As reported in Gastroenterology, Dr. Byong Duk Ye of XX and colleagues randomized 131 patients from 50 sites in 15 countries to CT-P13 SC or IV after all had received two full doses of the IV formulation (by week 6) without safety concerns.
Patients' median age was about 34; about half were men; most (94%) were White; none were Black. All were TNF-inhibitor naïve, had received no prior biologics, and failed conventional therapy.
Patients received either CT-P13 SC every two weeks from weeks 6-54 or CT-P13 IV every eight weeks from weeks 6-22.
At week 30, patients receiving CT-P13 IV switched to CT-P13 SC until W54. The primary pharmacokinetic endpoint was non-inferiority of CT-P13 SC to CT-P13 IV for the observed pre-dose CT-P13 concentration at week 22.
The primary endpoint of non-inferiority was met with a geometric least squares means (gLSM) ratio for Ctrough at week 22 of 1,154.17%. Clinical remission rates were comparable between the groups at weeks 30 and 54. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between groups, including after switching.
Dr. Ioannis Economou, Director, Gastroenterology Clinical Trials Program at Rush University Medical Center in Chicago, commented by email to Reuters Health that although the formulation has been approved in Europe, "The FDA required submission for CT-P13 SC as a new drug, since the dose and type of administration is different than the IV drug formulation. Two studies for CD and UC are under way, with expected completion by 2022 and FDA approval the same year."
"I am expecting future studies assessing whether the relatively low variation in drug levels of the SC formulation would be beneficial compared to the high peak and low trough serum concentrations achieved with the intravenous formulation," he said. "Off-label dose escalation of the IV formulation has been applied and might be required for the subcutaneous formulation too."
"The SC formulation might provide a strong alternative for disease maintenance of patients who have been hospitalized with acute severe IBD who require IV induction therapy," he suggested. "Elimination of the IV administration cost might provide a significant cost benefit for the insurance and the patient."
Dr. Arun Swaminath, Chief, Division of Gastroenterology and Director, IBD program at Lenox Hill Hospital in New York City, told Reuters Health by email, "Definitely looking forward to having another option for my patients. I see this as 'catching up' with what's already available for patients in Europe."
"The study's primary endpoint was pharmacokinetic...but there were some surprising findings," he noted. "The SC arm actually had higher trough level concentrations; however, the IV and SQ arms has similar efficacy at the end of the study, suggesting that the higher peaks achieved with IV dosing (and lower valleys) may be as important as keeping the drug level above a certain minimum concentration between dosing, and this may cause us to modify our current thinking about dosing strategy."
"Interestingly," he said, "there were similar levels of antibodies that seemed to be blocking the effect of CT-P13 in both groups - a bit unexpected, given that the advantage did not go to the SC group with more steady levels between doses."
"Finally," he added, "the clinical benefits appeared excellent, but this was a biological-naïve population and I would expect more challenges among the biologically exposed population."
Dr. Moheb Boktor, Assistant Professor, Division of Digestive and Liver Diseases at the University of Texas Southwestern Medical Center in Houston, also commented by email. "Most of our patients are young, with busy schedules. They would rather receive an SC injection in less than a minute than four hours of infusion. This would improve compliance, decrease cost and minimize side effects."
"Clinicians should monitor drug levels and local reactions related to SC injection and confirm patients are appropriately administering the drug," he added.
The study was funded by Celltrion, Inc (Incheon, Republic of Korea). Corresponding authors Dr. Byong Duk Ye of the University of Ulsan College of Medicine, who received a research grant from the company, and Dr. Walter Reinisch of the Medical University of Vienna, who has received fees from the company, did not respond to requests for a comment. Many of the other coauthors received fees from the company.
SOURCE: https://bit.ly/3lShOws Gastroenterology, online March 5, 2021.
By Marilynn Larkin
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