Product Profile:

Filgrastim-ayow (Releuko)

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;  and reducing 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 Kashiv Biosciences; marketed by Amneal Pharmaceuticals, Inc.

Biosimilar Drug Profile: Releuko is a biosimilar version of filgrastim (reference product, Neupogen, Amgen) manufactured by Kashiv Biosciences and marketed by Amneal Pharmaceuticals, Inc. Reuleuko was originally developed by Adello Biologics (which was acquired by Kashiv). A US biologic license application for approval via the 351(k) biosimilar pathway was submitted to the Food and Drug Administration (FDA) in September 2017 with approval by the FDA in March 2022 (a complete response letter was likely filed by the FDA in the intervening time).  In 2018, Amgen filed a lawsuit claiming patent violations and that Adello failed to follow the necessary biosimilar development protocol outlined by law.

This was the third filgrastim biosimilar approved by the FDA (following Sandoz’s Zarxio® in 2015 and Pfizer’s Nivestym® in 2018). Annual U.S. filgrastim sales in 2021 were $407 million.  with $275 million attributed to the two biosimilars.

About the Manufacturer

Kashiv Biosciences LLC is located in Piscataway, New Jersey. Kashiv Pharma was founded in 2011. Kashiv Pharma purchased Adello Biologics in January 2019 to form Kashiv Biosciences. Amneal Pharmaceuticals acquired a 98% interest in Kashiv’s specialty pharmaceutical division in January 2021. This was the first biosimilar to be approved by the FDA for Kashiv and Amneal.

Amneal also has two other approved biosimilars, a pegfilgrastim biosimilar developed with Kashiv, and a bevacizumab biosimilar developed with mAbxience.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Approved Products


Product Name

Brand Name

Innovator Product

Filing Date

Stage of Development






May 2014

FDA approved March 6, 2015; marketed





Q4 2017 (est)

FDA approved July 20, 2018; marketed






FDA approved August 30, 2012; marketed


Coherus Biosciences




August 2016

Approved November 2, 2018; marketed





February 16, 2017

Approved June 4, 2018; marketed





December 2015/April 2019

FDA Approved November 2019; marketed






FDA approved May 2022

CRL = complete response letter. * Granix was approved under the 505(b)2 pathway, not as a biosimilar.

Filgrastim Products in Development


Product Name

Stage of Development

Tanvex Biologics


FDA issued a CRL September 25, 2019. At that time the FDA did not request additional clinical data or have any safety concerns. The BLA was resubmitted in November 2020. On May 20, 2021 the company communicated that they received a CRL from the FDA.

Partners Amneal and Kashiv Score Approval From FDA for Their Pegfilgrastim Biosimilar

(May 31, 2022) On May 27, Amneal Pharmaceuticals announced that the U.S. Food and Drug Administration granted approval to Fylnetra™ (pegfilgrastim-pbbk), a new biosimilar that will launch later this year.  This is its third biosimilar approval since January 1.

A Profile on Lesser-Known Player in the Biosimilar Space: Amneal Pharmaceuticals

(March 4, 2022) Amneal received FDA approval for its filgrastim biosimilar (Releuko™) on March 1, and it is awaiting decisions on a pegfilgrastim biosimilar and a bevacizumab biosimilar as well.

Tanvex BioPharma Receives Complete Response Letter on Its Filgrastim Biosimilar Application

(June 9, 2021) On May 20, 2021 Tanvex BioPharma, Inc. issued a press release announcing that the FDA has not approved its 351(k) application for TX01, a biosimilar version of filgrastim. In the announcement, Tanvex cited the FDA’s need to complete manufacturing site inspections, which have been altered by COVID-19 pandemic restrictions.

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. 

Biosimilar Maker Adello Bought, Now Kashiv Biosciences

(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.

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 approval 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 Releuko

Clinical Trials of Releuko

The FDA did not require Phase III trials to be conducted in its review for approval. Additionally, no study was required to test equivalence for a clinical end point.

The clinical development program consisted of phase 1, pharmacokinetic (PK) and pharmacodynamic (PD) biosimilarity studies (CL-106 and CL-101) and an immunogenicity study (CL-110). These three studies compared subcutaneous (SC) doses of the biosimilar and US-licensed Neupogen in healthy subjects.

Both PK/PD studies used a single-dose randomized crossover design and used absolute neutrophil count (ANC) as the primary PD endpoint. The immunogenicity study used a two-cycle parallel-arm design in which subjects were given 5 daily doses of drug (biosimilar or Neupogen) during the first cycle and a single dose of the same drug in the second cycle.

Study CL-101

CL-101 was a single-center, randomized, double-blind, single dose, two period crossover study to compare the PK and PD of the biosimilar candidate and US-licensed Neupogen administered as single subcutaneous (SC) injections to two cohorts (2.5 μg/kg [Cohort A] and 5 μg/kg [Cohort B]) comprised of 116 healthy volunteers.

This study did not meet the primary PK endpoint, so an additional trial (CL-106) was conducted.

Study CL-106

This was a randomized (1:1), double-blind, single dose, 2-period crossover study comparing the biosimilar to Neupogen 5 μg/kg, conducted in 58 healthy adults.

The primary objective was to compare PK and PD parameters of the biosimilar and Neupogen after a single 5 μg/kg SC injection. The secondary objective of this study was to compare the safety, tolerability, and immunogenicity of biosimilar and Neupogen, following a single 5 μg/kg SC injection. However, immunogenicity results from this study were not evaluated for drug approval; rather immunogenicity data from study CL-110 were used for the review of the drug for approval.

The geometric mean ratios of the maximum concentration levels, area of the plasma concentration-time curve (0 to infinity) and average neutrophil maximum concentration were within the prespecified limits and determined to demonstrate similarity of the PK and PD endpoints.

Study CL-110

CL-110 was a single-blind, randomized, parallel, multiple-dose, safety, and immunogenicity study. A total of 134 healthy adult subjects were randomized (1:1) to either the biosimilar or reference biologic at a dose of 5 μg/kg daily from Day 1 to Day 5 (Cycle 1), followed by a single dose on Day 1 of Cycle 2 (Study Day 33).

The anti-drug antibodies (ADA) proportion difference fell within the inferiority margins, indicating similarity in immunogenicity.

The three study safety results were pooled to evaluate safety. There were more adverse events in the higher dose arms of the studies, however the safety profiles were similar and there were no clinically meaningful safety difference between the biosimilar and reference product.

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