Ruxience

Product Profile:

Rituximab-pvvr (Ruxience) 

Drug Category: Monoclonal anti-CD20 antibody

Target Indications:  Treatment of adult patients with relapsed or refractory, low-grade or  follicular B-cell non-Hodgkin’s lymphoma who are CD20-positive and have failed prior treatments; patients who have nonprogressing, low-grade, CD20-positive B-cell non-Hodgkin’s lymphoma and who are stable after receiving a prior chemotherapy regimen containing cyclophosphamide, vincristine and prednisone;  patients with CD20-positive follicular lymphoma who are therapy naïve in combination with chemotherapy or who had responded to previous rituximab therapy; patients with CD20-positive chronic lymphocytic leukemia in combination with fludarabine and cyclophosphamide; and granulomatosis with polyangiitis in adult patients in combination with glucocorticoids

Developed by Pfizer and will be marketed by Pfizer

Summary:  Ruxience is the second FDA-approved biosimilar version of rituximab (reference product, Rituxan) manufactured by Genentech.

Originally designated PF-05280586, Pfizer submitted a biologic license application for approval via the 351(k) biosimilar pathway in September 2018. The Food and Drug Administration (FDA) approved the application on July 23, 2019 (without recommendation from the FDA’s Oncology Drug Advisory Committee. 

Like the first biosimilar approved for rituximab, Teva and Celltrion’s Truxima, Ruxience was not approved for the reference product’s autoimmune indications (e.g., rheumatoid arthritis). However, Pfizer did complete clinical trials in the use of PF-05280586 in rheumatoid arthritis. This drug is not yet marketed; a launch date has not been announced.

About the Manufacturer

Pfizer entered the biosimilar market through two avenues: (1) its acquisition of Hospira and (2) its own internal pipeline development. Pfizer was established in 1849, and it is headquartered in New York City. It has a considerable portfolio of biosimilar products approved by the FDA and in various stages of filing. In addition to Ruxience, its approved biosimilars include Inflectra, the first biosimilar version of Remicade; Ixifi, another version of Remicade that will be sold overseas only; Trazimera, a biosimilar trastuzumab; Retacrit, a biosimilar epoetin that was approved in May 2018; Zirabev, a biosimilar bevacizumab that was approved in June 2019; and Nevistym, a biosimilar version of filgrastim that is also marketed. Pfizer’s biosimilar pipeline consists of a biosimilar adalimumab in phase 3 trials and a biosimilar pegfilgrastim in phase 1 development.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Truxima was the first rituximab biosimilar to be approved by the FDA. This product has not yet entered the marketplace.  Pfizer received approval for its agent Ruxience in July 2019; launch plans for this product is not yet announced. Boehringer Ingelheim and Sandoz both had biosimilars of rituximab in Phase III development but made business decisions to not move forward with the products.

Although these two biosimilars were approved for the non-autoimmune indications of the reference product Rituxan, it is not clear as to whether payers will exclude coverage for the nonapproved uses. However, Amgen/Allergan’s investigational biosimilar also has undergone clinical testing for rheumatoid arthritis as well as non-Hodgkins lymphoma. 

Rituximab Biosimilar(s) in Development

Company Name Product Name Brand Name Stage of Development

Amgen/Allergan

ABP798

TBD

Phase III trial  completed in June 2019 for NHL

Phase III trial for rheumatoid arthritis was completed in October 2018

Mabion/Mylan

MabionCD20

TBD

Met with FDA in July 2018 to finalize “ the most optimal pathway towards registering” in the US; Filed for EMA approval in June 2018

       

 

The Biosimilar Mabs Have It: FDA Approves Biosimilars for Adalimumab and Rituxumab

(July 24, 2019) On July 22, 2019, the Food and Drug Administration (FDA) announced the approval of Pfizer’s Ruxience, a biosimilar of rituximab. Compared with reference agent MabThera, this biosimilar proved to produce equivalent efficacy and safety in a phase 3 trial.

Pfizer Signs Patent Settlement With Roche on Rituximab Biosimilar

(March 25, 2019) An agreement was announced between Pfizer and Roche (Genentech), which concludes litigation over a key patent for Rixutan. This may affect when Pfizer decides on marketing the product.

Amgen and Allergan Announce Top-Line Results of Phase 1/3 Rituximab Biosimilar Trial

(January 24, 2019) The results demonstrate that the study met its primary endpoint of pharmacokinetic (PK) similarity. Additionally, equivalent efficacy was established and a similar safety profile was demonstrated.

Rituximab Biosimilar Approved by FDA for Cancer Treatment

(November 28, 2018) On November 28, 2018, the Food and Drug Administration (FDA) announced the approval of rituximab-abbs (Truxima™), produced by Celltrion and marketed by Teva. Approval for this rituximab biosimilar was overwhelmingly recommended by the FDA’s Oncology Drug Advisory Committee by a vote of 16-0 in October.

Sandoz Decides Against Marketing Rituximab Biosimilar in US

(October 30, 2018) Sandoz announced that it would halt its efforts to obtain approval for its biosimilar version of rituximab from the US Food and Drug Administration (FDA).

