FDA Approves Baricitinib for Certain Adult Patients Hospitalized With COVID-19

The FDA has approved baricitinib (Olumiant; Eli Lilly and Company and Incyte) for the treatment of adult patients hospitalized with COVID-19 who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) with a recommended dose of 4 mg once daily for 14 days or until hospital discharge, whichever happens first. The approval follows an emergency use authorization (EUA) granted in November 2020 for baricitinib in combination with remdesivir in hospitalized adults and pediatric patients.

"More than 2 years into the pandemic, COVID-19 is still hospitalizing many people and burdening our health care system. I'm grateful to have Olumiant as a treatment option for those who require various degrees of respiratory support, from supplemental oxygen to mechanical ventilation or ECMO," Andre Kalil, MD, MPH, professor of Medicine at the University of Nebraska Medical Center and principal investigator of the Adaptive COVID-19 Treatment Trial 2 (ACTT-2), said in a press release. "I'm encouraged by the FDA's full approval of Olumiant for the treatment of these patients based on results from the rigorous, placebo-controlled, double-blind, randomized trials. While there are therapies currently available, there is still an urgent need for more options to help improve outcomes for patients hospitalized due to COVID-19."

The FDA's approval of baricitinib was supported by a pair of randomized, double-blind, placebo-controlled phase 3 studies (ACTT-2 and COV-BARRIER, including the COV-BARRIER OS 7 addendum study). The EUA will remain in place for hospitalized pediatric patients aged 2 to less than 18 years who require various degrees of oxygen support.

The ACTT-2 trial compared certain hospitalized adults with confirmed SARS-CoV-2 infection administered baricitinib and remdesivir (combination group; n=515) versus treatment with placebo and remdesivir (placebo group; n=518). Individuals administered the combination received baricitinib 4-mg once daily (orally) for 14 days or until hospital discharge, and remdesivir 200-mg on day 1 and 100-mg once-daily via intravenous infusion on subsequent days for a duration of 10 days or until hospital discharge.

Baricitinib plus remdesivir achieved the ACTT-2 primary endpoint of median time to recovery: a 1-day, or 12.5% overall, improvement compared to remdesivir monotherapy (8 vs 7; incidence rate ratio [IRR], 1.16; 95% CI, 1.01-1.32; P = .04). Recovery was defined hospital discharge or removal from supplemental oxygen during hospital care at day 29.

Additional results from ACTT-2 showed a significant drop in the proportion of patients progressing to noninvasive ventilation, invasive mechanical ventilation, or death. A numerical reduction in mortality risk through day 29 was reported among those treated with baricitinib plus remdesivir.

The study showed a 35% reduction in death among those administered baricitinib plus remdesivir (5.1%) compared with remdesivir monotherapy (7.8%) at day 29 (hazard ratio [HR], 0.65; 95% CI, 0.39-1.08; P = .09). Patients administered oxygen at baseline showed more pronounced decreases in mortality, with group 5 and group 6 patients showing 60% and 43% reduced mortality risks, respectively.

COV-BARRIER compared certain hospitalized patients with confirmed SARS-CoV-2 infection administered baricitinib 4-mg once daily (n=764) with placebo (n=761). Baricitinib was administered for 14 days or until hospital discharge. In the COV-BARRIER study, baricitinib did not achieve the primary end point, but did show a statistically significant reduction in mortality (38%) versus standard of care alone.

Patients administered baricitinib were found to be 2.7% less likely to progress to ventilation (non-invasive or mechanical) or death versus those administered standard of care, which was not deemed statistically significant (odds ratio [OR]: 0.85; 95% CI 0.67, 1.08; P = .1800).

No new safety signals potentially related to baricitinib were identified in the studies.

Baricitinib carries a boxed warning for the risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. Patients treated with the drug have an elevated risk of serious bacterial, fungal, viral, and opportunistic infections leading to hospitalization or death, including tuberculosis.

Higher rates of all-cause mortality and MACE have been observed with another Janus kinase (JAK) inhibitor compared with tumor necrosis factor (TNF) blockers, according to Lilly. Malignancies and thrombosis have been observed in patients administered baricitinib with higher rates found with another JAK inhibitor versus TNF blockers, according to Lilly.

In January, the World Health Organization (WHO) issued a strong recommendation for the use of baricitinib to treat patients with COVID-19. The JAK inhibitor is used to treat rheumatoid arthritis but can also treat individuals with critical or severe COVID-19 in combination with corticosteroids.

The recommendation was based on moderate certainty evidence that baricitinib improves survival and reduces the need for ventilation, with no observed increase in adverse effects. The WHO said that baricitinib has similar effects to interleukin-6 inhibitors, so when both are available, they recommend choosing a treatment based on availability, clinician experience, and cost.

"Nearly 1 million people with COVID-19 have been treated with Olumiant (baricitinib) in approximately 15 countries worldwide," said Patrik Jonsson, Lilly senior vice president, president of Lilly Immunology and Lilly USA, and chief customer officer, in a press release. "Today's full approval reflects both our confidence in Olumiant's role in treating these hospitalized patients and Lilly's tireless efforts to support the medical community and patients in the ongoing fight against COVID-19."

Reference

FDA Approves Lilly and Incyte's OLUMIANT® (baricitinib) for the Treatment of Certain Hospitalized Patients with COVID-19. Eli Lilly and Company. News release. May 11, 2022. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lilly-and-incytes-olumiantr-baricitinib-treatment