Product Profile: Udenyca

Product Profile:

Pegfilgrastim-cbqv (Udenyca)

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 Coherus Biosciences

Summary: Udenyca (CHS-1701) is a biosimilar version of pegfilgrastim (reference product, Neulasta by Amgen) that is manufactured by Coherus Biosciences. A biologic license application for approval via the 351(k) biosimilar pathway was originally submitted to the Food and Drug Administration (FDA) in August 2016, with final approval given in November 2018.  This was one of the first biosimilar agents approved by the FDA based on its physiochemical and structural evidence but on phase 1 clinical trial data only. The biosimilar will be launched on January 3, 2019, according to Coherus, at an initial wholesale acquisition cost discount of 33% to Neulasta.

About the Manufacturer

Coherus Biosciences is a “pure-play” biosimilar manufacturer; that is, it is not developing or marketing any nonbiosimilar products. Founded in 2010, Coherus Biosciences has several biosimilars in its pipeline: adalimumab, etanercept, ranibizumab, and aflibercept are either in late-stage or early-stage development. The company’s sole approved product, a biosimilar of pegfilgrastim, is also approved in the EU. Coherus is seeking a marketing partner for commercializing this biosimilar outside of the US.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Udenyca is the second pegfilgrastim biosimilar to be approved by the FDA. The product will enter the marketplace in January 2019 at a wholesale price equal to that for Mylan’s Fulphila.

Company name

Product name

Brand name

Stage of development

Approved

 

 

 

Mylan/Biocon

MYL-1401H

Fulphila

Application filed in February 2017. FDA approved June 2018; launched at 33% discount off of WAC of Neulasta (6% discount from ASP)

In Development

 

 

Adello                             

TPI-120

 TBD

Application possible in 2018

Apotex

 N/A

Lapelga

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

Sandoz

LA-EP2006

 TBD

Submitted December 2015; Complete response letter issued, June/July 2016; withdrew EMA application January 2017; new application possible 2019

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 Udenyca

Published Trial Results

In addition to its supporting data on physiochemical and structural characteristics, Coherus’ biologic licensing application was supported by phase 1 clinical data only (in healthy subjects, not patients). Three phase 1 trials were conducted, two are described here.

The objectives of this phase 1 trial, published in abstract form only, in healthy volunteers, was to compare the pharmacokinetics (PK), pharmacodynamics (PD), and safety of CHS-1701 with the reference pegfilgrastim product Neulasta (manufactured by Amgen).

In this trial, a single-blind, randomized, crossover study, 122 healthy volunteers were randomized to one of three treatment periods: a 6-mg dose of CHS-1701 and two 6-mg doses of Neulasta. Each treatment period was separated by a washout period of at least 28 days.

Bioequivalence was demonstrated if the 90% confidence interval (CI) for the geometric mean ratio (GMR) of CHS-1701 to pegfilgrastim was within 80-125% for primary endpoints: area under the plasma concentration–time curve from 0 to infinity (AUC0-∞) and maximum concentration (Cmax) for pharmacokinetics (PK) and maximum absolute neutrophil count (ANCmax) and ANC area under the curve (ANC AUCs) in terms of pharmacodynamics (PD). Baseline characteristics were comparable between treatment groups (median age, 29.5 yr; age range, 18–45 yr).

The researchers reported that PK bioequivalence criteria were met for Cmax (GMR = 105.0; 90% CI, 95.5–115.4) and AUC0–∞ (GMR = 97.5; 90% CI, 88.6–107.2). PD bioequivalence criteria were met for ANCmax (GMR = 99.6; 90% CI, 96.2–103.2), ANC AUC0–last (GMR = 96.7; 90% CI: 92.2, 101.4), and ANC AUC0–480 (GMR = 99.8; 90% CI, 97.7–102.0). Adverse events were reported in 76.0%, 76.6%, and 73.1% of subjects during the CHS-1701, first pegfilgrastim, and second pegfilgrastim dosing periods across treatment sequences, respectively. Treatment-related AEs occurred in 71.9%, 71.2%, and 62.8% of subjects, respectively. The most common included back pain (33.3%–47.9%) and headache (33.3%–41.4%). There were no serious AEs related to the treatment. No differences in AEs among groups were considered statistically significant.

This study demonstrated the bioequivalence of the biosimilar agent to Neulasta. There were no unexpected safety findings, and the two treatments displayed similar safety profiles.

Another trial (unpublished) was conducted in a randomized, double-blind fashion and included a crossover period. All 116 subjects received one 6-mg subcutaneous injection of CHS-1701 or Neulasta. They were randomized to one of two treatment sequences: Neulasta in the first period and CHS-1701 in the second period, or vice versa.

The study results were not published for this investigation. According to Coherus, the study met its primary PD endpoint of absolute neutrophil count (ANC). In terms of PK parameters, the study also met the criteria for bioequivalence for maximum plasma concentration. Interestingly, the PK profile in the period 1 Neulasta group was low (below that of previous studies), which complicated the comparison for the area under the plasma concentration–time curve (AUC).

The safety profiles of the biosimilar and reference product were determined to be equivalent, and none of the healthy volunteers were found to have neutralizing drug antibodies.

Coherus carried out a separate phase I trial of 207 healthy participants that utilized a triple crossover design. The Figures demonstrate that CHS-1701 (Udenyca) was found to be comparable with Neulasta in terms of PD and PK.

Another phase 1 study was undertaken and completed in 2015 to compare the immunogenicity of its biosimilar with that of the reference product. The results of this investigation are unpublished.

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