Lilly and Incyte announce results from the Phase 3 COV-BARRIER study of baricitinib in hospitalized COVID-19 patients
Randomized, double-blind, placebo-controlled study of 1,525 patients did not meet statistical significance on primary composite endpoint (progression to non-invasive ventilation or invasive mechanical ventilation or death).
Data showed 38% reduction in mortality by Day 28 (nominal p-value=0.0018) in patients treated with baricitinib in addition to standard of care, including corticosteroids and remdesivir.
TORONTO, April 16, 2021 – On April 8, 2021, Eli Lilly and Company and Incyte announced the results of COV-BARRIER, a Phase 3 study evaluating baricitinib 4mg once daily plus standard of care (SoC) versus placebo plus SoC. The trial did not meet statistical significance on the primary endpoint, which was defined as a difference in the proportion of participants progressing to the first occurrence of non-invasive ventilation including high flow oxygen or invasive mechanical ventilation including extracorporeal membrane oxygenation (ECMO) or death by Day 28. Baricitinib-treated patients were 2.7 per cent less likely than those receiving standard of care to progress to ventilation (non-invasive or mechanical) or death, a difference that was not statistically significant (odds ratio [OR]: 0.85; 95% CI 0.67, 1.08; p=0.1800).
In COV-BARRIER, the group treated with baricitinib in addition to SoC (which included 79% receiving corticosteroids and 19% receiving remdesivir, with some receiving both) experienced a significant reduction (nominal p-value=0.0018) in death from any cause by 38 per cent (n/N: 62/764 [8.1%] baricitinib, 100/761 [13.1%] placebo; hazard ratio [HR]: 0.57; 95% CI: 0.41, 0.78) by Day 28. A numerical reduction in mortality was observed for all baseline severity subgroups of baricitinib-treated patients and was most pronounced for patients receiving non-invasive mechanical ventilation at baseline (17.5% versus 29.4% for baricitinib plus SoC versus SoC; hazard ratio [HR]: 0.52; 95% CI: 0.33, 0.80; nominal p-value=0.0065). A reduction in mortality was also seen for the pre-specified subgroups of patients being treated with or without corticosteroids at baseline.
"While we hoped to see a significant benefit on the composite primary endpoint, we were pleased to find a 38 per cent reduction in all-cause mortality by Day 28 in patients treated with baricitinib, the largest reported effect on mortality to date for hospitalized patients with COVID-19", noted Dr. Doron Sagman, vice president, R&D and Medical Affairs, Eli Lilly Canada. "We will continue to evaluate our findings and remain committed to exploring treatment options for COVID-19."
The frequency of adverse events and serious adverse events were generally similar in the baricitinib (44.5% and 14.7%, respectively) and placebo (44.4% and 18.0%, respectively) groups. Serious infections and venous thromboembolism (VTE) occurred in 8.5 percent and 2.7 percent of patients treated with baricitinib, respectively, versus 9.8 percent and 2.5 percent of patients treated with placebo. No new safety signals potentially related to the use of baricitinib were identified.
Lilly intends to publish detailed results of this study in a peer-reviewed journal in the coming months and will share the data from COV-BARRIER with regulatory authorities in Canada, the U.S., European Union and other geographies to evaluate next steps for baricitinib for the potential treatment of hospitalized COVID-19 patients.
COV-BARRIER (NCT04421027) is the first global, randomized, double-blind, placebo-controlled study to assess baricitinib versus placebo in patients hospitalized with COVID-19 receiving SoC which could include corticosteroids, antimalarials, antivirals, and/or azithromycin. This Phase 3 study of 1,525 patients began in June 2020 and enrolled hospitalized patients who did not require supplemental oxygen (ordinal scale [OS] 4), required supplemental oxygen (OS 5) or high-flow oxygen/non-invasive ventilation (OS 6). Patients were also required to have at least one increased marker of inflammation, an indicator of risk of disease progression. All patients were treated with SoC per local clinical practice including 79 per cent receiving corticosteroids (with 91% of those patients receiving dexamethasone) and 19 per cent receiving remdesivir at baseline, with some receiving both. Patients were randomized 1:1 to baricitinib 4mg or placebo for up to 14 days or until discharge from the hospital.