Celltrion's Rituximab Biosimilar Earns Positive FDA Review

(October 8, 2018) The information package released by reviewers for the Food and Drug Administration (FDA) indicates that a positive recommendation for Celltrion’s rituximab biosimilar is likely at the Advisory Committee meeting on October 10.

Celltrion Bounces Back, Resubmits for FDA Approval of Rituximab Biosimilar

(May 30, 2018) Anticipating that its issues with the Incheon, South Korea, manufacturing plant will be resolved, Celltrion has resubmitted its biologic license application for a rituximab biosimilar (CT-P10).

FDA Hands Sandoz a Rejection on Its Rituximab Biosimilar

(May 2, 2018) Sandoz announced today that the Food and Drug Administration (FDA) has decided not to approve its biosimilar version of the oncology biosimilar rituximab.

Teva and Celltrion Receive Rejections on Trastuzumab and Rituximab Biosimilars

(April 5, 2018) Celltrion and its partner Teva were dealt a significant blow today, as the Korean manufacturer announced that the latest two biosimilar candidates were rejected by the Food and Drug Administration.

Biosimilar Rituximab Under FDA Review

(July 5, 2017) Celltrion announced June 30, 2017 that it has submitted its 351(k) application to the Food and Drug Administration for approval of its biosimilar version of rituximab. This represents the first biosimilar application for rituximab, a monoclonal antibody to CD20..

Celltrion’s Rituximab Recommended for Approval in Europe

(January 3, 2017) Just weeks after Celltrion presented data at the American College of Rheumatology meeting demonstrating that its product CT-P10 is as safe and effective as Rituxan®for the treatment of rheumatoid arthritis (RA), the European Medicines Agency (EMA) received the recommendation to approve the product for use in the EU.

CT-P10 Rituximab Biosimilar Phase 3 Clinical Trial Results Announced

(September 28, 2016) The results of a phase 3 trial presented at the American College of Rheumatology meeting proved that a biosimilar version of Rituxan provided equivalent results over a 24-week study period compared with the originator product.

Prognosis of Patients with B-Cell non-Hodgkins Lymphoma

Will Biosimilar Rituximab Replace the Originator Product?

Clinical Trials of Ruxience

Phase 3 Trial

Pfizer performed one phase 3 clinical trial to test Ruxience’s efficacy and safety compared with the reference product in the treatment follicular lymphoma. A phase 2 clinical trial was also conducted to evaluate its effectiveness in the treatment of rheumatoid arthritis, but this indication was not pursued by Pfizer. 

A Study Of PF-05280586 (Rituximab-Pfizer) Or MabThera® (Rituximab-EU) For The First-Line Treatment Of Patients With CD20-Positive, Low Tumor Burden, Follicular Lymphoma (REFLECTIONS B328-06)

A total of 394 adult patients with a confirmed diagnosis of low-tumor-burden follicular lymphoma (stages II–IV) were enrolled in a randomized, double-blind, parallel-group study. None of the patients received rituximab treatment in the past. The patients received monotherapy with either the biosimilar PF-5280586 (Ruxience) (196 patients) or EU-licensed rituximab (brand name MabThera) (198 patients). All participants received dosages of 375 mg/m2 on treatment days 1, 8, 15, and 22.

The primary outcomes measure was overall response rate at week 26. Secondary efficacy outcomes measures included complete remission at week 26, duration of response up to 52 weeks, overall survival, and time to treatment failure. Additional safety-related secondary outcomes measures included were treatment-emergent adverse events and serious adverse events up to 52 weeks after trial initiation, patients with significant laboratory abnormalities. The researchers also evaluated immunogenicity outcomes.

Based on the prespecified benchmarks of equivalent efficacy set by the investigators, they determined that the biosimilar’s clinical outcomes were equivalent (see Table below) to those of the reference product.

Results (after 24 wk)

PF-052805586

(N=196)

EU-Licensed Rituxan

(N=198)

ORR

75.5%

70.7%

CR

29.3%

30.4%

Overall Survival (median)

N/A

18.9 mo

1-year PFS

76.4%

81.2%

TEAEs

79.6%

73.6%

Severe AEs

8.7%

7.6%

The percentage of patients with treatment-emergent adverse events (TEAEs) were similar in both treatment groups, as well as those with severe AEs. The types of AEs experienced were similar for both the patients receiving the biosimilar and the reference product.

In terms of immunogenicity, 22.1% of patients receiving the biosimilar tested positive for antidrug antibodies, compared with 19.8% of those taking EU-licensed Rituxan. Of those testing positive for antidrug antibodies, no one in either subgroup tested positive for neutralizing antibodies.

Based on these results, the investigators concluded that the biosimilar did not provide inferior clinical or safety outcomes compared with the reference agent.

Phase 1/2 Trial

Comparative assessment of clinical response in patients with rheumatoid arthritis between PF‐05280586, a proposed rituximab biosimilar, and rituximab

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