First of its kind study shows that CT-P13 is comparable in efficacy, safety and tolerability to reference infliximab in patients with active Crohn’s disease, validating extrapolated approval data in this indication
March 29, 2019 07:46 AM Eastern Daylight Time
LONDON--(BUSINESS WIRE )--Celltrion Healthcare announced today that The Lancet has published the full data-set from its randomised controlled trial (RCT) of CT-P13 (biosimilar infliximab) in Crohn’s disease (CD), the PLANETCD Study. Results from the phase III study demonstrated the non-inferiority of CT-P13 to reference infliximab in biologic-naïve patients with moderate-to-severe CD.1
CT-P13 is already approved for the treatment of eight autoimmune diseases including CD, a form of inflammatory bowel disease (IBD), in more than 80 countries including the US, Canada, Japan and throughout Europe. This follows EMA approval in 2013 and FDA approval in 2016.
As per regulatory guidelines, approval of CT-P13 was based on proof of biosimilarity versus reference infliximab collected in clinical studies in patients with ankylosing spondylitis and rheumatoid arthritis that established equivalence of the drugs in pharmacokinetics (PK) and efficacy, as well as comparability in safety and immunogenicity.2 ,3 ,4 ,5 ,6 ,7 Approval of CT-P13 in IBD and other non-rheumatological indications was based on extrapolation, a process that allows approval of a biosimilar in a non-studied indication based on the totality of evidence.8, 9,10
These positive results from the CD RCT, build on the existing body of evidence in favour of CT-P13 and validate the extrapolation process on which the approval of CT-P13 was based on for the treatment of IBD.
“This is the first head-to-head study demonstrating the equal efficacy of an anti-TNF biosimilar in inflammatory bowel disease. The findings demonstrate that patients living with Crohn’s disease continue to experience comparable efficacy, pharmacodynamics, pharmacokinetics, safety and immunogenicity when switched to CT-P13 from reference infliximab. This robust evidence makes a compelling case for the use of biosimilars and will inform decision-making by gastroenterologists when choosing anti-TNF therapy for their patients,” said Professor Stefan Schreiber, Director of the Clinic for Internal Medicine at Kiel Campus of the University Hospital Schleswig-Holstein in Germany.
The 54-week RCT, involving 220 patients from 58 centres in 16 countries, showed comparable efficacy and safety profiles between all treatment groups (switched or continued groups) in patients with CD who had failed and/or were intolerant to non-biologic treatments.1
The study used the Crohn’s Disease Activity Index (CDAI), a measurement used to quantify the symptoms of CD patients in order to define response or remission of disease. The primary endpoint was set as the proportion of patients achieving a decrease of ≥ 70 points in CDAI from baseline to week 6. Non-inferiority of CT-P13 to reference infliximab with respect to response rates was established when the 95% confidence interval (CI) between the two drugs fell within the pre-specified margin.1
Mr Hyoung-Ki Kim, Vice Chairman at Celltrion Healthcare said: “The PLANETCD study is the first investigation of the therapeutic efficacy of an infliximab biosimilar powered to show non-inferiority to reference infliximab in inflammatory bowel disease. We at Celltrion Healthcare are proud to be the company leading the way in the biosimilar space as well as witness the growing recognition attributed to our products due to their high quality and cost effectiveness. This PLANETCD study published in The Lancet, together with the evidence from the influential NOR-SWITCH study, which was performed across multiple indications, support the equivalence between CT-P13 and reference infliximab.”
Notes to editors:
Additional quotes from physicians about the PLANETCD Study
“The study confirmed the validity of extrapolation for CT-P13 and add to the body of evidence supporting its use in patients with IBD,” said Professor Young Ho Kim, a global principal investigator of the study and professor of Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. “The non-inferior efficacy of CT-P13, measured by CDAI-70 response, was demonstrated as a primary endpoint after week 6, and comparable response rates were maintained up to week 54. Both efficacy and safety profiles were observed to be similar in all study arms including switching groups for a year.”
