EMA issues advice on Lilly’s bamlanivimab (LY-CoV555) alone and administered together with etesevimab (LY-CoV016) for the treatment of confirmed COVID-19 in the European Union

EMA issues advice on Lilly’s bamlanivimab (LY-CoV555) alone and administered together with etesevimab (LY-CoV016) for the treatment of confirmed COVID-19 in the European Union

CHMP has completed a review of available data for both antibodies for the treatment of confirmed COVID-19

CHMP scientific opinion supports national decision-making within European Union (EU) member states on the use of the antibodies during a public health emergency before a formal marketing authorisation is granted

BASINGSTOKE, March 5, 2021 – Eli Lilly and Company (NYSE: LLY) announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive scientific opinion for bamlanivimab alone and bamlanivimab administered together with etesevimab. The opinion advises bamlanivimab alone and bamlanivimab administered together with etesevimab can be used for the treatment of confirmed COVID-19 in patients aged 12 years and older that do not require supplemental oxygen for COVID-19 and who are at high risk of progressing to severe COVID-19. The CHMP scientific opinion under Article 5.3 of regulation 726/2004 provides a harmonized, EU-level opinion on the efficacy, quality, and safety of the antibodies. The opinion can now be considered by the EU member states when making decisions on the use of the therapies at a national level before a formal EU marketing authorization is issued.

“Today's CHMP recommendation is another important milestone in our efforts to extend access to antibody therapies for patients with COVID-19 around the world, providing a pathway for more EU countries to enable use of potentially life-saving treatments for COVID-19. In addition, other countries look to CHMP advice to support their own reviews. We hope this opinion will accelerate those reviews and authorizations, particularly in low- and middle-income countries, where Lilly is prepared to provide doses at greatly reduced costs or free of charge,” said David A. Ricks, Lilly's chairman and CEO. “Lilly is proud that hundreds of thousands of patients globally have already received treatment with our antibody therapy, and we will continue to deliver on our commitment to help high-risk patients who may benefit as the world works to fight this pandemic.”

To support the opinion, the EMA reviewed Phase 2 and Phase 3 results from Lilly’s BLAZE-1 trial. Results from BLAZE-1 demonstrated bamlanivimab alone reduced viral load and symptoms and also reduced COVID-19 hospitalizations by approximately 70 percent, and bamlanivimab and etesevimab together reduced the risk of COVID-19 hospitalizations and death by 70 percent in non-hospitalized high-risk patients with mild to moderate COVID-19.

Lilly Antibody Therapies Around the World

Lilly continues to engage with global regulators regarding the potential of both bamlanivimab alone and bamlanivimab and etesevimab together in treating COVID-19, working with regulators to make these therapies available around the world. The company is focused on areas with the highest disease burden and global allocations are made based on Lilly's guiding principles that aim to ensure access for patients with high unmet need, no matter where they live. Bamlanivimab alone is authorized under special/emergency pathways, in the context of the pandemic, in numerous countries – including Canada, the Czech Republic, Germany, Israel, Italy, Hungary, Sweden, UAE and the U.S. – while bamlanivimab and etesevimab together is currently authorized for emergency use in the U.S. and Italy. In addition, bamlanivimab alone has been authorized for emergency use in Rwanda and Morocco, and through Lilly’s work with the Bill & Melinda Gates Foundation, Lilly is providing doses of the medicine free of charge in these countries.

Important Information about bamlanivimab alone and bamlanivimab and etesevimab together

Bamlanivimab and etesevimab together and bamlanivimab alone have not been approved by the FDA or the EMA for any use. It is not known if bamlanivimab and etesevimab together or bamlanivimab alone are safe and effective for the treatment of COVID-19.

CHMP positive scientific opinion

The opinion advises bamlanivimab alone and bamlanivimab administered together with etesevimab can be used for the treatment of confirmed COVID-19 in patients aged 12 years and older that do not require supplemental oxygen for COVID-19 and who are at high risk of progressing to severe COVID-19.

About bamlanivimab

Bamlanivimab is a recombinant, neutralizing human IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. It is designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially treating COVID-19. Bamlanivimab emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19. Lilly scientists rapidly developed the antibody in less than three months after it was discovered by AbCellera and the scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center. It was identified from a blood sample taken from one of the first U.S. patients who recovered from COVID-19.

Lilly has successfully completed a Phase 1 study of bamlanivimab in hospitalized patients with COVID-19 (NCT04411628). A Phase 2/3 study in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is ongoing. A Phase 3 study of bamlanivimab for the prevention of COVID-19 in residents and staff at long-term care facilities (BLAZE-2, NCT04497987) is also ongoing. In addition, bamlanivimab is being tested in the National Institutes of Health-led ACTIV-2 study in ambulatory COVID-19 patients.

