Iranian Biosimilar Rituximab Noninferior to Its Reference in Treating CLL

A recently published study between the biosimilar and the reference rituximab, MabThera, demonstrated that the biosimilar was noninferior to the reference in terms of both efficacy and safety in treating chronic lymphocytic leukemia (CLL). 
The Center for Biosimilars Staff
September 24, 2018
Zytux was first launched in Iran in 2014, by Aryogen Biopharma, as the nation’s first biosimilar rituximab. While the Iranian health authority generally follows World Health Organization guidelines for approving biosimilars, it does not insist on comprehensive clinical trials for biosimilar approvals. Thus, data generated after approval are important for the surveillance of biosimilars in this marketplace.A recently published study comparing the biosimilar and the reference rituximab, MabThera, demonstrated that the biosimilar was noninferior to the reference in terms of both efficacy and safety in treating chronic lymphocytic leukemia (CLL).2 

The trial randomized patients 70 with previously untreated or recurrent CLL into 2 treatment arms, 1 of which received the biosimilar rituximab (n = 35) and the other of which received the reference rituximab (n = 35) together with fludarabine and cyclophosphamide in standard 28-day cycles of chemotherapy. 

Read more about rituximab in treating CLL.

Five patients in the biosimilar arm and 2 patients in the reference arm discontinued treatment, 2 patients in the reference arm died, and 3 patients in the biosimilar arm and 2 in the reference arm were lost to follow-up. 

The overall response rate (ORR)—the study’s primary endpoint—was comparable between the 2 groups, at 88% in the biosimilar arm and 89% in the reference arm, respectively. The study’s prespecified margin for noninferiority was a 20% difference in ORR; thus, noninferiortiy was demonstrated.

In both groups, peripheral blood lymphocyte counts dropped significantly from baseline and remained comparable between arms at each cycle of treatment. 

The incidence of infusion-related reactions in the first treatment cycle was slightly higher for the biosimilar group (36%) than for the reference group (20%), though the difference did not achieve statistical significance, nor did the trend persist in further cycles. 

The incidence of grade 1 thrombocytopenia was slightly higher for the reference arm than for the biosimilar arm, but grade 3 and 4 thrombocytopenia occurred more frequently in the biosimilar group. A total of 79 events of any-grade anemia occurred, and were equally distributed between both groups. Thirty-three and 36 cases of neutropenia were observed in the biosimilar and reference arms, respectively, and there was no significant difference in the rates of grade 3 or grade 4 neutropenia between groups. 

The study’s authors concluded that the biosimilar rituximab is noninferior to the reference, and that its use is associated with comparable outcomes in terms of both safety and efficacy. 

1. Krishan A, Mody R, Malhotra H. Global regulatory landscape of biosimilars: emerging and established market perspectives. Biosimilars. 2015;5: 19-32. doi: 10.2147/BS.S44052.

2. Toogeh G, Faranoush M, Razavi SM, et al. A double-blind, randomized comparision study between Zytux vs MabThera in the treatment of CLL with FCR regimen: non-inferiority clinical trial. Int J Hematol Oncol Stem Cell Res. 2018;12(2): 84-91. PMID: 30233768. 


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