AbbVie has moved a step closer to getting its JAK inhibitor upadacitinib onto the market for rheumatoid arthritis (RA) after a positive phase III trial.
The selective JAK1 inhibitor – which is vying to become the third drug in the class after Pfizer’s Xeljanz (tofacitinib) and Eli Lilly’s Olumiant (baricitinib) – met the objective of improving symptoms and dampening down disease activity in RA patients compared to prior stable methotrexate therapy in the SELECT-MONOTHERAPY study.
There was a fatality from a stroke in the trial in a patient, plus one case of a pulmonary embolism, although AbbVie said these occurred in at-risk patients. These come after a couple of deaths in earlier trials of the drug, and come against a backdrop of FDA concerns about the safety of the class with regard to thrombosis.
Thrombosis fears caused it to reject Olumiant, forcing Lilly to re-file the drug earlier this year, although it has been approved in Europe. However, analysts at Jefferies have suggested the clots are more likely to arise from the disease than the drug treatment.
AbbVie’s chief scientific officer Michael Severino said the findings were “encouraging, as they are the first evidence to support the potential of upadacitinib as a therapy without the need for background methotrexate”. Its earlier trials in RA have compared the drug to placebo on top of methotrexate therapy.
After 14 weeks’ treatment, 68% of patients on a lower dose of AbbVie’s drug and 71% on a higher dose had a 20% improvement in symptoms (known as an ACR20 response) after switching from methotrexate therapy, compared to 41% who remained on that regimen. Meanwhile, low disease activity (LDA) was achieved in 45% of the low-dose upadacitinib group, 53% of the high-dose group and just 19% of those staying with the comparator drug.
Similar patterns were observed on ACR50 and ACR70 measures, with both doses of upadacitinib outperforming methotrexate, and clinical remission was achieved in 28%, 41% and 8% of patients, respectively.
Upadacitinib (also known as ABT-494) has been tipped by some analysts as a future leader of the category with sales of up to $3.5bn. Xeljanz is still growing strongly as an oral alternative to biologic medicines for RA, with sales rising 44% to $935m in the first nine months of 2017. Olumiant has been pegged back by the FDA rejection and made just over $22m in the same period after getting the green light in Europe in February.
AbbVie’s closest rival for third place is former partner Galapagos, which is brining filgotinib forward in phase III trials with new collaborator Gilead.