Product Profile: Retacrit

Product Profile:

Epoetin alfa-epbx (Retacrit)

Drug Category: Erythropoiesis-stimulating agent

Target Indications: Anemia caused by chronic kidney disease in patients on dialysis or not on dialysis, related to cancer chemotherapy, related to zidovudine use in patients with HIV infection; and after elective surgery to reduce the chance that red blood cell transfusions will be required because of blood loss.

Manufactured and marketed by Pfizer

Summary: Retacrit is a biosimilar version of epoetin (reference products, Epogen (epoetin alfa, Amgen, Inc.) and Procrit (epoetin alfa, Janssen) manufactured by Pfizer. This biosimilar was originally developed and sold in Europe by Hospira (which was acquired by Pfizer) under the nonproprietary name of epoetin zeta.

A biologic license application for approval via the 351(k) biosimilar pathway was submitted to the Food and Drug Administration (FDA) in December 2014; was recommended for approval in May 2017 and rejected in June 2017 due to manufacturing issues; and then approved in May 2018. Pfizer launched Retacrit in November 2018, at a significant discount compared to the wholesaler acquisition cost of the reference products. Vifor Pharma will market the drug in the dialysis market while Pfizer will market the drug for all other indications.

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 Retacrit, its approved biosimilars include Inflectra, the first biosimilar version of Remicade; Ixifi, another version of Remicade that will be sold overseas only; and Nivestym, a biosimilar filgrastim that was approved in 2018. Pfizer’s biosimilar pipeline consists of a biosimilar trastuzumab, bevacizumab, and rituximab, all being filed for approval with the FDA; biosimilar adalimumab in phase 3 trials; and biosimilar pegfilgrastim in phase 1 development.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Pfizer began selling Retacrit at a wholesale acquisition cost discount of 33.5% to Epogen and a 57% discount to Procrit.  It is the first biosimilar version of epoetin sold in the US. In contrast, five biosimilars of epoetin were approved by the European Medicines Agency.

A search for other late-stage biosimilar candidates that may potentially to seek approval in the US yielded no results. For example, Sandoz, which markets Biocrit in the EU, does not list epoetin in its US pipeline. The total epoetin alfa market was about $1.8 billion in 2017. Darbepoetin alfa (Aranesp by Amgen) does compete for prescriptions with epoetin, and several biosimilar manufacturers (e.g., Apobiologix) is involved in early-stage research on this product. Amgen has been seeing decreasing sales of both originator biologic products in recent years.

Pfizer Launches Retacrit, First Biosimilar Version of Epogen and Procrit

(November 14,, 2018) Pfizer began marketing its biosimilar version of epoetin alfa. Pfizer launches Retacrit® at a 33.5% discount to Amgen’s reference product Epogen®.

Part B to Part D and Other Questions: How CMS’s Plans Could Affect Biosimilars

(August 10, 2018)  Some of these tactics are a bit late to the party, as commercial insurers and health plans have been employing them for years. To the extent that an injectable treatment can be managed through the pharmacy benefit rather than the medical benefit, the drug can be easily subjected to prior authorization, step therapy, quantity limits, and other tools routinely used.

Pfizer Gets FDA’s Green Light on Its Filgrastim Biosimilar

(July 21, 2018)  On July 20, the US Food and Drug Administration (FDA) approved the second biosimilar version of filgrastim. Pfizer’s filgrastim biosimilar is named Nivestym™(filgrastim-aafi).

Convincing Two Main Providers the Key to Pfizer’s Retacrit Success

(June 1, 2018) Not only does Retacrit® need to pass muster with payers like health plans and insurers, which we assume it will, but Retacrit will need to be accepted by the two 800-pound gorillas of the kidney dialysis field.

Pfizer Gets Green Light From the FDA on Epogen® Biosimilar

(May 15, 2018) Pfizer finally earned approval from the U.S. Food and Drug Administration (FDA) on the first biosimilar version of Epogen®. The drug, Retacrit® (epoetin alfa-epbx), had originally been submitted for approval in December 2014. Its much stalled road to approval is finally at an end.

More Clinical Study Evidence That Biosimilar Switching Carries a Low Risk

(March 6, 2018) A literature review published this past weekend in Drugs reaffirms what most parties interested in biosimilars suspect—that switching from a reference product to biosimilar is not a significant clinical concern. Biosimilar switching was not generally associated with poorer outcomes.

