AbbVie keen on JAK inhibitor despite safety concerns
- AbbVie Inc. announced positive results Monday for what it believes could be a best-in-class Janus kinase (JAK) inhibitor, but patient deaths in the study raise concerns.
- The company reported topline results from the Phase 3 SELECT-BEYOND clinical trial, which tests upadacitinib (ABT-494) in patients with moderate-to-severe rheumatoid arthritis (RA) that are not adequately treated by biologics.
- The results showed both the 15 mg and 30 mg doses hit the primary endpoint of reducing RA symptoms by 20% over 12 weeks in 65% and 56% of patients, respectively, compared to only 28% of those on placebo.
Study results showed low disease activity was achieved by 43% and 42% of patients in the 15 mg and 30 mg groups, respectively, compared to 14% on placebo. Clinical remission was achieved by 29% and 24%, compared with 10% of patients receiving placebo.
While the safety profile of the drug was largely consistent with previous successful trials, there were two patient deaths in the study. One patient taking the 15 mg dose died of unknown causes and a patient taking the 30 mg dose died after developing fever and diarrhea and then experiencing heart failure, as well as a pulmonary embolism.
Yet, the company said investigators didn’t think the deaths were likely linked to the study drug.
"Keep in mind, the RA patient population tends to be older and sicker to begin with," wrote Evercore ISI analyst Josh Schimmer in a note to clients on Sept. 11. "They are at increased risk of lymphoma, thrombosis events, infections and more. So signals of these events must be taken with this consideration in mind, especially when comparing across settings."
While the patient deaths in the study are unlikely to derail the drug completely, it could add delays. Currently, there is only one other JAK inhibitor approved for the treatment of RA — Pfizer Inc.’s Xeljanz (tofacitinib).
Eli Lilly & Co. also has a JAK inhibitor in development, but the Indianapolis pharma hit a roadblock when the Food and Drug Administration declined to approve baricitinib. Lilly recently gave investors some new hope when it revised its timeline to resubmit, saying it will do so at the beginning of next year.
The regulator rejected the Lilly drug because of concerns about deep vein thrombosis and pulmonary embolism.
These aren’t new concerns for the class — Xeljanz was only approved at the 5 mg dose because efficacy leveled off with higher doses while risks of adverse events continued to rise.
Yet, even if AbbVie can get the drug to market, it is unlikely to completely make up for any revenue declines AbbVie might experience due to inbound biosimilar competition to its top-earner Humira (adalimumab).
Humira currently makes up more than 60% of the revenues and is one of the top-selling drugs in the world. If upadactinib secures an approval, estimates out 2020 revenue at only $375 million, rising to $1.075 billion by 2022.
- AbbVie Press release
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