Looking to the Future, Biosimilar Pioneer Celltrion Is Banking on Biobetters

Republic of Korea—based biosimilar developer Celltrion has been a pioneer in the biosimilars field, with its flagship product, CT-P13 (an infliximab biosimilar sold as Inflectra in the US market and Remsima in other regulatory territories), having captured more than half of the European market for infliximab as of late last year and having gathered a wealth of data demonstrating safety and efficacy in real-world treatment of inflammatory diseases. But will CT-P13’s future be as a “biobetter?”

During a keynote speech given today at the FT Global Pharmaceutical and Biotechnology Conference in London, United Kingdom, Sang Joon Lee, PhD, senior executive vice president of Celltrion, said that in the increasingly competitive and dynamic environment of biosimilars, companies need to innovate in order to survive. Biosimilar developers can seek to stand out through value-added services, but improvements in products themselves—ones that may give them an advantage such as lower immunogenicity or a new route of administration—may be the key to unlocking a better patient experience.

Celltrion seeks to provide just such an improvement with a novel subcutaneous formulation of CT-P13 that can differentiate the product from an increasing number of biosimilar infliximab contenders. The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use recently issued a positive opinion for the subcutaneously administered version of the drug in the indication of rheumatoid arthritis (RA), and in the US context, Celltrion has also begun recruiting patients for a phase 3 clinical trial of the subcutaneous biosimilar with an eye toward FDA approval in inflammatory bowel disease.

According to Lee, one clear benefit of the subcutaneous route of administration for the drug is that it allows patients a level of independence to administer their therapy and eliminates the need for lengthy chair time for infusions, as well as time-consuming travel to and from infusion centers. That reduced burden on the patient may well help with patient compliance, and while no price has yet been set for the product, it could also help reduce costs.

However, the subcutaneous product also has other advantages: According to Lee, the subcutaneous option provides lower immunogenicity and a higher maintained peak serum concentration. Data being presented this week at the American College of Rheumatology’s 2019 annual meeting in Atlanta, Georgia, also demonstrate that patients with active RA can be safely switched from the intravenous biosimilar to the subcutaneous option.¹

Despite these advantages that could make the product a commercial success, one particular challenge for developing a biobetter of an existing biosimilar is that no regulatory framework exists to handle these drugs. In the European Union, the EMA allowed Celltrion to seek an expanded authorization for CT-P13 in its new formulation as a line extension, but in the US context, the FDA has required that the company submit the product as a new drug.

Speaking to The Center for Biosimilars^® in a press briefing following the keynote, Lee said that submitting a new application for the product is an extremely costly proposition. However, Celltrion sees an opportunity in the market to compete with other subcutaneously administered products, such as brand-name etanercept (Enbrel) and adalimumab (Humira), which could make the costly regulatory undertaking well worthwhile.

In fact, pursuing biobetters may even prove to be more important for Celltrion than pursing interchangeable biosimilars. Lee told The Center for Biosimilars^® that pursuing an interchangeable designation from the FDA can also be an expensive process, given the need for potentially lengthy clinical trials. Given that the company would stand to gain just 1 year of market protection from securing an interchangeable designation, and given the fact that the United States is only one market in which the company sells its biosimilars, it is not yet clear to Lee that pursuing interchangeability is worthwhile, though the company did issue a statement in July asking the FDA for more clarity about the agency's guidance on interchangeability.

With respect to some of Celltrion’s other products, Lee said that Celltrion’s proposed omalizumab biosimilar, CT-P39, currently in phase 1 development, has a clinical trial design that is intended to be able to support an interchangeable designation, but the company has not yet made a determination of whether it will pursue that avenue with the FDA.

Looking to the future, said Lee, the company is also pursuing a pipeline of biosimilars and novel therapeutics, including monoclonal antibodies and antibody-drug conjugates.

Reference

1. Westhovens R, Wiland P, Zawadzki M, et al. Efficacy and safety of a novel subcutaneous formulation of CT-P13 over the 1-year treatment period and after switching from intravenous CT-P13 in patients with active rheumatoid arthritis: results from part 2 of phase I/III randomized controlled trial. Presented at: The American College of Rheumatology Annual Meeting; November 8-13, 2019; Atlanta, GA. Abstract 548.