Lilly provides comprehensive update on progress of SARS-CoV-2 neutralizing antibody programs
INDIANAPOLIS, Oct. 7, 2020 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced additional details on its SARS-CoV-2 neutralizing antibody programs – including interim data on combination therapy in recently diagnosed patients with mild-to-moderate COVID-19 – and plans to make these therapies broadly available to patients.
"Our teams have worked tirelessly the last seven months to discover and develop these potential antibody treatments," said Daniel Skovronsky, M.D., Ph.D., Lilly's chief scientific officer and president of Lilly Research Laboratories. "We believe the data generated to date provide sufficient evidence that both monotherapy and combination therapy may be effective to treat COVID-19 in patients with a high risk for serious outcomes. Lilly is diligently working with regulators around the world to make these treatments available."
Investors, media and the general public are invited to a conference call today at noon EDT, where Lilly will provide more data and discussion on these programs. The webcast information is available here. A replay will also be available on the website following the conference call.
Combination therapy clinical trial data
The combination therapy significantly reduced viral load at day 11 (p=0.011), meeting the primary endpoint of the study. Most patients, including those receiving placebo, demonstrated near complete viral clearance by day 11. Further, combination treatment reduced viral levels at day 3 (p=0.016) and day 7 (p<0.001)—earlier time points during the course of infection when higher viral loads are typically seen. Combination therapy also significantly reduced the time-weighted average change from baseline from day 1 to 11. An exploratory analysis showed that the proportion of patients with persistent high viral load at day 7 for combination therapy was lower (3.0 percent) versus placebo (20.8 percent), corresponding to a nominal p value of p<0.0001 without multiplicity adjustment. No emergent putative resistance variants have been observed thus far in patients treated with combination therapy.
Combination therapy also met prespecified clinical endpoints, including the time-weighted average change from baseline in total symptom score from day 1 to 11 (p=0.009). The improvement in symptoms was observed as early as three days after dosing and was similar in magnitude and timing to improvements previously seen with LY-CoV555 monotherapy. The rate of COVID-related hospitalization and ER visits was lower for patients treated with combination therapy (0.9 percent) versus placebo (5.8 percent), a relative risk reduction of 84.5 percent (p=0.049). This was also similar to observations for LY-CoV555 monotherapy.
Combination therapy has been generally well tolerated with no drug-related serious adverse events. In LY-CoV555 monotherapy studies there have been isolated drug-related infusion reactions or hypersensitivity that were generally mild (two reported as serious infusion reactions, all patients recovered). Treatment emergent adverse events were comparable to placebo for both LY-CoV555 monotherapy and combination therapy.
Lilly is working to publish the monotherapy and combination therapy data in peer-reviewed journals as soon as possible.
Manufacturing and supply update
To be able to quickly provide treatment to patients around the world, Lilly invested in large-scale manufacturing of both antibodies at risk – even before data demonstrated their potential to become a meaningful therapeutic option for COVID-19.
For monotherapy, Lilly is focused on the 700 mg dose of LY-CoV555 since similar clinical effects were seen across all dose levels tested in BLAZE-1. Lilly anticipates it could supply as many as one million doses of 700 mg LY-CoV555 monotherapy in Q4 2020, with 100,000 available in October. With respect to the supply of combination therapy, Lilly anticipates it will have 50,000 doses available in Q4 2020. The supply of combination therapy will increase substantially beginning in Q1 2021, as additional manufacturing resources come online throughout the year, including Lilly's recently announced manufacturing collaboration with Amgen (NASDAQ: AMGN). Lilly is also pursuing additional partnerships to provide antibodies to resource-limited countries.
