SAN DIEGO — A rituximab biosimilar demonstrated noninferiority to European (EU)-licensed rituximab (MabThera) in a randomized trial involving patients with low-tumor burden follicular lymphoma.
The biosimilar PF-05280586 from Pfizer led to an objective response rate of 75.5% at 26 weeks as compared with 70.7% for patients treated with rituximab-EU. The estimated 1-year progression-free survival (PFS) did not differ significantly between treatment arms, but was numerically higher with rituximab-EU (81.2% vs 76.4%).
Treatment-emergent adverse events (TEAEs), serious TEAEs, and grade 3 TEAEs occurred in a similar proportion of patients in each treatment group, Jeff Sharman, MD, of Willamette Valley Cancer Institute and Research Center in Eugene, Oregon, reported here at the American Society of Hematology meeting.
“The primary endpoint was met; there were no clinically meaningful differences in progression-free survival between the treatment groups,” said Sharman. “There was a rapid depletion in CD19-positive B cell counts, following initial dosing, with similar results in both treatment groups, followed by recovery. The safety profile of PF-05280586 was similar to the established safety profile of rituximab.”
He added that the immunogenicity, pharmacokinetics, and pharmacodynamics were similar between the two.
“These results confirm the biosimilarity of PF-05280586 with rituximab-EU,” he said.
As Sharman noted before presenting the results of the trial, a biosimilar is a biologic drug that is highly similar to a licensed product. The U.S. and EU define biosimilarity differently, but both definitions incorporate the same underlying principles. Regulatory approval of a biosimilar is based on the totality of data supporting biosimilarity. Biosimilars are expected to offer cost savings and improve access to biologic agents.
Investigators in the U.S., Europe, and South America enrolled patients in a randomized trial to compare PF-05280586 and rituximab-EU with respect to efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics. Eligible patients had untreated CD20-positive low-tumor burden follicular lymphoma. The agents were administered weekly for 4 weeks.
Follow-up continued for 52 weeks, and the primary endpoint was overall response rate (complete and partial response) after 26 weeks. According to the trial design, the two drugs would be considered therapeutically equivalent if the difference in response rate was with a margin of ±16% (per U.S. and EU regulatory agreement).
Data analysis included 394 randomized patients, who had a median age of 60. By Follicular Lymphoma International Prognostic Index (FLIPI) criteria, 28.4% of patients had low-risk lymphoma, 66.0% had medium-risk, and 5.6% had high-risk. By Ann Arbor staging criteria, 26.9% had stage II disease, 44.2% had stage III, and 28.9% had stage IV.
Analysis of objective response at 26 weeks produced a nonsignificant difference between the treatment groups. The 4.66% between-group difference and associated 95% CI (-4.16% to 13.47%) fell within the prespecified margin for equivalence.
The overall response rates included complete responses in 29.3% and 30.4% of the PF-05280586 and rituximab-EU groups, respectively. An additional 11.5% of the biosimilar-treated patients and 19.6% of the rituximab-EU group had stable disease at 26 weeks.
The incidence of TEAEs was 78.6% in the biosimilar group and 72.1% with rituximab-EU. The most commonly reported TEAEs with PF-05280586 and rituximab-EU were infusion-related reactions (25.5% vs 29.9%), pruritus (6.6% vs 11.2%), and headache (8.2% vs 9.6%). The incidence of serious TEAEs was 7.7% with the biosimilar and 6.6% with rituximab-EU.
The incidence of grade 3 TEAEs was similar between groups (13.8% with biosimilar vs 12.7%).
Depletion of CD19-positive B-cell counts occurred rapidly after initial dosing in both groups, followed by recovery at week 39 or earlier, and then sustained increases to week 52. Mean serum concentrations of the drugs were similar, including no major differences in mean serum concentrations between anti-drug antibody (ADA)-positive and ADA-negative patient subgroups.
In response to questions that followed his presentation, Sharman said the decision to choose rituximab-EU over the U.S.-licensed agent was made because of the global nature of the trial. He added that he was unaware of any substantive differences between the two licensed products.
When asked about the decision to conduct a trial of monotherapy as opposed to chemoimmunotherapy, Sharman said that the low-tumor burden population enrolled in the trial was considered appropriate for monotherapy and would result in a “cleaner” evaluation of PF-05280586 without potential confounding by the effects of chemotherapy.
Clinical development of PF-05280586 occurs in an increasingly crowded biosimilar market. The FDA approved the first U.S. biosimilar for rituximab late last month, while EU regulatory authorities have approved a half-dozen rituximab biosimilars.
The study was supported by Pfizer.
Sharman disclosed relationships with Acerta, Pharmacyclics, Pfizer, TG Therapeutics, Abbvie, and Genentech.