The regulatory agency just placed new safety warnings on that drug class, which will impact AbbVie’s Rinvoq (upadacitinib), a drug the company has seen as a successor to its revenue-driving Humira.
The U.S. Food and Drug Administration (FDA) is expressing more concern about potential safety issues with JAK inhibitors. The regulatory agency just placed new safety warnings on that drug class, which will impact AbbVie’s Rinvoq (upadacitinib), a drug the company has seen as a successor to its revenue-driving Humira.
The move followed an FDA review of the post-marketing ORAL Surveillance study that assessed Pfizer’s Xeljanz (tofacitinib), a JAK inhibitor for the treatment of rheumatoid arthritis. The post-marketing study results showed a higher rate of major adverse cardiac events (MACE), malignancy, mortality, and thrombosis in patients who received Xeljanz.
Blood clots and lymphoma are already listed as boxed warnings for this class of drugs.
There are currently three-approved JAK inhibitors for rheumatoid arthritis – Rinvoq, Xeljanz and Eli Lilly’s Olumiant.
Rinvoq was first approved as a treatment for rheumatoid arthritis in 2019. It has gained regulatory approval for the treatment of active psoriatic arthritis and active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy.
Following the FDA review, the agency demanded label changes to all drugs in the class, which includes AbbVie’s Rinvoq. The label now has additional information about the risks of malignancy and thrombosis and the addition of mortality and MACE. The boxed warning comes as the company seeks regulatory approval for Rinvoq in additional indications, including atopic dermatitis, psoriatic arthritis, ankylosing spondylitis and ulcerative colitis.
The update to Rinvoq’s label, as well as other JAK inhibitors, follows an FDA proclamation in September that required pharmaceutical companies to warn patients about the risks of this drug class. As BioSpace previously reported, the FDA said that all approved medications that involve JAK inhibitors aimed at the treatment of chronic inflammatory diseases require warnings about an increased risk in cardiovascular events, as well as cancer, blood clots or death. At the time the FDA warning was issued, the regulatory agency said that Lilly’s Olumiant and Rinvoq had not been studied in trials similar to the large safety clinical trial with Xeljanz. That means that the risks of those drugs have not been adequately evaluated. However, the agency said that since those drugs share similar mechanisms of action, the FDA considered them to have similar risks that were seen in the post-marketing study of Xeljanz.
The FDA review was sparked by concerning safety data from Pfizer regarding its JAK inhibitor, Xeljanz. Earlier this year, Pfizer initially noted concerns in patients who received a twice-per-day 10 mg dose of the medication. Data showed those patients were at greater risk of a pulmonary embolism. After that announcement, Pfizer said it was shifting those patients from 10 mg to 5 mg twice per day.
In addition to rheumatoid arthritis, Xeljanz has also been approved by the FDA for psoriatic arthritis.
JAK inhibitors, or Janus kinase inhibitors, are designed to block the activity of one or more of the JAK enzymes in the body, as well as the signaling pathway.
Despite the safety risks seen in JAK inhibitors, Michael Severino, AbbVie’s vice chairman and company president, said Rinvoq is an important treatment for RA patients who have not responded well to TNF blockers, which includes Humira and other drugs such as Enbrel and Remicade.
“We remain committed to continue generating evidence that support its (Rinvoq’s) benefit-risk profile across many inflammatory conditions,” Severino said in a brief statement.
In June, AbbVie announced data that showed Rinvoq demonstrated significant efficacy as a maintenance drug in ulcerative colitis patients. At the time of the announcement, the company said more patients who received Rinvoq achieved clinical remission of their symptoms compared to placebo.
Following the FDA crackdown on JAK inhibitors in June, AbbVie announced a delay in potential approval for Rinvoq in active psoriatic arthritis and adults with active ankylosing spondylitis. AbbVie said the FDA cited its ongoing review of the ORAL Surveillance post-marketing study as a reason for the delay of the sNDA. Rinvoq is estimated to generate about $2 billion in revenue annually for AbbVie by 2025.
