A leading Korean biotech venture called Celltrion Group shared recently that preclinical study results of regdanvimab (CT-P59) reveals a neutralizing effect against SARS-COV-2, including the South African variant, in an in vivo model. The early-stage investigational anti-COVID-19 monoclonal antibody treatment at clinically relevant dose materially diminishes SARS-CoV-2 viral loads. The company always had some serious backers: Celltrion’s founder Jung Jin Seo is Korea’s second richest person with a net worth of $12.6 billion. A global Phase 3 study evaluating the monoclonal antibody is led by Korea’s Chungnam National University Hospital.
Reported recently in the preprint server bioRxiv, the Incheon-based biotech company has submitted the manuscript for scientific peer-review and potential publication.
The Investigational Product
CT-P59 was identified as a potential treatment for COVID-19 through screening of antibody candidates and selecting those that showed the highest potency in neutralizing the SARS-CoV-2 virus. In vitro and in vivo preclinical studies showed that CT-P59 strongly binds to SARS-CoV-2 RBD and significantly neutralizes the wild type and mutant variants of concern, including the UK variant (B.1.17). In in vivo models, CT-P59 effectively reduced the viral load of SARS-CoV-2 and inflammation in the lungs. Results from the global Phase I clinical trial of CT-P59 demonstrated a promising safety, tolerability, antiviral effect and efficacy profile in patients with mild symptoms of COVID-19. Celltrion also has recently commenced the development of a neutralizing antibody cocktail with CT-P59 against new emerging variants of SARS-COV-2.
The Preclinical Research
This preclinical study assessed the neutralization effect of CT-P59 against the South African variant, using a clinically relevant dose. CT-P59 demonstrated reduction in the binding affinity against the receptor binding domain (RBD) in the three mutations (K417N, E484K and N501Y substitutions) of the South African variant.
Moreover, CT-P59 exhibits a reduced susceptibility against the South African variant in a live virus and pseudo-virus assay in vitro study. However, there was no significant difference observed in the respiratory viral infection in the upper and lower respiratory tracts when exposed with SARS-CoV-2 wild type and the South African variants in the study. Taken together, the reduced effect in in vitro neutralization of CT-P59 is unlikely to compromise the in vivo therapeutic potency against the variant in the respiratory tract, especially at a clinical dose.
“We are encouraged by the new data, which reinforces that Celltrion’s CT-P59 treatment could be effective against the South African variant and variant mutations,” said Dr. HoUng Kim, Ph.D., Head of Medical and Marketing Division at Celltrion Healthcare. “Faced with the rapid spread of COVID-19 variants, global access to effective antibody treatment is fundamentally important to reduce the disease progression rate to severe COVID-19 and help outpatients avoid hospitalization and alleviate the burden on the health care system. We have commenced the development of a neutralizing antibody cocktail with CT-P59 against new emerging strains in the UK and South Africa and we will continue to further investigate the neutralizing antibodies and other responses to protect against current SARS-CoV-2 strains and emerging variants .”
Celltrion’s global Phase III clinical trial to further evaluate the efficacy and safety of CT-P59 is ongoing in 13 countries, including the U.S., Spain and Romania, having recently completed a patient enrolment of 1,300 people.
The Phase 3 Study
A Phase 3 clinical trial (NCT04602000) was launched late last year and as mentioned spans a number of nations. The study evaluates the safety, tolerability and virology of CT-P59 in patients with mild symptoms of COVID-19.
About the Sponsor
Celltrion Healthcare is committed to delivering innovative and affordable medications to promote patients’ access to advanced therapies. Its products are manufactured at state-of-the-art mammalian cell culture facilities, designed and built to comply with the US FDA cGMP and the EU GMP guidelines. Celltrion Healthcare endeavors to offer high-quality cost-effective solutions through an extensive global network that spans more than 110 different countries. For information about the USA-based operation, see the website.
Yeon-Sook Kim, MD, PhD, Chungnam National University Hospital