Ziextenzo

Product Profile:

Pegfilgrastim-bmez (Ziextenzo)

Drug Category: Granulocyte colony–stimulating factor

Target Indications: Reduce the incidence of infection in patients with nonmyeloid malignancies receiving myelosuppressive anti‑cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Manufactured and marketed by Sandoz

Summary: Ziextenzo (LA-EP2006) is a biosimilar version of pegfilgrastim (reference product, Neulasta by Amgen) that is manufactured by Sandoz. A biologic license application for approval via the 351(k) biosimilar pathway was originally submitted to the Food and Drug Administration (FDA) in December 2015, with final approval given in November 2019. Sandoz launched the drug immediately following approval. This agent, like all other biosimilar pegfilgrastim candidates, was subject to complete response letters from the FDA. Its 351(k) application was resubmitted in April 2019. Sandoz set its initial price at a 37% discount in wholesale acquisition cost discount relative to Neulasta.

About the Manufacturer

Sandoz, although established as a division of Novartis in 2003, has its origins as an active player in the pharmaceutical industry in 1886. It has a considerable portfolio of biosimilar products approved by the FDA and in various stages of filing.  Besides Ziextenzo, Sandoz has obtained FDA approvals for Zarxio (filgrastim-sndz), Hyrimoz (adalimumab-adaz), and Erelzi (etanercept-szzs). Sandoz has withdrawn its biosimilar rituximab from consideration for FDA approval (though also approved in the EU).  The company also markets a biosimilar infliximab in the EU.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Ziextenzo is the third pegfilgrastim biosimilar to be approved by the FDA. The product entered the marketplace in November 2019 at a wholesale price slightly below that for competitors Udenyca and Fulphila (37% WAC discount to Neulasta vs. 33% for its competitors).

Company name

Product name

Brand name

Stage of development

Approved

 

 

 

Sandoz

LA-EP2006

Ziextenzo

Application filed December 2015; complete response letter issued June/July 2016; resubmitted application April 2, 2019. FDA approved November 2019

Mylan/Biocon

MYL-1401H

Fulphila

Application filed in February 2017. FDA approved June 2018; launched July 2018

In Development

 

 

Kashiv Biosciences                             

TPI-120

 TBD

Application possible in 2020

Apotex

 N/A

Lapelga

Submitted December 2014. No FDA action reported (complete response letter issued?)

Sandoz Sets Ziextenzo Price 37% Below WAC for Reference Neulasta

(November 15, 2019) According to reports, Sandoz has set a price of $3,925 for a 6- mg dose of its new pegfilgrastim biosimilar Ziextenzo™. Based on this pricing, the third biosimilar pegfilgrastim will undercut the wholesale acquisition cost (WAC) of Neulasta® by 37%.

More Positive News From Coherus

(November 6, 2019) Coherus Biosciences announced that its marketshare for its lead biosimilar product Udenyca® had reached 19% as of end of the third quarter. The company is hoping to crack 20% by the end of 2019.

Sandoz Gets FDA Approval for Its Pegfilgrastim Biosimilar, Ziextenzo

(November 5, 2019) Sandoz received its long-awaited nod to begin marketing Ziextenzo, the third pegfilgrastim biosimilar. Approved and marketed in Europe in 2018, pegfilgrastim-bmez should be available for prescription by doctors before the end of 2019, according to Sandoz.

Sandoz Resubmits Its Pegfilgrastim Biosimilar Application

(April 3, 2019) Sandoz may be chomping at the bit to market its long-delayed pegfilgrastim biosimilar. First rejected by the Food and Drug Administration (FDA) in 2016, the manufacturer of Zarxio® (filgrastim) has completed its 351(k) biosimilar resubmission for its pegylated filgrastim agent.

A Conversation With Doug Long, IQVIA

(February 21, 2019) Doug Long, Vice President of Industry Relations at IQVIA (formerly QuintilesIMS), spoke with us about some of the intracacies of the filgrastim and pegfilgrastim marketplace, and regarding improving access to biosimilars in general.

More Details on Coherus Bioscience’s Udenyca Launch

(January 8, 2019) At the JP Morgan Investor Conference yesterday in San Francisco, Coherus President Dennis Lanfear outlined what he considers a “full-on branded launch” for the biosimilar maker’s key product.

Biosimilar Maker Adello Biologics Bought by Pharma Research Company

(January 4, 2019) The assets of biosimilar drug developer Adello Biologics were sold to Kashiv Pharma, LLC, the companies announced on January 4, 2019. The new company will now be known as Kashiv Biosciences, with its headquarters in Bridgewater, New Jersey.

Coherus Gets FDA Approval for Its Pegfilgrastim Biosimilar

(November 2, 2018)  With the Food and Drug Administration (FDA) approval today of Coherus Bioscience’s Udenyca™ (pegfilgrastim-cbqv), the second pegfilgrastim to compete with Amgen’s Neulasta®, much attention will be now focused on the company’s November 8 earning call.

