Generic name: upadacitinib
Disease: rheumatoid arthritis
2024 sales estimate: $2.18 billion
Even as AbbVie’s industry-leading Humira faces its eventual sales decline, the company can be thankful that it has two out of the three top launches of 2019, based on 2024 sales.
Trailing Ultomiris in 2019 launch rankings is upadacitinib, AbbVie’s candidate for moderate to severe rheumatoid arthritis. In a March report, analysts with Cortellis said the drug is expected to score a U.S. nod in August and European approval in October. It’ll generate $2.18 billion by 2024, they said.
The launch won't be without its challenges. Upadacitinib is a once-daily oral JAK1-selective inhibitor, and some red flags have popped up for the JAK class. In a postmarketing safety study of Pfizer's Xeljanz, monitors noted an increased incidence of pulmonary embolism for patients on the higher dose. Pfizer switched participants over to the lower dose, and news of the change triggered questions about other JAK drugs.
In fact, Xeljanz is not the only JAK inhibitor that the FDA has flagged over safety concerns. The FDA only approved the lower dose of Eli Lilly's Olumiant, spurning the higher one because of safety worries.
And upadacitinib put up a couple of CV events in its own clinical testing. A hemorrhagic stroke death and a pulmonary embolism—both in patients the pharma says had “pre-existing cardiovascular risk factors”—marred phase 3 results for the low-dose group.
The potential classwide safety issues could throw a wrench in AbbVie's plans. JAK inhibitor side effects—which can include infections and elevated cholesterol—have until now been considered “more acceptable” in rheumatoid arthritis than those of its rival TNF-alpha drugs, Bernstein analyst Ronny Gal has written.
Whether the new worries hit sales remains to be seen, though, and Lilly, for one, recently presented longer-term Olumiant data showing no increase in DVT or pulmonary embolism for the higher dose FDA had questioned. And before the Xeljanz news surfaced, Gal predicted JAKs could snap up 24% of the RA market, threatening second-line choices such as Amgen’s Enbrel.
AbbVie is hoping to expand upadacitinib beyond RA, too. The company is investigating the drug as a treatment for Crohn’s disease, psoriatic arthritis, atopic dermatitis, ulcerative colitis and axial spondyloarthritis.
Amid its upadacitinib ramp-up, AbbVie will face growth pressure on its stalwart RA drug Humira, which pulled in nearly $20 billion last year. Biosims are already on the market in Europe, and in the first quarter of 2019, AbbVie said the drug’s international sales slipped 23% to $1.2 billion. U.S. sales, meanwhile, climbed 7% to $3.2 billion. U.S. biosimilars are set to reach the market in 2023.