FDA Approves Pfizer's Rituximab Biosimilar, Ruxience

This article has been updated.

The FDA has approved Pfizer’s rituximab biosimilar, Ruxience (rituximab-pvvr), referencing Rituxan. The biosimilar was approved to treat non-Hodgkin lymphoma, chronic lymphocytic leukemia, and granulomatosis with polyangiitis and microscopic polyangiitis.

The fact that the biosimilar was not approved for all indications of its reference, a Pfizer representative told The Center for Biosimilars^® in an email, is due to the fact that “Genentech has exclusivity for rituximab in certain indications. Pfizer has agreed to the terms of a global settlement,” but “specific terms and conditions of the settlement are confidential.”

“Biosimilars like Ruxience have the potential to deliver real value in healthcare, improving access to and affordability of an important cancer treatment which could help more patients receive optimal care,” said Andy Schmeltz, global president of Pfizer Oncology, in a statement. “The FDA approval marks our third oncology biosimilar to be approved in the US this year, reinforcing our commitment to bring these important medicines to patients living with cancer.”

While it was not granted an indication in rheumatoid arthritis (RA), the biosimilar was studied in a phase 1 trial comparing its pharmacokinetics (PK) versus EU- and US-licensed reference rituximab, MabThera and Rituxan, respectively, in 220 patients with active RA.¹ The PK profiles of all 3 rituximab products were similar, and all resulted in sustained, profound B cell suppression up to week 25. The incidence of antidrug antibodies was similar across all 3 study arms, and no clinically meaningful differences in adverse events was noted.

In an extension study among 185 patients who completed 16 or more weeks of the PK trial, patients were given up to 3 additional treatments (comprising 2 infusions per course of treatment) with the biosimilar; those who had received the EU- or US-licensed rituximab reference switched their treatment to the biosimilar.² The long-term safety and tolerability was acceptable in all groups up to week 96, with a low incidence of adverse events in all groups. The percentage of patients who achieved low disease activity or remission was similar across all groups at all time points, and responses were sustained until the end of the study.

The biosimilar was also shown to have similar efficacy, safety, immunogenicity, PK, and pharmacodynamics to the reference drug at week 26 in patients with previously untreated CD20-positive, low tumor burden follicular lymphoma.³ The 52-week comparative study in 349 patients who received the biosimilar (n = 196) or the EU-licensed reference product (n = 198) had a primary end point of overall response rate (ORR) at week 26, and overall, the study found that ORR at week 26 was 75.5% in the biosimilar arm compared with 70.7% in the reference arm, for a difference of 4.66%. The corresponding 95% CI, —4.16% to 13.47%, fell within the prespecified equivalence margin of ±16%.

While no launch date has been announced for the biosimilar, earlier this year, Pfizer reached a settlement with Roche concerning a kay patent for the brand-name rituximab.

Ruxiance joins Celltrion and Teva’s Truxima in the ranks of FDA-approved rituximab products, though it is not yet known when Truxima will be marketed in the United States. Truxima was only approved in oncology indications due to patent challenges in the US landscape.

References

1. Cohen S, Emery P, Greenwald M, et al. A phase 1 pharmacokinetics trial comparing PF‐05280586 (a potential biosimilar) and rituximab in patients with active rheumatoid arthritis. Br J Clin Pharamcol. 2016;82(1):129-138. doi: 10.1111/bcp.12916.

2. Cohen SB, Burgos-Vargas R, Emery P, Jin B, Cronenberger C, Vásquez-Abad MD. Extension study of PF-05280586, a potential rituximab biosimlar, versus rituximab in subjects with active rheumatoid arthritis. Arthritis Care Res (Hoboken). 2018;70(11): 1598-1606. doi: 10.1002/acr.23586.

3. Sharman J, Liberati A, Silva R, et al. A randomized, double-blind efficacy and safety study of PF-05280586 (a potential rituximab biosimilar) compared with rituximab reference product (MabThera) in subjects with previously untreated CD20-positive, low tumor burden follicular lymphoma (LTB-FL). Presented at the American Society of Hematology Annual Meeting, December 1-4, 2018; San Diego, California. Abstract 394.