JAK Inhibitor Setback: AbbVie’s Rinvoq Faces Second Delay for PsA and AS Applications

Compiled by | Fan Dongdong

The safety concerns previously associated with Pfizer’s Xeljanz have led to increasingly stringent scrutiny by the U.S. Food and Drug Administration (FDA) of JAK inhibitor drugs, including AbbVie’s Rinvoq, whose expansion into additional indications currently remains stalled.

According to the latest updates, the FDA will be unable to make a decision on the approval of Rinvoq for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) as originally scheduled in June. AbbVie did not specify whether the agency has provided a new decision date. This marks the second delay in the decision timeline for Rinvoq’s psoriatic arthritis indication.

According to AbbVie, in making the decision to delay Rinvoq, the FDA stated that it is still reviewing Pfizer's data. In February of this year, the agency issued a warning to patients and healthcare providers regarding safety signals associated with Xeljanz, stating at the time that it would conduct an in-depth review of the data and consider potential future actions. Currently, JAK inhibitors marketed in the United States, including Rinvoq, already carry safety warnings on their product labels regarding an increased risk of thrombosis. Evidently, the cardiovascular safety signals associated with Xeljanz have led the FDA to question whether such adverse effects represent a class-wide concern for all JAK inhibitors.

Pfizer’s JAK inhibitor Xeljanz prompted the FDA to raise safety concerns regarding the JAK inhibitor class after a post-marketing study in patients with rheumatoid arthritis revealed additional risks of serious cardiac adverse events and cancer. The study demonstrated that, compared with conventional TNF blockers, the use of JAK inhibitors significantly increased the risk of cardiac-related adverse events in patients aged 50 years or older with at least one underlying cardiovascular risk factor.

Additionally, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has also issued a safety warning, imposing prescription restrictions on Pfizer’s oral JAK inhibitor Xeljanz. Physicians are prohibited from prescribing the 10 mg twice-daily dosage to patients at high risk of pulmonary embolism. Nevertheless, Piper Sandler analyst Christopher Raymond expressed an optimistic outlook in a report on Friday, noting that given AbbVie’s drug selectively targets JAK1 and has demonstrated a favorable cardiovascular and cancer safety profile in clinical trials, it is unlikely that Rinvoq will face the same outcome as Xeljanz.

Rinvoq demonstrated incidence rates of approximately 0.4 and 0.8 events per 100 patient-years, respectively. However, Raymond also acknowledged that the recent review delays and the FDA's concerns regarding Xeljanz "have clearly created additional hurdles and skepticism surrounding the prospects for Rinvoq's label expansion." The revised regulatory timeline has indeed called into question AbbVie's previous target of achieving $8 billion in Rinvoq sales by 2025. Nevertheless, Raymond stated that hope has not been entirely lost. He noted that the positive opinion from the European Medicines Agency (EMA) reviewers regarding the approval of Rinvoq for atopic dermatitis serves as a favorable sign, indicating that the drug will ultimately secure FDA approval.

To date, the FDA has delayed multiple decisions regarding the expanded indications for this drug. In addition to psoriatic arthritis and ankylosing spondylitis, the FDA has also postponed the regulatory decision date for Rinvoq in atopic dermatitis to July of this year. Other drugs that have faced a similar fate include Xeljanz for ankylosing spondylitis, Eli Lilly's Olumiant, Pfizer's investigational abrocitinib for atopic dermatitis, as well as Incyte's Jakafi for chronic graft-versus-host disease and ruxolitinib cream for eczema.

Earlier this month, the FDA extended by three months the approval decision date for Jakafi’s regulatory application for the treatment of steroid-refractory chronic graft-versus-host disease (cGVHD), setting a new target decision date of September 22 for this indication. Notably, as the immunology blockbuster Humira is poised to lose its U.S. patent protection in 2023, Rinvoq and Skyrizi will be tasked with offsetting AbbVie's anticipated revenue shortfall.

Source: AbbVie's big Rinvoq ambitions—and the larger JAK class—face even more uncertainty with latest FDA delays