During the United European Gastroenterology Week 2019 meeting, held in Barcelona, Spain, researchers presented results of a phase 1 pivotal study of a subcutaneously administered formulation of biosimilar infliximab, CT-P13 (Remsima, Inflectra), in patients with inflammatory bowel disease (IBD).
In September, Republic of Korea-based biosimilar developer Celltrion received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use for its subcutaneous formulation of biosimilar infliximab, CT-P13 (Remsima, Inflectra), for the treatment of rheumatoid arthritis, and final authorization from the European Commission is expected in the coming weeks.
The biosimilar developer has also been investigating the novel formulation of the product in inflammatory bowel disease (IBD), and this week, during the United European Gastroenterology Week 2019 meeting, held in Barcelona, Spain, researchers presented results of a phase 1 pivotal study of the product in patients with IBD.
The findings, presented in a late-breaking abstract session, show that the subcutaneously administered biosimilar was noninferior to the intravenously administered version at week 22, and had comparable safety and efficacy up to week 30.
In the study, 136 patients with either Crohn disease (CD) or ulcerative colitis (UC) were given loading doses of intravenous CT-P13, at a dose of 5 mg per kg, at weeks 0 and 2. Then, they were randomized at week 6 to either receive a subcutaneous dose of 120 mg or 240 mg every 2 weeks, or to receive intravenous therapy at 5 mg per kg every 8 weeks. The primary endpoint was trough concentration at week 22. Noninferiority was prespecified as the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of the geometric least squares mean being higher than 80%.
The lower bound of the 90% CI was greater than 80% at week 22, with higher geometric LS mean of trough concentration in the subcutaneous administration arm, and the researchers note that “Frequent administration of small doses and delayed absorption of [subcutaneous CT-P13] led to more constant exposure compared to [intravenous] dosing."
With respect to efficacy up to week 30, clinical response and remission were both induced and maintained and were comparable in both treatment arms. The combined clinical remission rates for patients with CD and UC at week 30 were comparable between the subcutaneous and intravenous arms, respectively (66.7% vs 54.7%; P = .1620).
Injection site reactions (ISRs) occurred more commonly in the subcutaneous arm, but all ISRs were grade 1 or 2 in intensity, and the safety profiles of the 2 CT-P13 products were generally similar. The incidence of antidrug antibodies was slightly lower in subcutaneous group at week 30 than in the intravenous group (37.9% vs 3.8%).
“CT-P13 [subcutaneous] infliximab has the potential to become the most innovative biosimilar treatment—improving convenience and allowing patients to have more control of their treatment in addition to direct clinical benefits,” said Stefan Schreiber, MD, PhD, director of the Clinic for Internal Medicine at Kiel Campus of the University Hospital Schleswig-Holstein in Germany, and first author of the study. “Not without reason the [intravenous/subcutaneous] sequence therapy that has been implemented into most development paths for novel molecules.”
In a statement, Celltrion noted that it plans to file for European regulatory approval for the subcutaneous formulation in IBD during the second half of 2020.
Schreiber S, Leszczyszyn J, Dudkowiak R, et al. Noninferiority of novel subcutaneous infliximab (CT-P13) to intravenous infliximab (CT-P13) in patients with active Crohn’s disease and ulcerative colitis: week 30 results form a multicenter, randomized controlled pivotal trial. Presented at: United European Gastroenterology Week 2019; October 29-23, 2019; Barcelona, Spain.