The study was global and included diverse patients from several countries with high prevalence of COVID-19 hospitalizations – the U.S., Brazil, Mexico, Argentina, Russia, India, UK, Spain, Italy, Germany, Japan and Korea. An addendum to the study was initiated in December 2020 to include mechanically ventilated (OS 7) patients at baseline and is currently enrolling.
The COV-BARRIER trial was designed to complement the Adaptive COVID-19 Treatment Trial (ACTT-2) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). ACTT-2 began in May 2020 and has published results from 1,033 patients. Patients who received baricitinib in combination with remdesivir had a shorter median time to recovery compared to patients who received remdesivir alone. In ACTT-2, there was a significant reduction in the proportion of patients progressing to noninvasive ventilation, invasive mechanical ventilation or death, in the baricitinib plus remdesivir group compared to remdesivir. A numerical decrease in mortality risk through Day 29 was observed in patients treated with baricitinib plus remdesivir compared to remdesivir.
Additional research is ongoing to further evaluate the potential role of baricitinib in treating COVID-19, including NIAID’s ACTT-4 trial (evaluating the efficacy and safety of baricitinib or dexamethasone in combination with remdesivir in hospitalized adults with COVID-19 on supplemental oxygen), the RECOVERY trial in the UK and several investigator-initiated trials.
Baricitinib, an oral JAK inhibitor, was discovered by Incyte and licensed to Lilly. It is approved and commercially available as Olumiant in Canada and more than 70 countries as a treatment for adults with moderate- to severe active rheumatoid arthritis (RA).
About Lilly's COVID-19 Efforts
Lilly is bringing the full force of its scientific and medical expertise to attack the coronavirus pandemic around the world. Existing Lilly medicines are being studied to understand their potential in treating complications of COVID-19, and the company is collaborating with partner companies to discover and develop novel antibody treatments for COVID-19. Lilly is testing both single antibody therapy as well as combinations of antibodies as potential therapeutics for COVID-19.
About Olumiant® (baricitinib)
Olumiant is a once-daily, oral Janus Kinase (JAK) inhibitor. In Canada, Olumiant, in combination with methotrexate (MTX), is indicated for reducing the signs and symptoms of moderate- to severe rheumatoid arthritis (RA) in adult patients who have responded inadequately to one or more disease-modifying anti-rheumatic drugs (DMARDs). Olumiant can be used as a monotherapy in cases of intolerance to MTX. 1
In December 2009, Lilly and Incyte announced an exclusive worldwide license and collaboration agreement for the development and commercialization of baricitinib and certain follow-on compounds for patients with inflammatory and autoimmune diseases.
About Lilly Canada
Eli Lilly and Company is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by Colonel Eli Lilly, who was committed to creating high quality medicines that meet people’s needs, and today we remain true to that mission in all our work. Lilly employees work to discover and bring life-changing medicines to people who need them, improve the understanding and management of disease, and contribute to our communities through philanthropy and volunteerism.
Eli Lilly Canada was established in 1938, the result of a research collaboration with scientists at the University of Toronto which eventually produced the world’s first commercially available insulin. Our work focuses on oncology, diabetes, autoimmunity, neurodegeneration, and pain. To learn more about Lilly Canada, please visit us at www.lilly.ca.
For our perspective on issues in healthcare and innovation, follow us on twitter @LillyPadCA and @LillyMedicalCA.
Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Olumiant (baricitinib) as a potential treatment for patients with COVID-19 and reflects Lilly's and Incyte's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of research, development and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date, that Olumiant will receive additional regulatory approvals or authorizations or be commercially successful, or that Olumiant will be safe and effective as a treatment for COVID-19. For further discussion of these and other risks and uncertainties, see Lilly's and Incyte's most recent respective Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly and Incyte undertake no duty to update forward-looking statements to reflect events after the date of this release.
Olumiant Product Monograph, 2020.