Pfizer’s troubled JAK inhibitor Xeljanz has had its share of hiccups after pulmonary embolism fears derailed the drug’s higher dose in rheumatoid arthritis. Now, Pfizer is hoping for better results using Xeljanz to treat RA patients who wean off immunosuppressants.
Patients treated with a solo Xeljanz dose after 24 weeks of combo therapy with Xeljanz and anti-rheumatic methotrexate showed roughly the same disease activity at 48 weeks as patients who stayed on the immunosuppressant, Pfizer said. Those findings are part of a late-breaking data set from a double-blind phase 3/4 trial set to be presented Saturday at the European Congress of Rheumatology (EULAR) meeting in Madrid.
The drugmaker touted the data as the first of its kind to show noninferiority for a solo JAK inhibitor in RA after withdrawal from methotrexate, a powerful oral immunosuppressant often used in cancer treatment.
“From a clinical perspective, these results give physicians data to help inform the decision to take appropriate patients off methotrexate,” Stanley Cohen, of Dallas’ Metroplex Clinical Research Center, said.
The Xeljanz trial, dubbed Oral Shift, showed serious side effects in 3.8% of the 264 patients treated with 11 milligrams of the solo drug and placebo and 1.9% of patients treated with the combo therapy. Pfizer reported two deaths among patients treated with the combo therapy.
The newest data could help Pfizer make the case for increased Xeljanz use after trial setbacks and FDA scrutiny helped suppress sales of the drug.
In February, Pfizer switched RA trial patients off 10-milligram doses of Xeljanz to a lower dose after uncovering an increased risk of pulmonary embolism in a postmarketing safety study. The study, which was designed to assess cardiovascular events in patients 50 years or older with at least one risk factor, was mandated by the FDA after Xeljanz’s approval in 2012. Xeljanz, which is only approved to treat RA with its 5-milligram dose, already sports a black box warning on its label for infections and malignancy.
All of that uncertainty has spelled trouble for Xeljanz’s sales, which undershot analyst expectations in the first quarter and put pressure on Pfizer as it attempts to pick up the slack from coming generic competition to blockbuster Lyrica. Xeljanz generated $423 million in the first quarter—short of analysts' forecasts of $490 million—though Pfizer reassured investors the drug had plenty of room for growth, with launches in psoriatic arthritis and ulcerative colitis underway. Pfizer said those two indications made up a little more than one-third of the drug’s 34% growth on the quarter.
Xeljanz is not the only JAK inhibitor that the FDA has flagged over safety concerns. Eli Lilly, which has been spurned as well in its hopes for higher-dose approval for contender Olumiant, is also at EULAR to make its safety case with new trial data.
Lilly said the drug’s 4-milligram dose showed roughly the same safety profile as placebo in RA patients treated over seven years. The agency previously cited thrombosis, infection and malignancy risks in its decision to not approve the higher dose.
Meanwhile, another JAK inhibitor candidate, AbbVie’s upadacitinib, came under scrutiny of its own in late December 2017 after an RA trial death and pulmonary embolism marred the drug’s phase 3 trial.
Editor's Note: This article has been updated to correct an error. Xeljanz has a black box warning label for infections and malignancy.