Biosimilar Disease-Modifying Antirheumatic Drugs
At least 37 biosimilars for 5 biologic disease-modifying antirheumatic drugs (DMARD)9 were in development as of July 2015. The FDA appears poised to approve a second biosimilar for the US market, which would be the first US biosimilar DMARD. In February 2016, ADAC members voted 21 to 3 to recommend the FDA find Celltrion’s CT-P13 highly similar to Janssen Biotech’s Remicade (infliximab), which is an anti-tumor necrosis factor (anti-TNF) monoclonal antibody.19
The randomized, phase 3, multicenter PLANETRA trial compared the safety and efficacy of CT-P13 with Remicade in 606 adults with active RA.20 After 30 weeks of treatment, 61% of patients in the CT-P13 arm vs 59% of patients in the Remicade arm had achieved an ACR20 response, which was the primary efficacy end point. Rates of good to moderate response and remission were also similar in both arms. Data showed no significant difference between treatment arms in the rate of adverse events or the percentage of patients with detectable antidrug antibodies. Overall, the findings showed the biosimilar and reference product had equivalent efficacy and safety, as well as similar immunogenicity and pharmacokinetic profiles.20
The phase 1 randomized PLANETAS study compared CT-P13 with Remicade in 250 patients with ankylosing spondylitis and found the 2 drugs had similar pharmacokinetic profiles and immunogenicity at multiple time points throughout the study.21 Safety and efficacy profiles were also similar between the drugs.
The BLA for CT-P13 seeks approval for the same indications as Remicade: Crohn disease (adult and pediatric), ulcerative colitis (adult and pediatric), rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Ongoing studies are evaluating CT-P13 in patients with Crohn disease and ulcerative colitis. Dr Kay noted that “CT-P13 was approved by the EMA and by regulatory authorities in South Korea, Colombia, Turkey, Australia, and India for all indications for which Remicade is approved.”
Although data were not presented for every indication requested, the majority of ADAC members agreed that the data supported approving CT-P13 for all indications except pediatric ulcerative colitis (the Remicade patent is in force until September 2018) based on its biosimilarity to Remicade. Celltrion did not seek approval to have CT-P13 designated as interchangeable with Remicade. However, the FDA has discretion to decide whether existing data support an interchangeable designation, and some have speculated the agency may exercise this option with CT-P13 because the FDA included data on switching in its briefing materials for the ADAC meeting.22
The FDA is considering 2 other BLAs for DMARD biosimilars. Sandoz filed a BLA in October 2015 for a proposed unnamed biosimilar for Enbrel (etanercept), and Amgen filed a BLA in January 2016 for ABP 501, a biosimilar candidate for Humira (adalimumab). In January 2016, the EMA approved a different etanercept biosimilar from Samsung BioLogics, which was originally called SB4 but is being marketed as Benepali. Data from a randomized, phase 3 study that compared Benepali with Enbrel in approximately 600 patients with RA showed the drugs had equivalent efficacy at 24 weeks. Adverse effect rates were similar between the treatment arms, but Benepali was associated with less immunogenicity than the reference drug (.7% vs 13%, respectively).23