Phase I study shows equivalence of biosimilar rituximab and MabThera Posted 13/12/2013

The results of a randomized, controlled, multicentre, two-arm, parallel-group, double-blind study of CT-P10 (rituximab) in patients with rheumatoid arthritis has shown the equivalence, with respect to pharmacokinetics, efficacy and safety, of the biosimilar (CT-P10) and its reference product, Roche’s rheumatoid arthritis blockbuster MabThera/Rituxan (rituximab).

CT-P10 is a candidate biosimilar of Roche’s MabThera/Rituxan (rituximab), which is used not only in the treatment of rheumatoid arthritis, but also leukaemia and non-Hodgkin’s lymphoma, a group of cancers arising from lymphocytes or white blood cells.

South Korean biotechnology company Celltrion presented the results of the studies at the 2013 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting in San Diego, USA, which was held on 26–30 October 2013 [1].

The phase I trial of the monoclonal antibody biosimilar was carried out in 154 patients with active rheumatoid arthritis who did not respond to TNF-α inhibitors over 24 weeks. Participants were randomized 2:1 to receive two 1,000 mg intravenous infusions of either CT-P10 (n = 103) or MabThera (n = 51) with a two-week interval between infusions, co-administered with weekly methotrexate and folic acid.

The ratios (%) of the geometric means of the area under the serum concentration-time curve from time ‘0’ to time of last quantifiable concentration (AUC0–last) and maximum serum concentration (Cmax) between the CT-P10 and MabThera groups were 98.3% (90% CI: 89.6, 107.8) and 97.6% (90% CI: 92.0, 103.5), respectively. These results fell within the predefined equivalence limits of 80–125%.

The geometric mean AUCs for B-cell counts, a comparative pharmacodynamic parameter, was 20.8 cells/µL for the CT-P10 group and 20.4 cells/µL for the MabThera group. The ratio (%) of the geometric means of the AUC for B-cell count was 102% (90% CI: 98, 106).

ACR20/50/70 response rates at week 24 were 63.0%/37.0%/16.0% in the CT-P10 group and 66.7%/31.3%/14.6% in the MabThera group. The proportion of patients who had a moderate or good response at week 24 were 76.8% and 79.1% for European League Against Rheumatism (EULAR)-ESR response and 82.1% and 83.7% for EULAR-CRP response in the CT-P10 and MabThera groups, respectively.

The proportion of patients who developed anti-drug antibodies during the study was similar in both treatment groups at week 24 [CT-P10: 17.6% (18/102) and MabThera: 17.6% (9/51)]. The safety profile for CT-P10 and MabThera were also comparable at week 24; serious adverse events were reported in 16.7% of CT-P10 and 17.6% of MabThera patients.

Celltrion therefore concluded that CT-P10 and MabThera were equivalent in terms of AUC0–last and Cmax in patients with active rheumatoid arthritis. Clinical efficacy for ACR20/50/70 and EULAR response rates and pharmacodynamics for B-cell kinetics were comparable between the two treatment groups. CT-P10 was well tolerated with a safety profile comparable to that of RTX up to week 24.

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Reference

1.  Yoo DH. A Randomized, Controlled, Multicenter, 2‑Arm, Parallel‑Group, Double-Blind Study To Demonstrate The Equivalence Of CT-P10 To Innovator Rituximab With Respect To Pharmacokinetic Profile In Patients With Rheumatoid Arthritis. American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting, San Diego, US, 26–30 October 2013. Abstract:#1736.

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Source: ACR, Celltrion

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