Rituximab biosimilars comparable to originator for advanced follicular lymphoma
Two upcoming rituximab biosimilars GP2013 and CT-P10 were shown to be comparable to the originator rituximab with regards to safety and efficacy in managing previously untreated advanced follicular lymphoma, according to two multinational, double-blind, phase III trials.
“Wider availability of biosimilars is … eagerly awaited and they are being counted on in what is sometimes referred to as a biosimilar revolution to lower drug prices and widen access to effective medicines,” wrote the editorialists from the Lancet Haematology. [Lancet Haematol 2017;4:e341]
Comparable overall response with GP2013
The ongoing ASSIST-FL* study randomized 629 patients (aged ≥18 years) with previously untreated, Ann Arbor stage III/IV follicular lymphoma of histologic grades 1, 2, or 3a to receive GP2013 or rituximab, both in combination with cyclophosphamide, vincristine, and prednisone (CVP) for eight cycles during the combination phase. This was followed by the maintenance phase whereby responders continued on monotherapy for another 2 years. [Lancet Haematol 2017;4:e350-361]
After a median follow-up of 11.6 months, the study met its primary endpoint of comparability in overall response between GP2013 and rituximab ─ with similar proportion of patients in both arms achieving an overall response, defined as a complete or partial response in the combination phase (87 percent vs 88 percent, difference of -0.40 percent which falls within the equivalence margin).
Similar rates of adverse events (AEs; 93 percent vs 91 percent) and serious adverse events (23 percent vs 21 percent) were observed in the GP2013 and the rituximab arms, with neutropenia being the most common AE (26 percent vs 30 percent in the combination phase and 10 percent vs 6 percent in the maintenance phase). Also, comparable proportion of patients in both arms developed antidrug antibodies (2 percent vs 1 percent).
CT-P10 noninferior to rituximab
The ongoing study of CT-P10 randomized 140 patients with similarly advanced disease as ASSIST-FL in a 1:1 ratio to intravenous CT-P10 375 mg/m2 or rituximab, in addition to CVP, on day 1 of a 21-day cycle for eight times. [Lancet Haematol 2017;4:e362-373]
The proportion of patients who achieved an overall response was similar in both the CT-P10 and the rituximab arms (97 percent vs 93 percent), corresponding to a 4.3 percent difference which according to the authors, was within the predefined noninferiority margin.
CT-P10 also demonstrated equivalent pharmacokinetics to rituximab, with an AUCτ** of 102.25 percent and CmaxSS*** of 100.67 percent for the CT-P10/rituximab ratio, with both the confidence intervals within the prespecified margin of bioequivalence.
Treatment-emergent AEs occurred at similar rates in both groups (83 percent vs 80 percent). As with ASSIST-FL, neutropenia was also the most common grade 3/4 treatment-emergent AE in each group in this study (21 percent vs 10 percent).
Caveats despite optimistic outlook
“Although the outlook is optimistic, we think that caution is needed in this arena,” according to the editorialists.
One main concern is whether biosimilars will actually help reduce costs substantially, given that biologicals entail complicated manufacturing and a more costly process of gathering evidence for licensing than those needed for generic drugs, they wrote.
Another concern is whether the biosimilars are as safe and interchangeable with the reference product.
“Strong safeguards should be in place to ensure that patients who have responded well to existing medicine and are switched for non-clinical reasons are closely monitored to ensure efficacy and safety,” cautioned the editorialists. “If patients do not maintain the efficacy with a biosimilar that they achieved with the reference product, they should have the option of reverting back to the reference drug.”
“While the idea of the biosimilars revolution is an attractive one, we must be vigilant with their use to ensure a new group of problems is not created,” they added.