4-mg doses (the 4-mg dose is the most
commonly used, outside the U.S.), the FDA
has only approved the 2-mg dose. This
decision was based on safety concerns
with the 4-mg dose.17,18,19,20,21 However, it was
the 4-mg dose that showed superiority
to Humira in the RA-BEAM trial, and thus
the FDA’s refusal to approve that dose is
a significant blow to Olumiant, but also a
potential opportunity for upadacitinib.22