Celltrion Will Sell World's First Subcutaneous Infliximab Directly In Europe
Executive Summary
Celltrion has set out plans to market directly its subcutaneous version of infliximab in Europe. The firm has just received a nod that sets the stage for approval across the EU, albeit with more limited indications than the existing intravenous version.
Celltrion has set out plans to market directly in Europe its subcutaneous version of biosimilar infliximab, after it received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use. The originator product, Janssen's Remicade, does not come in a subcutaneous formulation, although rival anti-TNF inhibitors including Humira (adalimumab) and Cimzia (certolizumab), do.
While Celltrion’s Remsima version of infliximab is already authorized in the EU as a 100mg powder for concentrate for solution for infusion, the CHMP has recommended changing the terms of the marketing authorization to add a 120mg solution for injection for subcutaneous use in prefilled pens or syringes.
However, whereas intravenous Remsima is authorized for psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, psoriasis, Crohn’s disease and rheumatoid arthritis, the CHMP highlighted that “Remsima for subcutaneous use is authorized only in the rheumatoid arthritis indication.”
The full indication for the subcutaneous pens and syringes covers treating rheumatoid arthritis in adult patients with active disease, when the response to disease-modifying anti-rheumatic drugs has been inadequate; and in adults with severe, active and progressive disease not previously treated with methotrexate or other DMARDs. “In these patient populations,” the CHMP noted, “a reduction in the rate of the progression of joint damage, as measured by x-ray, has been demonstrated.”
Seeking Expanded Indications After Further Tests
Celltrion noted that the positive CHMP opinion was based on a Phase I/III study to evaluate pharmacokinetics, efficacy and safety between the subcutaneous and intravenous versions of its infliximab in patients with active rheumatoid arthritis. (Also see "Celltrion Reports Positive Rheumatoid Arthritis Data From Subcutaneous Infliximab" - Generics Bulletin, 20 Jun, 2019.)
The positive CHMP opinion “brings us one step closer to providing a personalized treatment approach for people living with rheumatoid arthritis,” commented vice-chairman of Celltrion Healthcare, Hyoung-Ki Kim. “This marks an important milestone for our business providing people with a new route of administration, and a novel formulation of infliximab. If approved, we will begin a new era in the biotherapeutic class, as [subcutaneous Remsima] would be the world’s first subcutaneous version of infliximab, expanding treatment options for physicians and their patients.”
In particular, Celltrion noted, “a subcutaneous formulation has the potential to enhance treatment options for the use of biosimilar infliximab by providing high consistency in drug exposure and a convenient method of administration,” as well as reducing the time spent in hospital for intravenous treatment.
Commenting on the CHMP nod – and the more limited label of subcutaneous Remsima compared to the intravenous version – biosimilars specialist Duncan Emerton, director at Informa Pharma Consulting, noted that extrapolation of indications “does not apply in this case.”
This was due to the lack of an original subcutaneous version of infliximab for Celltrion’s version to refer to, he explained. “You cannot get extrapolation from a product that does not exist.”
The hurdle for Celltrion, Emerton suggested, would be getting approval for all the desired indications, based on individual studies for the subcutaneous version.
More Studies Already Under Way
A Phase III study of subcutaneous Remsima for people with inflammatory bowel disease is already underway, Celltrion noted, confirming that it would “seek expanded indications following the results of this trial.”
Earlier this year, Celltrion presented data demonstrating that the subcutaneous formulation of Remsima was comparable in terms of efficacy and safety with the intravenous formulation for the treatment of Crohn’s disease. (Also see "Celltrion’s Subcutaneous Infliximab Shows Promise" - Generics Bulletin, 12 Mar, 2019.)
And last month, Celltrion told Scrip that it was pursuing the same indications for the subcutaneous formulation as for Janssen’s Remicade reference product in both Europe and the US. The Korean firm has started recruiting patients for a Phase III study using the subcutaneous form in the US after the US Food and Drug Administration permitted it to skip Phase I and II trials on the strength of the European data. (Also see "Celltrion Begins US Phase III For Infliximab SC, Aims For 2022 Launch " - Scrip, 2 Aug, 2019.)
Celltrion Will Market Remsima SC Directly
The South Korean firm has also set out plans to take a different approach to commercializing this product, compared to previous biosimilar launches, which have largely been built on alliances with local partners, especially in individual European markets.
“Celltrion Healthcare will adopt a different business strategy for [subcutaneous Remsima], compared to strategies for previous products in the portfolio,” the firm said, “and is considering both direct and indirect sales based on the optimal model in each local country.”
Pressed further on commercialization plans, Celltrion told Scrip that the firm is planning to sell subcutaneous Remsima directly, beginning in Europe. As such, the company said it was now establishing direct sales networks in European countries in line with the EMA approval schedules. Typically, the European Commission acts on centralized CHMP recommendations within 67 days.
Celltrion’s direct marketing plans tie in with the broad business plan announced by Celltrion Group earlier this year.
At the start of 2019, Celltrion revealed plans to seek further growth and an improvement in profit margins by setting up its own direct global sales, marketing and distribution system for new products, and for its already commercialized lines if it is unable to find ‘win-win’ strategies with existing partners. (Also see "Celltrion Eyes Direct Global Sales To Bolster Margins, Growth " - Scrip, 7 Jan, 2019.)
Celltrion Healthcare, which conducts worldwide marketing, sales, and distribution activities for biosimilar and biological medicines developed by Celltrion, had already set up branches in about 20 countries, including in the US, Europe, Japan, Singapore and Australia. But Celltrion's wider plans make it the first South Korean pharma company to set up a direct sales and distribution network overseas.
Patents Will Protect Subcutaneous Remsima
As part of its strategy on subcutaneous Remsima, Celltrion has applied for patent protection for the product “in approximately 130 countries throughout the US, Europe and Asia.”
The company believes the biologic can compete not only with branded Remicade and other biosimilar infliximabs, but also with the Humira (adalimumab) brand. Once patents are granted for subcutaneous Remsima, Celltrion expects it to be protected until 2037.
A survey of physicians conducted during United European Gastroenterology Week 2018 revealed that they preferred infliximab as the first-line treatment for inflammatory bowel disease, but administered subcutaneous adalimumab to some patients because of convenience. They viewed the infliximab intravenous and subcutaneous package as a good treatment option as patients can start their treatment with the intravenous version and once they are stabilized can be switched to the subcutaneous formulation.
The firm has previously observed that “as physicians prefer usage of IV and SC versions of the same substance, we believe we can dominate this market.” (Also see "Celltrion Eyes Direct Global Sales To Bolster Margins, Growth " - Scrip, 7 Jan, 2019.)
However, Emerton pointed out, commercializing subcutaneous Remsima would require a different approach in terms of marketing to previous Celltrion biosimilars.
“Celltrion will now have to detail this product at the physician level,” he suggested. “Unlike biosimilars, where there has been a push to switch from the brand to the biosimilar,” he explained, “there is no original subcutaneous version from which to switch. So that will be difficult.”
To support anticipated strong global demand for Remsima, especially in the EU and US, the Korean company recently enlisted Lonza to manufacture the drug substance at its biologics facility in Singapore. (Also see "Celltrion Enlists Lonza To Help Make Its Remsima" - Generics Bulletin, 5 Sep, 2019.)
A version of this article was first published in Scrip's sister publication Generics Bulletin.