The FDA Arthritis Advisory Committee voted 10 to 5 to recommend approval of a once-daily 2-mg dose of baricitinib for the treatment of adults with moderate to severe rheumatoid arthritis who have had an inadequate response to methotrexate.
Although the committee was near-unanimous on the positive efficacy of baricitinib (Olumiant, Incyte & Eli Lilly), its safety was much more controversial, with just a 9-member majority agreeing that the available data supported the safety of the 2-mg dose.
By a 10 to 5 vote, the committee voted against approval support for a 4-mg once-daily dose of baricitinib citing safety concerns, particularly the risk for venous and arterial thrombosis.
“I voted yes because I felt the company did a better job with this dosage [4 mg], understanding the signal concerning adverse effects, and clearly showed that the drug is efficacious and resistant to rheumatoid arthritis,” Irwin J. Russell, MD, PhD, a member of the panel from the Arthritis and Osteoporosis Center of South Texas in San Antonio, said of his favorable vote on the safety profile of baricitinib 4 mg. “Rheumatoid arthritis is a devastating disease — organs and joints are being destroyed — and it is war, and we need to make the patients aware that it is war and fight it like it is.”
The FDA Arthritis Advisory Committee voted 10-to-5 against approving a higher dose of baricitinib for patients with rheumatoid arthritis, but recommended its lower dose counterpart for approval.
According to the FDA, both barcitinib 2-mg and 4-mg are effective in reducing signs and symptoms, and in improving physical function, among patients with RA, compared to a placebo. Both exhibited higher American College of Rheumatology 20%, 50% and 70% improvement figures than placebo at weeks 12 and 24. In addition, both doses demonstrated improvement in patients’ Health Assessment Questionnaire-Disability Index relative to placebo.
Regarding radiographic response, the data on the 4-mg dose demonstrated a “robust” efficacy, the FDA reported. However, the 2-mg dose produced uncertainty, as its radiographic response was examined in only one study as an exploratory endpoint.
The FDA’s safety findings for baricitinib warned of risks for serious infection, including herpes zoster and tuberculosis, as well as malignancy, venous and arterial thrombosis and laboratory abnormalities.
In addition, the FDA also reported to the committee the drug’s safety data included limited controlled comparisons, as well as limited exposure information for both doses.
“The question was about whether or not there was adequate safety data for the 2-mg dose, and the answer is, scientifically, no,” Jose Scher, MD, the committee’s acting chairperson, who voted against recommending both doses of the drug, said. “Beyond the lack of rigor, in terms of statistically significantly adequate numbers, there just isn’t enough information. All we have instead is opinion, and I can’t vote based on opinion.”
Eli Lilly and Incyte Corporation had initially submitted their application for baricitinib to the committee in January 2016, but was required to resubmit after the FDA issued a complete response letter due to the unfavorable benefit-risk regarding the potential risk for thrombosis.
In the most recent submission for the drug, issued in December 2017, the companies included new safety and efficacy data, and recommended a warning label for venous thromboembolism. Eli Lilly added that the risk for venous thromboembolism should be monitored in post-approval studies.
According to a spokesperson for Eli Lilly, the company expects the FDA to rule on baricitinib’s final approval sometime before the end of the second quarter of 2018.
In a statement released following the meeting, Eli Lilly and Incyte noted that Baricitinib 2-mg and 4-mg are approved in more than 40 countries, including Japan and the member states of the European Union.
“We are confident that baricitinib, if approved, can help people in the United States manage the challenges of living with RA,” Christi Shaw, president of Lilly Bio-Medicines, said in the release. “While we are disappointed with the advisory committee’s assessment of the data for the 4-mg dose, we are confident in the positive benefit-risk profile of both the 2-mg and the 4-mg doses. We look forward to continuing our work with the FDA on our New Drug Application and are hopeful that baricitinib will receive approval in the coming months.” – by Jason Laday