Lilly Statement on the NIAID Decision to Pause Enrollment in ACTIV-3 Clinical Trial

READ: Lilly's update to this statement about the ACTIV-3 clinical trial

+ ACTIV-3 is an independent, NIH-sponsored study in hospitalized patients testing bamlanivimab (LYCoV555) in combination with remdesivir

+ Independent data safety monitoring board (DSMB) recommended pause

+ Pause impacts the ACTIV-3 study of a Lilly neutralizing antibody; all other studies continue

+ Lilly’s other ongoing studies focus on earlier stages of COVID-19 disease or prophylaxis

Since the beginning of the COVID-19 pandemic, Lilly has brought the full force of our scientific capabilities to fight this new disease, collaborating with the U.S. government and industry partners to discover potential treatments. Together, we have sought to learn about the potential impact of neutralizing antibodies across the broadest set of patients even as we were still evolving in our understanding of SARS-CoV-2 virus pathology. As always, we have remained deeply committed to patient safety.

What We Know Now

As of last evening, Lilly continued to be in communication with the trial sponsor regarding the recommendation from the independent data safety monitoring board (DSMB) of the ACTIV-3 clinical trial to pause enrollment of the study. ACTIV-3, which is evaluating Lilly’s investigational neutralizing antibody bamlanivimab (LY-CoV555) as a treatment for COVID-19 in hospitalized patients, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

At this time, only the DSMB has reviewed the data from the trial, and NIH leadership and Lilly remain blinded to the ongoing trial results. Lilly trusts the judgment of the independent DSMB and supports its decisions to exercise caution in ensuring the safety of the patients participating in this study.

Importantly, the DSMB also considered the impact of the ACTIV-3 study pause on ACTIV-2 and did not recommend any changes to that study’s design or enrollment.

What Differentiates ACTIV-3 from Other Bamlanivimab Studies

The ACTIV-3 clinical trial is the only ongoing study evaluating the efficacy of Lilly’s neutralizing antibody in hospitalized COVID-19 patients, the most advanced stage of the disease. The dose of bamlanivimab being investigated in this trial is 7000 mg.

Individuals in the ACTIV-3 study have been infected with the virus for a longer period of time and may have more severe symptoms than patients studied in other bamlanivimab trials. Hospitalized patients receive different treatments for COVID-19 than earlier stage patients, including treatment with the antiviral medicine remdesivir.

For these reasons, hospitalized patients may have less benefit from neutralizing antibodies, which are a supplement to the patients’ own immune system, as they may have developed their own endogenous antibody response and be in a phase of disease characterized by inflammatory responses to virus. This is why the use of immunosuppressive treatments is both widespread and still being investigated in hospitalized patients.

Lilly’s Neutralizing Antibody Development Program

Lilly is testing both single antibody therapy, as well as combinations of antibodies as potential therapeutics for COVID-19, across two different patient populations.

Lilly’s development program includes:

• BLAZE-1, an ongoing Phase 2 study in people recently diagnosed with COVID-19 in the ambulatory setting (NCT04427501). This trial is testing both bamlanivimab alone and in combination with a second antibody (etesevimab, LY-CoV016)

• BLAZE-2, a Phase 3 study of bamlanivimab for the prevention (prophylaxis) of COVID-19 in residents and staff at long-term care facilities (NCT04497987)

• Bamlanivimab is also being tested in the NIH-led ACTIV-2 study in recently diagnosed mild to moderate COVID-19 patients.

These trials are not affected by the enrollment pause in the NIH-sponsored trial of hospitalized patients.

The population where Lilly has efficacy data for neutralizing antibodies is in recently diagnosed mild to moderate COVID-19 illness in high-risk patients. In this population, we also have a large safety database inclusive of over 480 drug-treated patients across a broad dose range and have reported a potential benefit in clinical outcomes with a reduction in viral load and rates of symptoms and hospitalizations. In the BLAZE-1 trial, rates and types of adverse events were similar between bamlanivimab and placebo, with the majority being mild to moderate in severity and with no drug-related serious adverse events reported thus far. In other bamlanivimab studies, there have been isolated drug-related infusion reactions or hypersensitivity that were generally mild (two reported as serious infusion reactions, both patients recovered).

Next Steps

The scientific development process is challenging and unpredictable. It takes collaboration and commitment from scientists, researchers, patients, and companies across the biopharmaceutical industry to discover and develop treatments for diseases such as COVID-19. Every trial, no matter what it reveals, advances medical science and understanding – ultimately bringing new solutions one step closer to reality.

While we await additional data to help us understand whether neutralizing antibodies could play a role in helping hospitalized patients, we remain confident in the potential benefits of neutralizing antibodies in patients earlier in the disease course of COVID-19. We are grateful to the patients, physicians, and staff who have participated in our ongoing clinical trials. We continue to believe that the data generated in those clinical studies could support both the therapeutic benefits and safety profile of our neutralizing antibody in ambulatory patients and in prophylaxis.

Lilly Cautionary Statement Regarding Forward-Looking Statements

This statement contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Lilly’s neutralizing antibodies bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016) as potential treatments for patients with or at risk of infection from COVID-19 and reflects Lilly's current beliefs. 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 studies will complete as planned, that future study results will be consistent with the results to date, that bamlanivimab and etesevimab will prove to be safe and effective treatments or preventatives for COVID-19, that bamlanivimab and etesevimab will receive regulatory approvals or authorizations, or that we can provide an adequate supply of bamlanivimab and etesevimab 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.