Biosimilar matches rituximab in large follicular lymphoma trial

MADRID – The biosimilar GP2013 met the criteria for therapeutic equivalence to rituximab in a large comparator trial of previously untreated patients with aggressive follicular lymphoma.

Based on results presented at the European Society for Medical Oncology Congress, “there is absolutely no difference in the objective response rates for GP2013 and rituximab,” the primary endpoint of the trial, reported Wojciech Jurczak, MD, PhD, head of lymphoma, department of hematology, Jagiellonian University, Krakow, Poland.

Dr. Jurczak characterized the double-blind, randomized phase 3 trial ASSIST_FL (NCT01419665) as the “largest biosimilar trial in hematology.” For the study, 629 patients with previously untreated, advanced-stage follicular lymphoma were randomized to GP2013 and the conventional regimen of cyclophosphamide, vincristine, and prednisone (G-CVP) or rituximab and the same three-agent regimen (R-CVP). Each regimen was given for eight cycles followed by maintenance monotherapy with the assigned monoclonal antibody for up to 2 years.

The primary endpoint, objective response rate (ORR), was 87.1% and 87.5% for G-CVP and R-CVP, respectively. There were no differences in ORR among the subgroups evaluated, which included patients aged 60 years and older vs. younger patients, presence or absence of bulky disease, high or low FLIPI (Follicular Lymphoma International Prognostic Index) score, gender, and the geographic region where treatment was given.

Safety was a secondary endpoint evaluated at the end of eight cycles and again after a year of maintenance therapy. The proportion of patients with any adverse event and the proportion with grade 3 or greater adverse events were not statistically different at any time point. There were also no significant differences in any of the other secondary endpoints evaluated, which included pharmacokinetic, pharmacodynamic, and immune measures.

The results are consistent with those of a related randomized bioequivalence trial comparing GP2013 and rituximab in 312 patients with rheumatoid arthritis (Ann Rheum Dis. 2017;76:1598-1602). The primary endpoint in that trial was area-under-the-curve serum concentration time.

The two studies are mutually reinforcing, and “the ASSIST_FL trial ends the story. We have the totality of evidence that GP2013 can be considered a biosimilar,” said Dr. Jurczak, who anticipates “major price differences” for this agent relative to rituximab.

“We may, based on the results of the follicular lymphoma trial, use the biosimilar in all registered indications for rituximab,” said Dr. Jurczak. This is also the conclusion of the European Medicine Agency, which approved this agent in June 2017 for all rituximab indications.

In explaining the process for approval of biosimilars, Dr. Jurczak emphasized that demonstrating bioequivalence is not the same as the approval process for a new therapeutic agent, for which regulatory agents require a demonstration of efficacy on a meaningful clinical endpoint, such as progression-free survival. For biosimilars, it is not necessary to show clinical benefits. Biosimilars must demonstrate the same biological activity, and ORR is considered an acceptable measure.

The ESMO-invited discussant, Michele Ghielmini, MD, PhD, medical director at the Oncology Institute of Southern Switzerland, Bellinzona, agreed. “We can reasonably speculate that (when rituximab and the biosimilar are associated with the same) response rate, they will lead to the same clinical benefits.”

MADRID – The biosimilar GP2013 met the criteria for therapeutic equivalence to rituximab in a large comparator trial of previously untreated patients with aggressive follicular lymphoma.

Based on results presented at the European Society for Medical Oncology Congress, “there is absolutely no difference in the objective response rates for GP2013 and rituximab,” the primary endpoint of the trial, reported Wojciech Jurczak, MD, PhD, head of lymphoma, department of hematology, Jagiellonian University, Krakow, Poland.

Dr. Jurczak characterized the double-blind, randomized phase 3 trial ASSIST_FL (NCT01419665) as the “largest biosimilar trial in hematology.” For the study, 629 patients with previously untreated, advanced-stage follicular lymphoma were randomized to GP2013 and the conventional regimen of cyclophosphamide, vincristine, and prednisone (G-CVP) or rituximab and the same three-agent regimen (R-CVP). Each regimen was given for eight cycles followed by maintenance monotherapy with the assigned monoclonal antibody for up to 2 years.

The primary endpoint, objective response rate (ORR), was 87.1% and 87.5% for G-CVP and R-CVP, respectively. There were no differences in ORR among the subgroups evaluated, which included patients aged 60 years and older vs. younger patients, presence or absence of bulky disease, high or low FLIPI (Follicular Lymphoma International Prognostic Index) score, gender, and the geographic region where treatment was given.

Safety was a secondary endpoint evaluated at the end of eight cycles and again after a year of maintenance therapy. The proportion of patients with any adverse event and the proportion with grade 3 or greater adverse events were not statistically different at any time point. There were also no significant differences in any of the other secondary endpoints evaluated, which included pharmacokinetic, pharmacodynamic, and immune measures.

