Paris, France—Rheumatologists, patients, and payers in the United States are eager to determine whether biosimilars of expensive biologic therapies for rheumatoid arthritis (RA) and other rheumatic conditions will pass the hurdles of testing for approval by the US FDA regulatory agencies. At the recent 2014 European League Against Rheumatism (EULAR) Congress, 2 separate randomized, double-blind, phase 3 trials showed progress.
The trials found that biosimilars of etanercept and infliximab are equivalent to their reference compounds. These studies are important steps toward establishing true equivalence, but questions remain.
Although some biosimilars are approved in Canada, Europe, India, and Asia, they have not yet been approved in the United States. Expectations are high, and it is assumed that biosimilars will be much less expensive, but they still have to be shown to be cost-effective, according to Maya Buch, MD, from the University of Leeds, United Kingdom. Rheumatologists will need to have full confidence that biosimilars are equivalent to the reference compounds before they prescribe them to patients, she added. That will depend on what the studies show.
The first study compared the etanercept biosimilar HD203 versus etanercept in Korean patients with RA. The primary end point of demonstrating equivalence was met, and the safety profiles of the 2 compounds were comparable, according to presenting author Sang-Cheol Bae, MD, Hanyang University Hospital for Rheumatic Diseases in Seoul, South Korea.
“As more biosimilars become available, it is critical that patients, healthcare providers, and regulators can have confidence in the safety and efficacy of these compounds,” Dr Bae stated.
Overall, 294 patients with active RA were randomized to receive 25 mg of HD203 (n = 147) or 25 mg of etanercept (n = 147), in combination with methotrexate subcutaneously twice a week for 48 weeks. The primary end point was the proportion of patients who achieved at least a 20% response according to American College of Rheumatology 20% (ACR20) criteria for improvement by week 24. Both groups achieved similar results for the primary end point: 82.48% for HD203 compared with 81.36% for etanercept.
Results were also similar on the ACR20 at week 12 and week 48, Dr Bae continued, but HD203 achieved numerical superiority—not statistically significant—compared with etanercept for achieving at least a 50% response on ACR50 at weeks 24 and 48.
The rate of treatment-emergent adverse events was 76.87% for HD203 compared with 78.08% for etanercept. There were no unexpected adverse events and few patients developed antidrug antibodies.
In a second phase 3 trial, investigators found that BOW015, a biosimilar of infliximab, had comparable efficacy and safety to the biosimilar of infliximab. The investigators randomized 189 patients with active RA on stable doses of methotrexate to either BOW015 or infliximab. This study is distinct from other studies of biosimilars conducted thus far in that efficacy was evaluated at different time points leading up to the primary end point for ACR20 response at week 16, explained presenting author Jonathan Kay, MD, University of Massachusetts Memorial Medical Center, Worcester. The percentages of responders at weeks 0, 2, 6, and 14, leading up to the primary end point were comparable for BOW015 and infliximab.
“This provides particularly convincing evidence that these compounds are therapeutically equivalent,” according to Dr Kay.