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. In addition to granting marketing authorization to Coherus Biosciences for its pegfilgrastim biosimilar, it has also approved the marketing of Pelgraz®, a pegfilgrastim produced by Accord Healthcare.

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.

Mylan’s Fulphila Pegfilgrastim Biosimilar Launches at Big Discount

(July 30, 2018) The first pegfilgrastim biosimilar (Fulphila™) in the US has begun marketing, and Mylan/Biocon are offering a 33% discount to the wholesale acquisition cost (WAC) of the originator product Neulasta®.

What Is the Biosimilar Pegfilgrastim Market Opportunity?

(May 25, 2018) This means a US market of approximately $4 billion for one year of sales. Amgen also noted that 62% of its first-quarter Neulasta sales are associated with its Onpro® kit.

Coherus Biosciences Reaffirms Its Pegfilgrastim Biosimilar Hopes

(May 11, 2018) On a quarterly investor call on May 10, Chief Executive Officer Denny Lanfear also related that an approval decision from the European Medicines Agency (EMA) on this product is expected by June 28, 2018.

Sandoz receives EU approval for Erelzi (biosimilar etanercept)

(June 30, 2017) The European Commission (EC) has approved Sandoz’ (a Novartisdivision) Erelzi (biosimilar etanercept) for use in Europe, to treat multiple inflammatory diseases. Erelzi is approved for use in all indications of the reference medicine, Enbrel.

Coherus Readying to Resubmit Its Pegfilgrastim Application

(January 27, 2017) News about Coherus Biosciences has been limited since the Food and Drug Administration (FDA) rejected its initial application for a pegfilgrastim biosimilar last June. However, at this year’s JP Morgan Healthcare Conference in San Francisco, Coherus issued some positive signs of progress.

The FDA Rejects Mylan/Biocon’s Pegfilgrastim; Market Still Awaits a Biosimilar for Neulasta

(October 11, 2017) In the latest blow to those seeking an alternative to Amgen’s Neulasta®, the Food and Drug Administration (FDA) sent a complete response letter to Biocon, citing manufacturing plant deficiencies, in its rejection of their biosimilar pegfilgrastim application.

Pegfilgrastim: 0 for 3 on Biosimilars at FDA

(June 13, 2017) On June 12, Coherus Biosciences received word of the Food and Drug Administration’s (FDA’s) rejection of its biosimilar pegfilgrastim. Manufacturers have now taken 3 swings and misses, striking out in their quest for a biosimilar version of another blockbuster product.

A Nurse's View of Neutropenia

Neutropenic Fever: A Sign of Serious Infection

Clinical Trials of Ziextenzo

Published Trial Results

In addition to its supporting data on physiochemical and structural characteristics, Sandoz’s biologic licensing application was supported by two phase 3 clinical trials, which are described here.

In the PROTECT-1 study, researchers from Brazil, Mexico, Ukraine, Russia, and India evaluated the use of LA-EP2006 compared with the reference agent Neulasta in 218 women with breast cancer who received myelosuppressive chemotherapy. For this randomized, double-blind trial, 157 women (≥ 18 yr) were given the biosimilar G-CSF and 159 women were administered the reference product for ≤ 6 cycles. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with absolute neutrophil count <0.5 × 109 per liter). Equivalence was defined by 90% and 95% confidence intervals being within a 1 day margin.  The researchers revealed a minimal difference in mean DSN (mean difference, 0.07 days), and no safety profile differences between the two drugs. On the basis of these results, they concluded that LA-EP2006 was not inferior to Neulasta in patients with breast cancer receiving myelosuppressive chemotherapy.

In the PROTECT-2 trial, multinational investigators (including the US) studied 308 women with early-stage breast cancer who were receiving highly myelosuppressive chemotherapy for six or more cycles. The study drugs were given on day 2 of each cycle.

The primary endpoint was DSN during the first cycle. One hundred fifty five were administered LA-EP2006 and 153 were given Neulasta.

The mean DSN was equivalent between the two groups (1.36 days vs. 1.19 days, NS) in cycle 1. The researchers found no clinically significant differences in secondary efficacy parameters, safety profiles, or the presence of neutralizing antibodies between the study groups and throughout each cycle of chemotherapy. They concluded that LA-EP2006 was therapeutically equivalent to Neulasta in the prevention of neutropenia in patients with early-stage breast cancer.

 Finally, a pooled analysis of the two phase 3 studies was performed. The primary end point, mean DSN in the first chemotherapy cycle was similar in both the LA-EP2006 and reference groups (1.05 days vs. 1.01 days, respectively), The nadir of absolute neutrophil count and the incidence of febrile neutropenia were also determined to be similar between LA-EP2006 and reference pegfilgrastim, as were the safety and tolerability profiles.

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