The results are consistent with those of a related randomized bioequivalence trial comparing GP2013 and rituximab in 312 patients with rheumatoid arthritis (Ann Rheum Dis. 2017;76:1598-1602). The primary endpoint in that trial was area-under-the-curve serum concentration time.

The two studies are mutually reinforcing, and “the ASSIST_FL trial ends the story. We have the totality of evidence that GP2013 can be considered a biosimilar,” said Dr. Jurczak, who anticipates “major price differences” for this agent relative to rituximab.

“We may, based on the results of the follicular lymphoma trial, use the biosimilar in all registered indications for rituximab,” said Dr. Jurczak. This is also the conclusion of the European Medicine Agency, which approved this agent in June 2017 for all rituximab indications.

In explaining the process for approval of biosimilars, Dr. Jurczak emphasized that demonstrating bioequivalence is not the same as the approval process for a new therapeutic agent, for which regulatory agents require a demonstration of efficacy on a meaningful clinical endpoint, such as progression-free survival. For biosimilars, it is not necessary to show clinical benefits. Biosimilars must demonstrate the same biological activity, and ORR is considered an acceptable measure.

The ESMO-invited discussant, Michele Ghielmini, MD, PhD, medical director at the Oncology Institute of Southern Switzerland, Bellinzona, agreed. “We can reasonably speculate that (when rituximab and the biosimilar are associated with the same) response rate, they will lead to the same clinical benefits.”

MADRID – The biosimilar GP2013 met the criteria for therapeutic equivalence to rituximab in a large comparator trial of previously untreated patients with aggressive follicular lymphoma.

Based on results presented at the European Society for Medical Oncology Congress, “there is absolutely no difference in the objective response rates for GP2013 and rituximab,” the primary endpoint of the trial, reported Wojciech Jurczak, MD, PhD, head of lymphoma, department of hematology, Jagiellonian University, Krakow, Poland.

Dr. Jurczak characterized the double-blind, randomized phase 3 trial ASSIST_FL (NCT01419665) as the “largest biosimilar trial in hematology.” For the study, 629 patients with previously untreated, advanced-stage follicular lymphoma were randomized to GP2013 and the conventional regimen of cyclophosphamide, vincristine, and prednisone (G-CVP) or rituximab and the same three-agent regimen (R-CVP). Each regimen was given for eight cycles followed by maintenance monotherapy with the assigned monoclonal antibody for up to 2 years.

The primary endpoint, objective response rate (ORR), was 87.1% and 87.5% for G-CVP and R-CVP, respectively. There were no differences in ORR among the subgroups evaluated, which included patients aged 60 years and older vs. younger patients, presence or absence of bulky disease, high or low FLIPI (Follicular Lymphoma International Prognostic Index) score, gender, and the geographic region where treatment was given.

Safety was a secondary endpoint evaluated at the end of eight cycles and again after a year of maintenance therapy. The proportion of patients with any adverse event and the proportion with grade 3 or greater adverse events were not statistically different at any time point. There were also no significant differences in any of the other secondary endpoints evaluated, which included pharmacokinetic, pharmacodynamic, and immune measures.

The results are consistent with those of a related randomized bioequivalence trial comparing GP2013 and rituximab in 312 patients with rheumatoid arthritis (Ann Rheum Dis. 2017;76:1598-1602). The primary endpoint in that trial was area-under-the-curve serum concentration time.

The two studies are mutually reinforcing, and “the ASSIST_FL trial ends the story. We have the totality of evidence that GP2013 can be considered a biosimilar,” said Dr. Jurczak, who anticipates “major price differences” for this agent relative to rituximab.

“We may, based on the results of the follicular lymphoma trial, use the biosimilar in all registered indications for rituximab,” said Dr. Jurczak. This is also the conclusion of the European Medicine Agency, which approved this agent in June 2017 for all rituximab indications.

In explaining the process for approval of biosimilars, Dr. Jurczak emphasized that demonstrating bioequivalence is not the same as the approval process for a new therapeutic agent, for which regulatory agents require a demonstration of efficacy on a meaningful clinical endpoint, such as progression-free survival. For biosimilars, it is not necessary to show clinical benefits. Biosimilars must demonstrate the same biological activity, and ORR is considered an acceptable measure.

The ESMO-invited discussant, Michele Ghielmini, MD, PhD, medical director at the Oncology Institute of Southern Switzerland, Bellinzona, agreed. “We can reasonably speculate that (when rituximab and the biosimilar are associated with the same) response rate, they will lead to the same clinical benefits.”