FDA Stuns With Rejection of Pfizer’s Retacrit

(June 26, 2017) Following a 14-1 vote by its Oncology Drug Advisory Committee last month to recommend approval for Pfizer’s biosimilar version of Epogen®, the Food and Drug Administration (FDA) on June 22 sent the drug maker a complete response letter outlining its decision to reject the product.

The Role of Epoetin in Red Cell Production

What Is Chemotherapy-Induced Anemia?

Clinical Trials of Retacrit

Published Trial Results

There were two clinical trials reviewed for the FDA approval of Retacrit. Both of these trials included patients with chronic kidney disease.

Retacrit EPOE-10-13 study

Retacrit EPOE-10-01 study

 

Chronic Kidney Disease

SQ Dosing Study.  Patients with chronic kidney disease undergoing dialysis participated in a 16-week double-blind, randomized study to compare epoetin zeta (EU biosimilar) with the reference produce epoetin alfa. The 16-week study had a primary endpoints of the mean weekly dose of epoetin per kilogram of body weight that maintained a mean hemoglobin levels with the target range of 9.0 to 11.0 g/dL during the last four weeks of treatment. Equivalency was achieved when the hemoglobin levels were within the 9.0 to 11.0 g/dL and had a pre-specified 95% confidence interval (CI) for the least-squares (LS) mean of the difference when it was within -0.5 and 0.5 g/dL and when the dosing was within the pre-specified equivalence limits of -45 U/kg/wk and 45 U/kg/wk. The original study design was for a 95% CI and the FDA requested a 90% CI. Eligible patients could enroll in an extension study for 48 weeks.

Results in the Intent-to-treat population:

 
Epoetin Zeta
N=124
Epoetin alfa
N=122
Difference
Mean Weekly Hemoglobin (g/dL)
10.16
(SE 0.073)
10.12
(SE 0.074)
0.04
(SE 0.104)
Mean Weekly Dose (U/kg)
79.57
SE 4.356
81.91
SE 4.373
-2.34
SE 6.175

Blood transfusions were required in 4% of the study participants in each of the study arms.

IV Dosing Study. The same study design, endpoints and equivalency requirements were the same as in the subcutaneous study with the study having a duration of 24 weeks.

Results in the Intent-to-treat population:

 
Epoetin zeta
N=306
Epoetin alfa
N=306
Difference
Mean Weekly Hemoglobin g/DL
10.17
(SE 0.047)
10.28
(SE 0.047)
-0.12
SE 0.104
Mean Weekly Dose (U/kg)
90.16
(SE 3.87)
89.79
(SE 3.88)
0.37
(SE 5.48)

Blood transfusions were required in 6% of the study participants in each of the study arms. Eligible patients were able to enroll in a 48-week extension trial.

Safety

The safety results for the two studies were pooled (including the extension studies). The incidence of >1 treatment emergent adverse event were similar in both groups (321 patients in the epoetin zeta group [75.9%] vs. 318 patients [74.6%] in the epoetin alfa group). More patients in the reference product group had ≥1 severe adverse event (116 [27.2%] vs. 101 [23.9%, respectively]). A slightly greater percentage of study participants discontinued the study drug due to a treatment-emergent adverse event in the biosimilar product group compared with the Epogen group (15 [3.5%] vs. 13 [3.1%]).

Most frequently reported treatment-emergent adverse events:

Epoetin zeta
Epoetin alfa
Nausea
9.5%
7.7%
Arteriovenous fistula site complication
7.6%
7.0%
Vomiting
7.6%
4.9%

In both groups, 4 patients tested positive for an anti-drug antibody (ADA) during the studies. None of the patients tested positive for neutralizing antibodies against recombinant human epoetin (rhEPO).

Current ongoing trial: Post-Authorization Safety Cohort Observation of RetacritTM (Epoetin Zeta) Administered Subcutaneously for the Treatment of Renal Anaemia (PASCO II)

Anemia Associated with Chemotherapy

Biosimilar Retacrit (epoetin zeta) in the treatment of chemotherapy-induced symptomatic anemia in hematology and oncology in German (ORHEO) – non-interventional study

Important Links and Resources

Information About Biosimilars

Patient Assistance Information

Additional Patient Assistance Information

US Biosimilar Filings Status

Copyright 2018 by SM Health Communications. All rights reserved.

We are pleased to hear your questions or comments, which should be provided through our contact us page.