Tony Hagen is senior managing editor for The Center for Biosimilars®.
Based on clinical studies on dosing, efficacy, and pharmacokinetics, European authorities have recommended Celltrion's subcutaneous infliximab biosimilar (Remsima SC) for 5 new indications.
Celltrion Healthcare’s subcutaneous infliximab biosimilar (Remsima SC) has been recommended for approval for 5 new indications by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).
Already indicated for rheumatoid arthritis in Europe (November 2019), Remsima SC has been recommended for marketing authorization for ankylosing spondylitis, Crohn disease, ulcerative colitis (UC), psoriatic arthritis, and psoriasis. The infliximab biosimilar is marketed as Inflectra in the United States.
Studies Support Recommendations
Celltrion, based in Incheon, Republic of Korea, said the CHMP recommendations were supported by phase 1/3 studies that compared the pharmacokinetics, efficacy, and safety of the intravenous and SC formulations of Remsima in patients with Crohn disease and UC. CHMP has recommended a 120 mg dose of Remsima SC for the existing and additional 5 recommendations in adults regardless of body weight, based on the results.
Walter Reinisch, director of the Clinical IBD Study Group at Medical University of Vienna, Austria, said the SC formulation offers patients treatment flexibility during maintenance treatment with infliximab and “takes significantly less time than the current intravenous formulation, thereby reducing the time patients need to be in medical settings with infusion administrations.”
That observation takes on added significance against the backdrop of the coronavirus disease 2019 pandemic, he added, because patients “must take extra precautions and visit hospitals only when absolutely necessary.” The SC formulation can be administered by patients without assistance from health care professionals.
The clinical studies that supported the CHMP recommendation involved randomization of patients to varied doses of the SC formulation or continued intravenous (IV) administration.
Following loading doses of IV 5 mg/kg received at weeks 0 and 2, patients were randomised at week 6 to receive either SC 120 mg (<80 kg) or 240 mg (≥80 kg) every 2 weeks in the SC arm, or they were continued on IV 5 mg/kg every 8 weeks in the IV arm. Starting from week 30, patients in the IV 5 mg/kg cohort were switched to SC 120 mg or 240 mg, according to body weight, Celltrion said in a statement.
The Crohn Disease Activity Index and partial Mayo scores for UC disease activity decreased over time in both arms until week 30. Comparable improvement was seen in the remaining IV patients switched to SC formulation starting at week 30 of the trial. Celltrion said rates of clinical response and remission at week 54 were maintained, and mucosal healing in Crohn disease and UC continued to improve. Serum concentrations were comparable and consistent up to week 54, and the overall safety profile was comparable between SC and IV arms.
Remsima has been on the market for 5 years and now is available in over 90 countries, the company said. “If approved by the EMA, Remsima will be the first infliximab to have both intravenous and subcutaneous formulations to treat patients with ankylosing spondylitis, Crohn disease, ulcerative colitis, psoriatic arthritis and psoriasis,” Hyoung-Ki Kim, vice chairman, said in the statement.
Through regulatory filings, Celltrion hopes to obtain patent protection for the SC formulation and dosage through 2037 and 2038, respectively, in the United States, Europe, and Asia.
Earlier this month, Celltrion announced that its infliximab product will be tested in the CATALYST trial for its potential in controling cytokine release syndrome, which occurs in patients with COVID-19.
Late last year, Celltrion reported that as of the third quarter of 2018 its infliximab biosimilar had achieved a 56% share of the European market for infliximab.