Combination Study with JS016 and LY-CoV555 for Patients with Mild-to-Moderate COVID-19 Symptoms Met Primary and Secondary Endpoints
- Viral load, symptoms, and hospitalizations orERvisits reduced
- Request for EUA and BLAfilingsfor the combination therapy anticipated in Nov 2020 and as early as 2Q2021, respectively
- Large scale open-label study planned in coming weeks
SHANGHAI, China, Oct. 08, 2020 (GLOBE NEWSWIRE) -- Junshi Biosciences (HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies, announced today that its global partner Eli Lilly and Company announced positive interim data on combination therapy with neutralizing antibodies JS016 (LY-CoV016) and LY-CoV555 in recently diagnosed patients with mild-to-moderate COVID-19 illness. Lilly intends to submit a request for Emergency Use Authorization (EUA) for the combination therapy in patients with mild-to-moderate COVID-19 in November 2020.
Data from a new interim analysis of Lilly sponsored BLAZE-1 clinical trial showed that combination therapy with two SARS-CoV-2 neutralizing antibodies reduced viral load, symptoms and COVID-related hospitalization and ER visits. The randomized, double-blind, placebo-controlled Phase 2 study evaluated JS016 (LY-CoV016) and LY-CoV555 (from Lilly’s collaboration with AbCellera), which bind complementary regions of the SARS-CoV-2 spike protein, for the treatment of symptomatic COVID-19 in the outpatient setting. The combination cohort enrolled recently diagnosed patients with mild-to-moderate COVID-19, who were assigned to 2800 mg of each antibody (n=112) or placebo (n=156).
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 time-weighted average change from baseline from day 1 to 11. An exploratory analysis showed that the proportion of patients with persistently 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 3 days after dosing. 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).
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 data from the study in peer-reviewed journals as soon as possible.
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 expects to submit a 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 persistently 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.
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, JS016 (LY-CoV16) and LY-CoV555 will be referred to as etesevimab and bamlanivimab, respectively.
BLAZE-1 (NCT04427501) is a randomized, double-blind, placebo-controlled Phase 2 study designed to assess the efficacy and safety of JS016 and LY-CoV555 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 3 days prior to drug infusion.
The combination arms of the trial enrolled mild-to-moderate, recently diagnosed COVID-19 patients, studying JS016 2800 mg plus LY-CoV555 2800 mg versus placebo.
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.
About etesevimab (JS016)
JS016 (also known as LY-CoV016) 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 effectively 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. A SARS-CoV-2 challenge study was conducted in the rhesus macaques and showed LY-CoV016 is effective for both prophylactic and therapeutic venues against SARS-CoV-2 infection. Lilly licensed JS016 from Junshi Biosciences after it was jointly developed by Junshi Biosciences and 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 JS016 in healthy U.S. volunteers to evaluate the safety, tolerability, pharmacokinetics and immunogenicity. Junshi Biosciences has completed a similar Phase 1 study in healthy volunteers in China and has initiated Phase Ib/II trials in COVID-19 patients globally. Junshi Biosciences also intends to investigate the prophylactic potential of JS016 in high-risk population soon. JS016 has been well tolerated and no drug-related severe adverse events (SAEs) have been observed to date.
About bamlanivimab (LY-CoV555)
LY-CoV555 is a potent, neutralizing 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 preventing and treating COVID-19. LY-CoV555 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 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 Junshi Biosciences
Founded in December 2012, Junshi Biosciences (HK: 1877; SH: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapeutics. The company has established a diversified R & D pipeline comprising 26 innovative drug candidates and 2 biosimilars, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurologic, and infectious diseases. Junshi Biosciences was the first Chinese pharmaceutical company that obtained marketing approval for PD-1 monoclonal antibody in China and clinical trial application approval for anti PCSK9 monoclonal antibody from NMPA. The world’s first in human anti-BTLA antibody for solid tumors was officially approved for clinical trials by the FDA and NMPA. From this year onwards, Junshi Biosciences pooled its efforts with Chinese science institutions to co-develop JS016, China’s first neutralizing human monoclonal antibodies against SARS-CoV-2, that has entered clinical trial, part of our continuous innovation for disease control and prevention in China and beyond. We have about 2,000 employees in San Francisco and across Maryland in the United States, as well as Shanghai, Suzhou, Beijing, and Guangzhou, China. For more information, please visit: http://junshipharma.com.
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 www.lilly.com and www.lilly.com/news.
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