Noticia de Contratación

While the FDA approved Celltrion and Teva’s biosimilar rituximab, CT-P10 (Truxima), for oncology indications only after its sponsors did not pursue indications for nonmalignant diseases due to intellectual property issues, the biosimilar has been studied extensively in rheumatoid arthritis (RA) and is approved for use in RA in the European Union.

Recently, researchers reported 72-week results from a phase 3 trial of the biosimilar in patients with RA, in which they concluded that the product was well tolerated in long-term use and that switching from the reference did not yield differences in safety, efficacy, pharmacodynamics (PD), or immunogenicity.

Previous results from the phase 3 study have been reported elsewhere up to week 24, and the new data present results from an extension period, from week 48 to week 72, after a main treatment period in which patients had received up to 2 treatment courses of the biosimilar or its EU- or US-licensed reference.

In the extension, the 122 patients who had received the biosimilar in the main treatment period continued to receive the biosimilar, and the 47 patients who had received the EU reference switched to the biosimilar. A total of 64 patients who received the US reference in the main period stayed on the same treatment, while 62 who had received the US reference switched to the biosimilar.

At week 72, the mean (SD) change disease activity score in a count of 28 joints (DAS28) with C-reactive protein (CRP) was similar among groups:

• Biosimilar only, −3.0 (1.20)
• US reference only, −3.0 (1.32)
• US reference to biosimilar, −2.9 (1.27)
• EU reference to biosimilar, −3.0 (1.11)

Improvement measured by DAS28 with erythrocyte sedimentation rate; the proportion of patients achieving the American College of Rheumatology (ACR)’s criteria for 20%, 50%, and 70% improvement; and the proportion of patients achieving a good or moderate European League Against Rheumatism (EULAR) with CRP response were similar among groups. The proportions of patients achieving remission by ACR and EULAR criteria were also comparable among groups.

B-cell levels were comparable among groups, and there were no discernable differences in median B-cell counts among those who switched and those who did not switch treatments.

Most patients did not develop antidrug antibodies (ADAs) during the main period or the extension. Of the 18 patients who had ADAs during the extension, 16 had ADAs up to the baseline of the extension. The 2 patients who developed new ADAs, 1 in the US reference only group and 1 in the US reference to biosimilar group, did not have neutralizing antibodies; both went on to achieve remission or low disease activity.

The most commonly reported adverse events (AEs) among all groups were upper respiratory tract infections, urinary tract infections, and infusion-related reactions. Most infection AEs were grade 1 or 2 in severity. Five serious AEs were reported in 5 patients, and 1 of these (pneumonia) was considered to be related to rituximab.

These extension period data, say the researchers, show that switching from the US or EU reference rituximab to the biosimilar had no adverse impact on the efficacy, PD, immunogenicity, or safety of rituximab treatment for patients with RA, and that the biosimilar is effective and well tolerated up to week 72.