About inflammatory bowel disease
Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic disabling gastrointestinal disorders that impact every aspect of a patient’s life.11 They affect an estimated 5 million people globally;12 IBDs account for substantial costs to the healthcare system and society; the direct healthcare costs of IBDs are estimated to be €4.6-5.6 billion per year.13
About CT-P13 (biosimilar infliximab)
CT-P13 is developed and manufactured by Celltrion, Inc. and was the world’s first monoclonal antibody biosimilar approved by the European Commission (EC). It is indicated for the treatment of eight autoimmune diseases including rheumatoid arthritis and IBD. It was approved by the EC under the trade name Remsima® in September 2013 and launched in major EU countries in early 2015. The US FDA approved CT-P13 in April 2016 under the trade name Inflectra®. CT-P13 is approved in more than 89 countries (as of March 2019) including the US, Canada, Japan and throughout Europe.
About Celltrion Healthcare
Celltrion Healthcare is committed to delivering innovative and affordable medications to promote patients’ access to advanced therapies. Its products are manufactured at state-of-the-art mammalian cell culture facilities, designed and built to comply with the US FDA cGMP and the EU GMP guidelines. Celltrion Healthcare endeavors to offer high-quality cost-effective solutions through an extensive global network that spans more than 120 different countries. For more information please visit: http://www.celltrionhealthcare.com/ 
About The Lancet medical journal
The Lancet is the world's leading independent general medical journal. The journal's coverage is international in focus and extends to all aspects of human health. The Lancet publishes the original primary research and review articles of the highest standard. The Lancet is stringently edited and peer-reviewed to ensure the scientific merit and clinical relevance of its diverse content. Drawing on an international network of advisers and contributors, The Lancet meets the needs of physicians by adding to their clinical knowledge and alerting them to current issues affecting the practice of medicine worldwide. The Lancet has an Impact Factor of 53.254.14
1 Byong Duk Y, et al. Efficacy and safety of biosimilar CT-P13 compared with innovator infliximab in patients with active Crohn’s disease: An international, randomised, double blind, parallel-group, non-inferiority phase III study, The Lancet. Available at http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32196-2/fulltext  [Last accessed March 2019]
2 Yoo DH, et al. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when co-administered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis. 2013;72(10):1613-20.
3 Yoo DH, et al. A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study. Arthritis Res Ther. 2016;18:82.
4 Yoo DH, et al. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study. Ann Rheum Dis. 2017;76(2):355-363.
5 Park W, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis. 2013;72(10):1605-12.
6 Park W, et al. Comparable long-term efficacy, as assessed by patient-reported outcomes, safety and pharmacokinetics, of CT-P13 and reference infliximab in patients with ankylosing spondylitis: 54-week results from the randomized, parallel-group PLANETAS study. Arthritis Res Ther. 2016;18:25.
7 Park W, et al. Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study. Ann Rheum Dis. 2017;76(2):346-354.
8 Jung SK, et al. Physiochemical characterization of Remsima. MAbs 2014; 6: 1163-77.
9 United States Food and Drug Administration. CT-P13 (infliximab biosimilar) briefing document for the arthritis advisory committee. February 2016. Available from: https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/arthritisadvisorycommittee/ucm484860.pdf  [Last accessed March 2019]
10 European Medicines Agency. Assessment report: Remsima. June 2013. EMA/CHMP/589317/2013. Available from: https://www.ema.europa.eu/documents/assessment-report/remsima-epar-public-assessment-report_en.pdf  [Last accessed March 2019]
11 Molodecky NA, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012; 142(1)46–54. Available at www.gastrojournal.org/article/S0016-5085  (11)01378-3/pdf [Last accessed March 2019]
12 The European Federation of Crohn’s & Ulcerative Colitis Associations. What is IBD? Science. Available at: www.efcca.org/en/science [Last accessed March 2019]
13 Burisch J, et al. The burden of inflammatory bowel disease in Europe. Journal of Crohn's and Colitis (2013)7,322-337.
14 The Lancet, Available at: https://www.journals.elsevier.com/the-lancet  [Last accessed March 2019]