Junshi Biosciences (HK: 1877; SHA: 688180) and Eli Lilly (NYSE: LLY) announced their dual mAb treatment was approved in the US to treat COVID-19 under emergency use rules. In a US Phase II/III trial, a combination of Junshi's etesevimab (JS016) and Lilly's bamlanivimab (LY-CoV555) reduced the risk of COVID-19 hospitalizations and death by 70% in newly diagnosed patients. It is indicated for patients with mild to moderate COVID-19 aged 12 and older who are at high risk for progressing to severe COVID-19 and/or hospitalization.

Junshi's etesevimab (JS016 or 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. It is designed to 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 after it was jointly developed by Junshi and the Institute of Microbiology, Chinese Academy of Science (IMCAS). Junshi leads development in Greater China, while Lilly leads development in the rest of the world.

The US approval said etesevimab and bamlanivimab should be administered together via a single intravenous infusion as soon as possible after a positive COVID-19 test and within 10 days of symptom onset. The FDA also allowed infusion times for bamlanivimab alone and the bamlanivimab/etesevimab combination to be as short as 16 or 21 minutes, respectively, down from the previously authorized time of 60 minutes.

The EUA is based on Phase III data from the BLAZE-1 trial, announced on January 26, 2021, which replicated earlier results, published in The Journal of the American Medical Association (IF=45.54), in a much larger group of patients. The most common adverse event most often reported for patients in the active arm was nausea on the day of infusion.

Although Phase II and III trials evaluated a range of doses of bamlanivimab alone and etesevimab/bamlanivimab in combination, data showed consistent and similar clinical effects among all doses studied. In addition, initial results from an ongoing Phase II study produced viral load and pharmacodynamic/pharmacokinetic data that demonstrated etesevimab 1400 mg and bamlanivimab 700 mg together produced similar effects to the results from the Phase III trial with etesevimab 2800 and bamlanivimab 2800 together. Together, these data provide confidence in the reduced dose, which expands available supply to help more patients without sacrificing potential efficacy.

Lilly's bamlanivimab alone is authorized in numerous countries, while bamlanivimab and etesevimab together is currently authorized in the US and Italy. Lilly will continue working with global regulators to make these therapies available around the world. In an effort to help as many patients as possible, Lilly will continue to accelerate manufacturing of etesevimab for use around the world. In collaboration with Amgen, Lilly plans to manufacture up to 1 million doses of etesevimab for administration with bamlanivimab by mid-2021.

Lilly said it has 100,000 doses ready immediately and another 150,000 doses will be available during the first quarter.

Dr. Ning Li, CEO of Junshi Biosciences said: “Since the outbreak of the pandemic, Junshi Biosciences and the IMCAS have been dedicated to the co-development of neutralizing antibodies. Now, with Lilly, our global partner’s participation, the innovative therapy is authorized for use in the U.S. and Italy, while unremitting endeavors to meet the extensive anti-COVID-19 needs are made by the local and overseas medical industry."

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.

Lilly's bamlanivimab (LY-CoV555) 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 that prevent and treat 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.

Founded in December 2012, Junshi has established a diversified R&D pipeline comprising 27 innovative drug candidates and 2 biosimilars, with five therapeutic focus areas: cancer, autoimmune, metabolic, neurological, and infectious diseases. Junshi Biosciences was the first China pharma approved to launch its anti-PD-1 monoclonal antibody in China.

In early 2020, Junshi joined forces with the Institute of Microbiology Chinese Academy of Science and Eli Lilly to co-develop JS016, China’s first neutralizing fully human monoclonal antibody against SARS-CoV-2.  

See our other articles on Junshi and Lilly.

Disclosure: none.