Rituximab Biosimilar Is Safe, Effective, and Cost-Saving in RA, but When Will US Patients Benefit?

When Celltrion and Teva’s biosimilar rituximab, CT-P10, earned FDA approval under the brand name Truxima in late 2018, it was authorized only for oncology indications, as the drug’s sponsors did not seek indications in inflammatory diseases because of issues related to patent exclusivity on some indications. However, the biosimilar has shown efficacy in treating rheumatoid arthritis (RA), and a European analysis found that the budget impact of introducing CT-P10 could dramatically reduce the cost to treat severe RA.

In a phase 3 study of CT-P10,¹ 372 patients with RA were assigned to receive CT-P10 (n = 161) or either EU-licensed or US-licensed reference rituximab at weeks 0 and 2. The primary efficacy end point was the least squares mean change from baseline in a disease activity score in a count of 28 joints using C-reactive protein (DAS28-CRP) at week 24.

Median B cell counts decreased to below the lower limit of quantification immediately after the first infusion and remained below this level up to week 24 in both groups. At week 24, the least squares mean (SD) change in DAS28-CRP was −2.13 (0.175) for the CT-P10 group and −2.09 (0.176) for the reference group. The 95% CI (−0.29 to 0.21) fell within the predefined statistical equivalence margin of ±0.5.

Mean decreases from baseline in DAS28-CRP were similar in both groups, as was improvement in DAS28 as measured with erythrocyte sedimentation rate (DAS28-ESR). At week 24, the proportions of patients achieving European League Against Rheumatism (EULAR) criteria for a good or moderate response or American College of Rheumatology criteria for clinical response were similar between groups.

The proportion of patients with antidrug antibodies (ADA) in both groups at baseline was 11.8% in the biosimilar group and 9.5% in the reference group. At week 24, the proportions of patients with ADAs detected were 14.9% and 23.2% in each group, respectively. One patient in each group tested positive for neutralizing ADAs.

In total, 59.6% of patients in the biosimilar arm had an adverse event (AE) versus 51.7% of patients in the reference arm. Most AEs were grade 1 or grade 2, with the most frequently reported AEs being infusion-related reactions and upper respiratory tract infections.

In an open-label extension,² patients who completed up to 72 weeks of the phase 3 study were eligible to receive up to 2 doses of CT-P10. In total, 38 patients from the biosimilar group and 20 patients from the reference group received CT-P10 in the extension study. At 24 weeks after the first course of treatment in the extension, the investigators found no statistically significant differences between the maintenance (CT-P10-only) group and the switch (reference to CT-P10) group in DAS28-ESR or DAS28-CRP. The proportions of patients in the maintenance and switch groups achieving a good or moderate EULAR response were also comparable. AEs were reported in 23.7% of the maintenance group and 20.0% of the switch group. ADAs were detected in 13.2% of patients in the maintenance group and in 15.0% of patients in the switch group.

These findings, which demonstrate that CT-P10 is effective in treating RA and that patients can be switched to CT-P10 without an impact on safety or efficacy, suggest that the less expensive CT-P10 can be used in treating patients with RA as a means to reduce the cost burden associated with the brand-name Rituxan.

One recent budget impact analysis³ underscored the savings that health systems can expect to reap from using biosimilar rituximab. The analysis focused on the 5-year impact of CT-P10 (or rival rituximab biosimilar GP2013, Rixathon) in the Italian healthcare system. According to the paper’s authors, from the hospital perspective, the cost to treat patients with severe RA using the reference product is €10,166,057 (approximately $11,585,747). If all patients were to be treated with a biosimilar by 5 years after biosimilars became available, the cost to treat them would drop to €4,986,033 (approximately $5,682,333).

When the United States could benefit from such biosimilar savings for patients with RA remains to be seen, however, as it is not known; the FDA has not yet clarified how indications for biosimilars can be “carved-in” after a drug’s approval, and GP2013, which could rival Truxima, will no longer be considered for the US market according to its sponsor, Sandoz.

References

1. Park W, Bozic-Majstorovic L, Milakovic D, et al. Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled phase 3 trial. MAbs. 2018;10(6): 934-943. doi: 10.1080/19420862.2018.1487912.

2. Park W, Suh CH, Shim SC, et al. Efficacy and safety of switching from innovator rituximab to biosimilar CT-P10 compared with continuous treatment with CT-P10: results of a 56-week open-label study in patients with rheumatoid arthritis. BioDrugs. 2017;31(4): 369-377. doi: 10.1007/s40259-017-0233-6.

3. Rognoni C, Bertolani A, Jommi C. Budget impact analysis of rituximab biosimilar in Italy from the hospital and payer perspectives [published online June 29, 2018]. GRHTA. doi: 10.1177/2284240318784289.