Rituximab Biosimilar Ruxience Approved in Europe

Igor Aurer, MD, PhD

The European Commission (EC) has approved the rituximab (Rituxan, US; MabThera, EU) biosimilar Ruxience (PF-05280586) for the treatment of patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris.¹

In making its decision, the EC reviewed a comprehensive data package demonstrating biosimilarity with PF-05280586 to reference rituximab, including results from the REFLECTIONS B3281006 study that evaluated the efficacy, safety and immunogenicity, pharmacokinetics, and pharmacodynamics of PF-05280586. Results showed that there were no clinically meaningful differences in safety or efficacy between the biosimilar and standard rituximab in patients with CD20-positive, low tumor burden follicular lymphoma.²

“The approval of biosimilars such as Ruxience is an important development for the treatment of certain cancers and autoimmune conditions,” Igor Aurer, MD, PhD, professor of Medicine and Head of Hematology Division, University Hospital Centre Zagreb, Croatia, said in a press release. “It’s a step toward allowing clinicians an additional treatment option which can help improve access for patients in need of this established medicine.”

In July 2019, the FDA approved PF-05280586 (rituximab-pvvr) for the treatment of adult patients with CD20-positive B-cell NHL as a single agent or in combination with chemotherapy, or for patients with CD20-positive CLL in combination with chemotherapy. It was also the first biosimilar approved to treat patients with GPA and MPA.

In the REFLECTIONS B3281006 study, patients with previously untreated CD20-positive, low tumor burden follicular lymphoma were randomized 1:1 to receive intravenous PF-05280586 or rituximab-sourced from the European Union (rituximab-EU) at 375 mg/m² once weekly for 4 weeks on days 1, 8, 15 and 22. Patients were stratified at randomization using the Follicular Lymphoma International Prognostic Index 2 (FLIPI2) classification and had an ECOG performance status of 0 or 1.

The primary endpoint was overall response rate (ORR) at week 26, which was defined as the percentage of patients achieving complete response (CR) or partial response (PR), based on central review. Secondary endpoints included progression-free survival (PFS), CR rate at week 26, time to treatment failure, duration of response, overall survival, safety, immunogenicity, pharmacokinetics and pharmacodynamics. The primary endpoint was evaluated once all patients completed week 26 assessments.

A total 394 patients were randomized to receive PF-05280586 (n = 196) or rituximab-EU (n = 198). Moreover, 54.8% of patients were female, the median age was 60.0 years, and 28.4% had low, 66.0% medium, and 5.6% had high risk, according to FLIPI2. Additionally, 26.9% of subjects had Ann Arbor Stage II, 44.2%, Stage III, and 28.9%, Stage IV disease.

Results showed that the ORR at week 26 was 75.5% with the biosimilar compared with 70.7% for rituximab-EU for a difference of 4.66%; moreover, the corresponding 95% CI (-4.16—13.47) was within the prespecified equivalence margin of ±16%. The CR rates were 29.3% vs 31.0% with the biosimilar and rituximab-EU arms, respectively.

Updated findings showed that the estimated 1-year PFS rates were 78.2% (95% CI: 70.2-84.2) and 83.0% (95% CI: 75.0-88.6) in the PF-05280586 and rituximab-EU groups, respectively.³

Regarding safety, the incidence of treatment-emergent adverse events (TEAEs) were similar at 78.6% with PF-05280586 versus 72.1% with rituximab-EU. The most frequently reported TEAEs included infusion-related reactions (25.5% vs 29.9% with PF-05280586 and rituximab-EU, respectively), pruritus (6.6% vs 11.2%) and headache (8.2% vs. 9.6%). Serious AEs were similar at 7.7% and 6.6% with PF-05280586 and rituximab-EU, respectively.

The most common adverse events associated with PF-05280586 include infusion-related reactions, fever, lymphopenia, neutropenia, chills, infection, weakness, nausea, diarrhea, headache, muscle spasms, anemia, and peripheral edema. Similar to standard rituximab, the FDA label for the biosimilar includes a Boxed Warning for increased risks of the following: fatal infusion-related reactions; severe skin and mouth reactions; hepatitis B virus reactivation; and progressive multifocal leukoencephalopathy.

In the United States, PF-05280586 was introduced to the US market in January 2020 and was launched at a WAC of $71.68 per 10 mg, which translates to a 24% discount to the WAC of the reference product.

References

1. PFIZER RECEIVES EUROPEAN APPROVAL FOR ONCOLOGY BIOSIMILAR, RUXIENCE™ (RITUXIMAB). Published April 2, 2020. https://bit.ly/2XazlWi. Accessed April 2, 2020. 
2. 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: 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, CA. Abstract 394.
3. Sharman JP, Liberati AM, Ishizawa K, et al. A randomized, double-blind, efficacy and safety study of PF-05280586 (a rituximab biosimilar) compared with rituximab reference product (MabThera^®) in subjects with previously untreated CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL) [published online ahead of print December 9, 2019]. BioDrugs. doi: 10.1007/s40259-019-00398-7