Celltrion: Infliximab Biosimilar Shows Promise for COVID-19

The Center for Biosimilars spoke with Byoungseo Choi, head of marketing for Celltrion Healthcare, a company very active in the biosimilar space. In part 1 of this interview, Senior Editor Tony Hagen asks Choi about Celltrion's infliximab biosimilar (Inflectra, Remsima) and how it may aid in the treatment of coronavirus disease 2019 (COVID-19)—related inflammation. Choi also talks about the company’s ambitious plans to launch 1 new biosimilar each year through 2030.

Below is a list of the questions that were provided to Celltrion in advance of the interview, along with Choi’s responses.

Topic: Celltrion’s work toward finding treatments helpful with COVID-19.

1. Regarding participating in the CATALYST trial, how did Celltrion’s infliximab come to be picked, and what does the evidence suggest so far to indicate that CT-P13 (Inflextra, Remsima) has value in bringing down cytokine release syndrome (CRS)?

Sir Marc Feldmann and Professor Duncan Richards (Oxford Clinical Trials Unit), Dr Matthew Rowland (ICU), and colleagues published a Lancet paper describing how infliximab could be used to treat COVID-19. As a result, Celltrion Healthcare reached out to Sir Marc and his associates to discuss collaborating on a trial of infliximab for COVID-19.

We are now partnering with the University of Oxford and University Hospitals Birmingham on an arm of the CATALYST trial to understand if the use of CT-P13 (biosimilar infliximab) could accelerate the recovery of patients with COVID-19.

Emerging evidence is demonstrating a critical role for anti-inflammatory drugs in the cytokine storm associated with severe COVID-19 infection. CT-P13 has been used for several years in the treatment of multiple inflammatory conditions, which makes it a good candidate for trialing in the treatment of COVID-19 due to its widespread availability and well-established safety profile.

Findings from various medical sources show that anti-tumor necrosis factor (TNF) therapies such as infliximab could be a potential option in COVID-19:

• In a registry of people with rheumatic disease who were diagnosed with COVID-19, anti-TNF use was associated with the reduced odds of hospitalization (OR 0.40, 95% CI 0.19 to 0.81).
• According to an Italian case report of an adult patient with severe ulcerative colitis (UC) and COVID-19, after 7 days on infliximab, the patient’s intestinal symptoms and general well-being had markedly improved. This patient with severe UC and COVID-19 was successfully treated for both conditions with infliximab.

2. Celltrion earlier this year announced intentions to start human trials of therapeutic antibodies for neutralizing the COVID-19 virus. How does this effort differ from the CT-P13 CATALYST involvement and where does it stand currently?

In terms of clinical initiatives, we are in the process of developing an antiviral treatment specific to COVID-19 and a super-antibody effective against new strains. As there is evidence of inflammatory excess in patients with COVID-19, we are also working toward a trial that will investigate the use of infliximab as a potential second-line treatment alongside administration of an antiviral.

Whilst the CATALYST trial aims to show that our drug could delay or prevent the rapid deterioration into intensive care for hospitalized patients, our antiviral antibody treatment aims to prevent the infection and proliferation of COVID-19. However, both involvements are for the same objective: to bring our full resources and expertise to overcome this global health crisis and dedicate our efforts to support health care systems across the world

Celltrion recently announced a positive preclinical result for its COVID-19 antiviral antibody treatment, which showed improvement in recovery time in an animal model and anticipates starting the first in-human clinical trials in July.

3. The company has stated that it is not pursuing therapeutic antibody treatments for profit, but to contribute to the global effort to defeat COVID-19. Please discuss this altruism against shareholder perspectives and expectations.

Celltrion Group was among the first that have embarked on the development of a therapeutic antibody treatment and diagnostic kits on the onset of the global spread of the novel coronavirus, in a bid to contribute to stopping what would escalate into the coronavirus pandemic.

As Celltrion Group Chairman Seo Jung-jin has said earlier, the development of these solutions is driven by our commitment to placing the public interest before our own. Simply put, we are acting on our responsibility as a member of the global pharmaceutical community as we willingly step forward to help address the global coronavirus pandemic.

Facing uncertain times during this coronavirus pandemic, we are in line with our shareholders’ perspectives/expectations to create shared value. By addressing the societal needs by developing a treatment, we can expand in the markets in ways that benefit society and shareholders simultaneously while creating value for our customers, communities, and ultimately our investors.

We advise our investors to understand that our efforts to develop a coronavirus treatment and diagnostic kits are not commercially motivated, and their investment decisions should be made based on our business records and the underlying value of our product portfolio.

4. Please say a few words about supply chain issues during the pandemic and how Celltrion has responded to secure active pharmaceutical ingredients and ensure that its products reach market.

To tackle the concerns regarding any expected supply chain issues during the pandemic, Celltrion has run a contingency plan considering each government’s response to the ever-changing situation and all available distribution options.

Furthermore, Celltrion has been closely working with our partners in global locations and closely monitoring inventory levels and distribution channels to plan ahead for maximum manufacturing capacity.

We have thus secured adequate stocks of our products to avoid any disruption in our supply chain.

Topic: The company has announced intentions to launch 1 biosimilar per year through 2030. This is a very ambitious schedule.

What’s going to be needed to make this happen? Please talk about the strong European sales network you hope to establish.

We have now set up our own sales network and overseas subsidiaries in 14 countries throughout Europe to secure competitiveness of our products. Starting with Germany, the United Kingdom, and the Netherlands, we have started launching the new subcutaneous infliximab country by country by establishing local operations across major European countries, building our commercial capabilities and strengthening our relationships with stakeholders across these markets

In order for the market to continue to grow, we need the following:

a. Competitive price

As competition increases, attaining low costs is critical for biosimilar manufacturers to support discount and defend against competition. The biosimilar industry needs to keep reducing production and distribution costs to set the price competitive. With this in mind, Celltrion Healthcare is working on a titer improvement and high concentration formulation to maximize the price merit.

b. Added Value

The industry should plan to not only develop biosimilars, but also to add value to medicines by developing bioinnovatives (biobetters) and new medicines that offer enhanced properties, ie, enhanced patient convenience of use. Essentially, biologics are moving toward personalized medicines. In this sense, Celltrion anticipates that Remsima SC will offer stable potency and low immunogenicity compared with the IV formulation as well as increased flexibility and convenience through self- administration.

In Part 2 of this interview, Choi continues the discussion of the company’s biosimilar pipeline, discusses the competitive landscape for its products, especially adalimumab, and talks about Celltrion’s plans to build a biosimilar production center in Wuhan, China.