*PARIS - Two different biosimilar drugs, one a mimic of infliximab, the other modeled on etanercept, closely matched the efficacy and safety of their brand-name counterparts in a pair of separate, randomized, controlled studies.
In one study, treatment with infliximab and a biosimilar agent showed virtually identical efficacy and safety performance at several time points during the first 16 weeks of treatment of 189 patients with rheumatoid arthritis in a head-to-head, randomized comparison done at 23 centers in India.
In the second study, an agent produced to match etanercept showed very similar efficacy and safety to the branded formulation in a total of 233 randomized patients treated for 24 weeks at several centers in Korea.
The second study run in India was the "first clinical trial of a biosimilar infliximab to demonstrate and report kinetics of response to treatment at multiple time points prior to the plateau phase," which starts at about weeks 16, Dr. Jonathan Kay said at the annual European Congress of Rheumatology. It provides "convincing evidence of therapeutic equivalence," and also serves as a "new paradigm for comparative effectiveness testing of biosimilars," said Dr. Kay, a professor of medicine at the University of Massachusetts in Worcester.
Dr. Jonathan Kay
Dr. Kay and his colleagues randomized 62 patients with active rheumatoid arthritis (RA) on stable doses of methotrexate to infliximab (Remicade) and 127 patients to BOW015, the biosimilar under study. They measured the proportion of responders at 2, 6, 14, and 16 weeks, with the study’s primary endpoint the percentage of patients showing an American College of Rheumatology 20 (ACR20) response at 16 weeks. The proportion of responders at each of these four time points was virtually identical, Dr. Kay reported. At 16 weeks, the percent of ACR20 responders was 86% in the infliximab arm and 90% in the biosimilar arm. The percent of ACR50 and ACR70 responders was also virtually the same in both treatment arms at 16 weeks, and the percent of ACR20 responders was virtually identical in the two treatment arms at weeks 2, 6, and 14.
The safety profiles of the two drugs also showed no statistically significant differences for any parameter measured except for the incidence of skin disorders, which occurred in one patient treated with the biosimilar and four patients treated with infliximab, a statistically significant difference.
At the same session, Dr. Sang-Cheol Bae of the Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, presented findings from a randomized, controlled trial that compared the etanercept biosimilar HD203 with etanercept (Enbrel). Dr. Bae and his colleagues randomized 115 patients with active rheumatoid arthritis to HD203 and 118 patients to etanercept, both in combination with methotrexate, with the primary endpoint set as the proportion of patients achieving ACR20 by week 24. No statistically significant differences were seen between the patient groups for this primary endpoint, and equivalence in efficacy was demonstrated within predefined margins. The percent of ACR20 responders at 24 weeks was 79% in the biosimilar arm and 76% with etanercept.
Dr. Sang-Cheol Bae
Secondary analyses showed that the ACR50 responses occurred in 65% of the patients on the biosimilar at 24 weeks and in 53% of patients on etanercept, a statistically significant difference; and after 48 weeks of treatment, the ACR50 rate was 68% in the biosimilar arm and 55% with etanercept, also a statistically significant difference. The two study groups showed no significant difference in the rate of ACR70 responders after 24 or 48 weeks, and also no statistically significant difference in the rate of ACR20 responders after 48 weeks.
The results also showed that the biosimilar was "well tolerated," with a safety profile "comparable" with etanercept, Dr. Bae said.
Dr. Kay has received research funding and/or consulting income from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Epirus, Genentech, Hospira, Janssen, Pfizer, Roche, and UCB. Dr. Bae acknowledged receiving consulting income and/or research support from Abbott, Bristol-Myers Squibb, Eisai, GlaxoSmithKline, Hanwha Chemical, Merck Serono, MSD, and Pfizer.
* This story was updated 6/13/14.