Rheumatoid Arthritis: Return of the DMARDs
Abbott's—soon to be AbbVie's—injectable biologic drug Humira probably won't ever unseat Pfizer's Lipitor as the best selling
drug of all time, but it may come close. Sales in 2012 will likely approach $9 billion, only $4 billion away from Lipitor's
staggering $13 billion in annual sales during its heyday.
But despite Humira's ever-widening label, new orally formulated JAK inhibitors seem poised to wrest some of those dollars
away. While a degree of safety-related uncertainly looms over Pfizer's JAK3 inhibitor tofacitinib, which had its August PDUFA
decision delayed by three months (it's now November 21), most analysts are betting that the drug will be approved this year.
Even so, "we don't think tofacitinib is going to take a bunch of share from the anti-TNFs right away," says Michael Latwis,
an analyst at Decision Resources. "Physicians will want to become more comfortable with it over time." If approved, tofacitinib
would become the first disease-modifying antirheumatic drug (DMARD) to receive approval in more than a decade; Decision Resources
puts 2018 sales at $1.2 billion, but Springer's Adis Insight sees a quicker uptake, with billion dollar blockbuster status
Despite Abbott's deft management of Humira's lifecycle, the company evidently sees oral JAK inhibitors as pillars of the future
RA treatment landscape. Last February, Abbott signed a deal with Belgium-based Galapagos (a research company founded in 1999
as a joint venture between Crucell and Tibotec, both of which are now J&J subsidiaries) for an oral JAK1 inhibitor—GLPG 0634—currently
in Phase II. The deal, worth up to $1 billion in milestone payments after an upfront payment of $150 million, and a $200 million
payment upon successful completion of Phase II (expected in 2014), puts Abbott in charge of development and commercialization
beginning with Phase III. If GLPG 0634 is eventually approved, Galapagos also gets tiered double-digit royalties on net sales,
and retains co-promotion rights in Belgium, the Netherlands, and Luxembourg. Not bad for an early-stage candidate with clinical
trials conducted exclusively in Eastern Europe.
Data from the largest of the Phase II studies is expected in November, which, if positive, means "we can legitimately consider
a potentially best-in-class among the orals," says Selvaraju. Incyte and Lilly are co-developing baricitinib, also an oral
JAK inhibitor in Phase II. Selvaraju says all efficacies being equal, the Galapagos drug "is much safer than tofacitinib,
and much safer than [baricitinib], because it's specific to a certain subtype of the Janus kinase. That is why Abbott went
after it with such alacrity." With an estimated approval date set for January 2017, GLPG 0634 almost certainly won't be the
first oral JAK inhibitor to market in RA, but then, Humira wasn't the first anti-TNF to market, either.
Bucking the oral JAK inhibitor trend in RA is Rigel Pharmaceuticals and AstraZeneca's fostamatinib, an oral Syk kinase inhibitor,
currently in Phase III. Michael Latwis, at Decision Resources, predicts that fosamatinib will launch in 2015, and bring in
$450 million in sales by 2018. Adis Insight has it doing slightly better, with sales close to half a billion in 2016, and
$651 million in 2018.