COVID-19: Celltrion’s therapeutic option

In just over a year, Celltrion Healthcare says it has identified and delivered a potential treatment for COVID-19. pharmaphorum spoke to Kwon Ki-sung, Head of Celltrion’s R&D unit, to learn more.

Celltrion’s COVID-19 therapeutic, CT-P59, is a monoclonal antibody (mAb) with activity against COVID-19. It was identified as a potential treatment through the screening of antibody candidates from recovered patients and selecting those that showed the highest potency in neutralising the SARS-CoV-2 virus. It is designed to treat mild-to-moderate COVID-19 in adults who have tested positive and are at high risk of progressing to severe COVID-19 and or hospitalisation.

Celltrion’s previous experience in developing therapeutic antibodies enabled the company to act with speed as the COVID-19 pandemic hit.

“As a company, we felt well-placed to develop a therapeutic option against COVID-19 as we have experience in developing therapeutics for similar viruses,” says Ki-sung. “We have completed phase 2 trial of a multi-antibody drug for influenza, CT-P27, and since 2015 we have been developing a therapeutic antibody to treat the Middle East Respiratory Syndrome (MERS), CT-P38. As soon as the COVID-19 outbreak began, we implemented an emergency preparedness plan which leveraged this experience and our unique antibody discovery, development and manufacturing processes to identify a potential treatment.”

Overcoming obstacles

It typically takes years of investment to develop a new antibody treatment. COVID-19 was quickly declared a public health emergency, therefore Celltrion had to shorten the development timeframe and expedite regulatory procedures.

“This really tested pharmaceutical companies,” explains Ki-Sung. “All of our processes, and also those of the entire healthcare ecosystem, including regulators, had to be accelerated. We found that strong and open channels of communication were imperative. Ensuring that we were keeping all teams and stakeholders updated on progress helped to avoid any potential misunderstandings and subsequent delays.”

In addition to time pressures, the pandemic exacerbated some of the challenges associated with conducting global clinical trials, including patient recruitment and retention, social distancing measures causing restrictions on patients’ ability to visit trial sites and many more.

“We leveraged our ample experience in conducting global clinical trials in the field of monoclonal antibody biosimilar and designed the clinical trial for CT-P59 according to its mechanism of action of a monoclonal antibody to treat COVID-19 patients in early stages.”

The company remained in close and frequent communication with regulatory agencies to accelerate procedures for the evaluation and authorisation of the clinical trials.

The result was that Celltrion was able to demonstrate the safety of CT-P59 in healthy volunteers, its efficacy in a phase 2 trial and the statistical safety and efficacy in a large-scale global phase 3 trial.

According to recently announced top-line results from global Phase 3 trial, CT-P59 significantly reduced the risk of COVID-19 related hospitalisation or death by 72% for patients at high- risk of progressing to severe COVID-19 and 70% for all patients. In addition, patients who were treated with CT-P59 reported a significantly shortened time to clinical recovery by at least 4.7 days for patients at high- risk of progressing to severe COVID-19 and by 4.9 days compared to placebo for all patients.

“All of our processes, and also those of the entire healthcare ecosystem, including regulators, had to be accelerated. We found that strong and open channels of communication were imperative” 

Acting with agility  

Within a year, Celltrion received conditional marketing authorisation for CT-P59 from the Korean Ministry of Food and Drug Safety (MFDS), leveraging the company’s experience in developing mAbs and new drugs. Strong leadership has been integral in enabling the company to be so agile according to Ki-sung.

“Our innate, agile work culture has driven innovation and transformed the company into a passion- driven powerhouse. We’ve had strong and consistent leadership and high-level management support throughout the entire pandemic who have led by example, encouraging us to be agile and resilient. This leadership, coupled with our hard-working and dedicated teams of staff across the entire Celltrion group working 24/7 shifts, enabled us to achieve so much in such a short period of time through agile working,” explains Ki-sung.

Managing the regulatory process

Celltrion has submitted data on quality and manufacturing process management, non-clinical and clinical trials to the European Medicines Agency (EMA) as part of a rolling review of CT-P59. Based on this comprehensive data package, Celltrion is now working closely with the EMA to complete the rolling review process and received positive scientific opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) in March 2021.

“This means the treatment can be used in the European Union to treat COVID-19 in patients who do not require supplemental oxygen and who are at high risk of their COVID-19 disease becoming severe,” explains Ki-sung.

Celltrion is also in discussion with regulatory authorities in other regions including the U.S. Food and Drug Administration and plans on submitting data against SARS-CoV-2 variants to accelerate the approval process of regulatory authorities.

“We remain committed to assessing the therapeutic neutralizing antibodies against a wide array of emerging variants to help end the pandemic. CT-P59 has already demonstrated neutralizing capability against key emerging mutations, including SARS-CoV-2 variants first identified in New York (B.1.526), Nigeria (B.1.525), Brazil (Gamma, P.1) and South Africa (Beta, B.1.351). The company also recently announced preclinical study results of CT-P59 against the Delta variants (B.1.617.2, formerly ‘Indian’ variant) in July. New results from an in vivo efficacy study showed that CT-P59 has a strong neutralising effect against the rapidly spreading Delta variant. We remain encouraged by these findings, which reinforce our confidence that CT-P59 should be protective against these variants,” says Ki-sung.

Learnings for the future

The pandemic has no doubt changed the future of healthcare. But, what will companies like Celltrion take forward?

“We look forward to taking the invaluable experience gained throughout this pandemic into the future. Whilst it has no doubt been challenging, it’s strengthened us as a team and our operational processes, and we feel better prepared to be able to tackle and handle any future pandemics,” says Ki-sung.

“We also believe that this will have a positive impact on our current product pipelines that are under development and are in the clinical trial phase. We are committed to bringing treatment to people living with other serious and life-threatening diseases, so will ensure that we leverage the progress we’ve made due to COVID-19 to bring treatments to more people in need.”