Based on the combination therapy data, along with the previously disclosed findings for LY-CoV555 monotherapy, Lilly has engaged global regulators, including the FDA regarding potential EUA. Lilly has now submitted an initial request for EUA for LY-CoV555 monotherapy in higher-risk patients who have been recently diagnosed with mild-to-moderate COVID-19. We expect to submit a subsequent request for EUA for combination therapy in November, pending clinical trial enrollment, once additional safety data accumulate and sufficient supply is manufactured. Lilly anticipates having data to support a biologics license application (BLA) submission for combination therapy as early as Q2 2021. Conversations with global regulators are ongoing.
The BLAZE-1 clinical trial (NCT04427501) continues to enroll a confirmatory cohort of higher-risk patients who have been recently diagnosed with mild-to-moderate COVID-19, testing the ability of the antibody combination to reduce the number of patients with persistent high viral load and reduce COVID-related hospitalizations. In addition, Lilly is studying lower doses of combination therapy and alternative delivery options in planned or ongoing clinical trials. Other ongoing clinical trials include a Phase 3 study of LY-CoV555 monotherapy for the prevention of COVID-19 in residents and staff at long-term care facilities (BLAZE-2, NCT04497987). In addition, LY-CoV555 monotherapy is being tested in the National Institutes of Health-led ACTIV-2 and ACTIV-3 studies of ambulatory and hospitalized COVID-19 patients. Data from these other ongoing trials are not yet available. Thus far, over 850 trial participants have been dosed with LY-CoV555 (alone or in combination with LY-CoV016), contributing to the safety data supporting this potential treatment.
Open-label pragmatic study in COVID-19 outpatients
To generate additional efficacy and safety data, Lilly plans to initiate a pragmatic, open-label study in the coming weeks, enrolling patients treated with either monotherapy or combination therapy, with a focus on collecting data regarding hospitalizations, deaths and safety.
Moving forward, LY-CoV555 and LY-CoV016 will be referred to as bamlanivimab and etesevimab, respectively.
The monotherapy arms of the trial enrolled mild-to-moderate recently diagnosed COVID-19 patients, studying three doses of LY-CoV555 (700 mg, 2800 mg, and 7000 mg) versus placebo. The combination arm of the trial enrolled mild-to-moderate, recently diagnosed COVID-19 patients, studying LY-CoV555 2800 mg plus LY-CoV016 2800 mg versus placebo. Placebo patients were shared across all therapy arms in the completed cohorts.
The primary outcome measure for these completed arms of the BLAZE-1 trial was change from baseline to day 11 in SARS-CoV-2 viral load. Additional endpoints include the percentage of participants who experience COVID-related hospitalization, ER visit or death from baseline through day 29, as well as safety.
The study is ongoing with additional treatment arms. Across all treatment arms, the trial will enroll an estimated 800 participants.
About bamlanivimab (LY-CoV555)
Lilly has successfully completed enrollment and primary safety assessments of LY-CoV555 in a Phase 1 study of hospitalized patients with COVID-19 (NCT04411628) and long-term follow-up is ongoing. A Phase 2 study in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is ongoing. Lilly recently initiated a Phase 3 study for the prevention of COVID-19 in residents and staff at long-term care facilities (BLAZE-2, NCT04497987). In addition, LY-CoV555 is being tested in the National Institutes of Health-led ACTIV-2 and ACTIV-3 studies of ambulatory and hospitalized COVID-19 patients.
About etesevimab (LY-CoV016)
Lilly has successfully completed a Phase 1 study (NCT04441931) of LY-CoV016 in healthy U.S. volunteers to evaluate the safety, tolerability, pharmacokinetics and immunogenicity. LY-CoV016 has been well tolerated and no drug-related severe adverse events (SAEs) have been observed to date.
About Lilly's COVID-19 Efforts
About Eli Lilly and Company
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 LY-CoV555 and LY-CoV016 as a potential treatment 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 future study results will be consistent with the results to date, that LY-CoV555 and LY-CoV016 will prove to be a safe and effective treatment or preventative for COVID-19, that LY-CoV555 and LY-CoV016 will receive regulatory approvals or authorizations, or that we can provide an adequate supply of LY-CoV555 and LY-CoV016 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.
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