About etesevimab Etesevimab (LY-CoV016, also known as JS016) is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain with high affinity and can block the binding of the virus to the ACE2 host cell surface receptor. Point mutations were introduced into the native human IgG1 antibody to mitigate effector function. Lilly licensed etesevimab from Junshi Biosciences after it was jointly developed by Junshi Biosciences and the Institute of Microbiology, Chinese Academy of Science (IMCAS). Junshi Biosciences leads development in Greater China, while Lilly leads development in the rest of the world.

Lilly has successfully completed a Phase 1 study (NCT04441931) of etesevimab in healthy U.S. volunteers to evaluate the safety, tolerability, pharmacokinetics and immunogenicity. A Phase 2/3 study in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is ongoing. Junshi Biosciences has completed a similar Phase 1 study in healthy volunteers in China and has initiated Phase 1b/2 trials in COVID-19 patients globally.

About BLAZE-1

BLAZE-1 (NCT04427501) is a randomized, double-blind, placebo-controlled Phase 2/3 study designed to assess the efficacy and safety of bamlanivimab alone or bamlanivimab and etesevimab together for the treatment of symptomatic COVID-19 in the outpatient setting. To be eligible, patients were required to have mild or moderate symptoms of COVID-19 as well as a positive SARS-CoV-2 test based on a sample collected no more than three days prior to drug infusion.

In the Phase 2 portion of BLAZE-1, cohorts of mild to moderate recently diagnosed COVID-19 patients, were randomized to one of three doses of bamlanivimab (700 mg, 2800 mg, and 7000 mg), bamlanivimab 2800 mg plus etesevimab 2800 mg, or placebo. Results from the Phase 2 cohorts of BLAZE-1 were published in the New England Journal of Medicine and The Journal of the American Medical Association.

In the Phase 3 portion of BLAZE-1, the combination therapy arms enrolled mild to moderate, recently diagnosed COVID-19 patients who are at high risk for progressing to severe COVID-19 and/or hospitalization, studying bamlanivimab 2800 mg plus etesevimab 2800 mg versus placebo. The primary outcome measure for the Phase 3 portion of the BLAZE-1 trial was the percentage of participants who experience COVID-related hospitalizations or death from any cause by day 29. The key secondary endpoints were change from baseline to day 7 in SARS-CoV-2 viral load, persistently high SARS-CoV-2 viral load on day 7, time to sustained symptom resolution, and COVID-related hospitalization, ER visit or death from any cause from baseline by day 29. Additional endpoints include change from baseline in viral load at other time points, symptom improvement, symptom resolution, as well as safety.

The study is ongoing with additional treatment arms. Across all treatment arms, the trial will enroll up to 3,300 participants.

Adverse Events

Bamlanivimab and etesevimab together

Based on Phase 2 data from BLAZE-1, nausea was the most commonly reported adverse event, reported by 4% of subjects in both bamlanivimab and etesevimab together and placebo groups. Pruritus and pyrexia were more frequently reported from subjects treated with both bamlanivimab and etesevimab (2% and 1%) compared to placebo (1% and 0%, respectively).

Based on Phase 3 data from BLAZE-1, the most common adverse events were nausea, dizziness, and rash. These events each occurred in 1% of subjects treated with bamlanivimab and etesevimab together and in 1% of placebo subjects.

Bamlanivimab alone

Adverse events reported in at least 1% of BLAZE-1 clinical trial participants on bamlanivimab 700 mg alone or placebo were nausea (3% vs 4%), diarrhorea (1% vs 5%), dizziness (3% vs 2%), headache (3% vs 2%), pruritus (2% vs 1%) and vomiting (1% vs 3%).

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 Eli Lilly and Company

Lilly is a global healthcare leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.co.uk

Lilly 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 bamlanivimab (LY-CoV555) alone or bamlanivimab and etesevimab (LY-CoV016) together as potential treatments for patients with COVID-19, as well as its supply and distribution, and reflects Lilly's current beliefs and expectations. However, as with any such undertaking, there are substantial risks and uncertainties in the process of drug development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date, that bamlanivimab alone or bamlanivimab and etesevimab together will prove to be safe and effective treatments or successful preventative therapies for COVID-19, that bamlanivimab alone or bamlanivimab and etesevimab together will receive regulatory approvals or additional authorizations, or that Lilly can provide an adequate supply of bamlanivimab alone or bamlanivimab and etesevimab together in all circumstances. For a further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, please see Lilly's most recent Forms 10-K and 10-Q filed with the U.S. Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.