South Korea-based firm Celltrion has made waves at the American College of Rheumatology 2013 conference by presenting data from a clinical trial that found no change in safety or efficacy when patients with rheumatoid arthritis were switched from treatment with Remicade (infliximab) to Celltrion's biosimilar, Remsima. Separately, the firm announced it will resume Phase III development of its biosimilar of Rituxan/MabThera (rituximab). * Please note that this article was amended on 7 November to provide additional clarity.
IHS Global Insight perspective | |
Significance | Celltrion has released data from a two-year crossover study held in the United States showing that patients with rheumatoid arthritis or ankylosing spondylitis switched from treatment with Remicade (inflixmab) to biosimilar Remsima showed no statistically significant changes in efficacy or side effects. |
Implications | Separately, the South Korean firm announced it is set to continue Phase III development of its biosimilar of Rituxan/MabThera (rituximab), after releasing results from a successful Phase I trial. |
Outlook | Remicade is under patent protection until 2018 in the United States, but Celltrion will gain one-year exclusivity upon launch in that country if the US FDA agrees that the data proves interchangeability. The South Korean firm expects the data to assist in marketing Remsima to countries and hospitals that acquire only one active pharmaceutical ingredient during drug tenders. |
South Korea-based Celltrion has made waves at the American College of Rheumatology 2013 conference by presenting data from a study that demonstrated no change in terms of safety and efficacy when rheumatoid arthritis patients were switched from treatment with Johnson & Johnson (J&J)/Merck & Co (US)'s Remicade (infliximab) to Celltrion's biosimilar version, Remsima.
Remsima shows potential clinical and quality-of-life interchangeability
The crossover study held in San Diego, United States, was an open-label one-year extension of the earlier two-year PLANTERA study that was used for the filing of CT-P13, which in August became the world's first mAb biosimilar to gain marketing approval in developed markets (see Europe: 11 September 2013: Europe approves Celltrion/Hospira's Remicade biosimilar). The cross-over study examined two groups of patients who had already been treated for one year with either Remsima or Remicade. Out of 606 patients in total, 304 patients were swapped from treatment with Remicade to treatment with the biosimilar, while the remainder continued to be treated with Remsima. The study found no significant difference between the two groups in terms of efficacy and safety. Celltrion also carried out a health assessment questionnaire of patients within the study that found the biosimilar approved comparable improvement in quality of life. For a link to the firm's press release, see here.
Rituxan biosimilar development resumed
Separately, the firm is also set to initiate a global Phase III trial for CT-P10, its biosimilar of Biogen Idec (US)/Roche (Switzerland)'s rheumatoid arthritis and haematological cancer drug Rituxan/MabThera (rituximab). The announcement followed successful completion of a Phase I trial in 150 patients not previously responsive to tumour necrosis factor (TNF)-alpha inhibitors, which showed CT-P10 to be equivalent to the original drug in terms of pharmacokinetics, efficacy, and safety. No specific timelines were given in terms of how long the Phase III development is expected to continue.
The news confirms a Celltrion announcement earlier this year that it would delay Phase III development of CT-P10 until completion of the Phase I trial, on the advice of several national regulators (see United States - Switzerland - South Korea: 22 April 2013: Celltrion delays development of rituximab biosimilar).
Outlook and implications
Celltrion has taken a risk in holding a trial to demonstrate interchangeability of Remsima with Remicade – if the trial had failed the claims of similarity with Remicade would have been undermined. Now, however, the firm's future ability to market the drug will be strengthened. The South Korean firm notes that the data showing similar efficacy and safety with the originator following switching will enable Celltrion to market the product to countries or hospitals that use a tender process where only one active pharmaceutical ingredient drug can be acquired.
J&J earned USD6.1 billion in revenues from Remicade during 2012, and the firm will be concerned over the potential for more rapid erosion of these sales once patent expires. Celltrion's biosimilar version is being co-marketed with Hospira (US) and Egis (Hungary) in Europe, where launch in major markets such as the United Kingdom, France, and Germany is delayed until February 2015 due to a paediatric extension to the drug's patent. In the US – where Hospira will also co-market – Remicade's patent term runs until 2018, although Celltrion last month announced that the US FDA had approved a Europe-based trial as the basis for a future filing of the product in the US (see United States - South Korea: 18 October 2013: Celltrion approved for Remsima bridging study in preparation for US filing in 2014).
Global regulators have been wary of permitting switching between a biologic drug and a drug that is only "similar", with Mexico and Brazil among the few to currently permit switching under certain circumstances. The US FDA indicated in its February 2012 draft biosimilars guidance that switching would be permitted where an individual product has proved the risk of "alternating or switching between the use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch" (source: Quality and Scientific Considerations in Demonstrating Biosimilarity to a Reference Protein Product; see here). Under the terms of the Biologics Price Competition and Innovation Act, part of the 2010 Affordable Care Act, proving interchangeability means that Celltrion also stands to benefit from one-year exclusivity in addition to the benefits of substitution. Earlier this year, the state of Virginia became the first US state to allow substitution of a biosimilar for an originator biological product according to the FDA's guidelines (see United States: 26 March 2013: Virginia becomes first US state to allow biosimilars substitution).
The initiation of a Phase III trial of CT-P10 (rituximab) means that Celltrion is among the leaders in the development race for that molecule, a potential USD7-billion market. A number of competitors have ceased or suspended development of rituximab biosimilars, including fellow South Korean firm Samsung Biologics and Teva (Israel), citing regulatory concerns (see South Korea: 19 October 2012: Samsung Biologics cancels trial of rituximab biosimilar for regulatory reasons).