Product Profile: Nivestym

Product Profile:

Filgrastim-aafi (Nivestym)

Drug Category: Granulocyte Colony–Stimulating Factor

Target Indications: Decreasing the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs; reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia;  reducing the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation; mobilizing autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis; reduce the incidence and duration of sequelae of neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.

Manufactured and marketed by Pfizer

Summary: Nivestym is a biosimilar version of filgrastim (reference product, Neupogen, Amgen) manufactured and marketed by Pfizer. Originally designated PF-06881893, this biosimilar was first developed by Hospira (which was subsequently acquired by Pfizer) and approved in Europe in 2010. A US biologic license application for approval via the 351(k) biosimilar pathway was submitted to the Food and Drug Administration (FDA) in Q4 2017, and it was approved in the US on July 20, 2018. Nivestym was the second filgrastim biosimilar approved and marketed in the US.

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 Nivestym, its approved biosimilars include Inflectra, the first biosimilar version of Remicade; Ixifi, another version of Remicade that will be sold overseas only; and Retacrit, a biosimilar epoetin that was approved in May 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

Company

Product name

Brand name

Innovator product

Filing Date

Stage of development

Filgrastim

Sandoz

Filgrastim-sndz

Zarxio

Neupogen

May 2014

FDA approved March 6, 2015; marketed

Teva

Tbo-filgrastim*

Granix*

N/A

2009

FDA approved  August 30, 2012

Adello Biologics

TBD

Neupogen

September 2017

FDA decision expected Q4 2018

Tanvex Biologics

TX-01

TBD

Neupogen

October 2018

FDA decision expected Q3 2019

Apotex (Apobiologix)

TBD

Neupogen

February 2015

No public information on FDA action (CRL issued?)

Pegfilgrastim

Adello Biologics

TPI-120

Neulasta

Application possible in 2018

Apotex (Apobiologix)

Lapelga

Neulasta

December 2014

No public information on FDA action reported (CRL issued?)

Coherus Bioscience

Pegfilgrastim-cbqv

Udenyca

Neulasta

August 2016

Approved November 2, 2018; to be marketed early January 2019

Mylan/Biocon

Pegfilgrastim-jmdb

Fulphila

Neulasta

February 16, 2017

Approved June 4, 2018; marketed

Sandoz

LA-EP2006

TBD

Neulasta

December 2015

CRL issued June/July 2016; withdrew EMA application January 2017; new application possible 2019

*Filed as a 351a product (prior to implementation of 351[k] pathway). Not technically a biosimilar.  CRL = complete response letter.

Tidal Wave of Pegfilgrastim Biosimilars About to Hit Europe

(September 27, 2018) The European Medicines Agency (EMA) has had an extremely busy week in the pegfilgrastim biosimilars arena, granting marketing authorization to two companies’ products. In addition, the EMA’s Committee for Medicinal Products for Human Use has also recommended aprpoval for three others.

Scaling the Mountains to Create a Biosimilar Market Success

(September 11, 2018) The only biosimilar market success story to date, Zarxio®, may be as much the result of a certain set of preconditions as that of Sandoz’s marketing efforts.

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).

A Test for Adello and for FDA’s Biosimilar Approval Pathway

(March 29, 2018) Adello Biologic’s 351(k) application for filgrastim comprises the physiochemical biosimilarity evidence, but in terms of clinical data, only phase 1 studies were performed..

Evidence to Support Zarxio Use Presented at AMCP

(October 27, 2017) Two posters presented at the Academy of Managed Care Pharmacy bolstered the case for moving away from the use of the originator filgrastim product Neupogen.

Coverage Uptake: Zarxio Covered by 94% of Employer-Sponsored Plans

(July 11, 2017) An analysis released by Avalere on July 11 showed that coverage of biosimilar filgrastim is the rule, not the exception, by employer-sponsored plans.

Avoiding Neutropenic Infection: A Nurse's Perspective

Neutropenic Fever

Clinical Trials of Renflexis

Published Trial Results

Note: Nivestym was approved in Europe in 2010. The FDA did not require phase 3 trials comparing this agent with the US-licensed version of Neupogen in its review for approval. The only phase 3 trial associated with this biosimilar that can be located was associated with the EU-licensed version and is described below:

Phase 3 Trial. A phase III randomized equivalence study of biosimilar filgrastim versus Amgen filgrastim in patients receiving myelosuppressive chemotherapy for breast cancer.

This trial was conducted in multiple European centers, comprising 279 patients with breast cancer. Patients were randomized to receive either the reference product Neupogen or the biosimilar version manufactured by Hospira. The study’s primary endpoint was the duration of any severe neutropenia (DSN) episodes that occurred during the first chemotherapy cycle.

All patients in this double-blinded study were deemed eligible for breast cancer treatment with doxorubicin and docetaxel in the neoadjuvant/adjuvant setting or as first-line use in patients with metastatic cancer. Patients received the biosimilar (184 patients) or reference product (95 patients) 5 μg/kg/day.

The investigators found that mean DSN was 1.6 days for those receiving the biosimilar and 1.3 days for those given Neupogen. This signaled bioequivalency according to the predefined study criteria. The secondary endpoints of mean time to absolute neutrophil count recovery and incidence of febrile neutropenia also were deemed similar and proved the biosimilar’s noninferiority to the originator product. Grade 1—2 bone pain were the most common treatment-related adverse event with both filgrastim products.

They concluded that the biosimilar and originator filgrastim products were bioequivalent in terms of efficacy and safety.

Phase 1 Studies. ZIN-FIL-1501 and -1502 evaluated the pharmacodynamics and pharmacokinetics of the US-licensed version; C1121012 evaluated the immunogenicity characteristics of this biosimilar. All of these studies were conducted in healthy subjects. The resulting geometric mean ratios of the maximum concentration levels, area of the plasma concentration–time curve (0 to infinity), average neutrophil maximum concentration, and CD34+ concentrations were well within the prespecified limits, and determined to demonstrate similarity of PK and PD endpoints. The FDA reviewers did not detect clinically meaningful differences in the formation of antidrug antibodies between Nivestym and the US-licensed version of the reference product.

Protocol
Title
Subjects
Objectives
Dose/Route
PK/PD Similarity Study
ZIN-FIL-1502
A randomized, open-label, single-dose, crossover study evaluating the pharmacokinetics and pharmacodynamics of PF-06881893 to US-licensed Neupogen after SC administration to health subjects
Healthy (N = 24)
PK, PD (ANC), and safety
5 mcg/kg/day single SC dose versus US-licensed Neupogen with at least 28 days between treatments
ZIN-FIL-1501
A randomized, open-label, crossover study evaluating the pharmacokinetics and pharmacodynamics of PF-06881893 to US-licensed Neupogen after SC administration to healthy subjects
Healthy (N = 60)
PD (CD34+), PK, and safety
5 mcg/kg/day single SC dose versus US-licensed Neupogen with at least 28 days between treatments
Immunogenicity Study
C1121012
A randomized, open-label, 2-period, parallel arm study to assess the immunogenicity of multiple SC doses of “filgrastim Hospira” or US-licensed Neupogen reference product in healthy subjects
Healthy (N = 256)
Immunogenicity and safety
5 mcg/kg/day consecutive daily SC doses in period 1 followed by a single SC dose in period 2 of PF-06881893 versus US-licensed Neupogen with at least 26 days between treatments

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.