How the U.S. Compares to Europe on Biosimilar Approvals and Products In the Pipeline Updated March 14, 2022

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  • FDA and EMA both approve additional biosimilar versions of Humira® (adalimumab).
  • FDA also approves its third biosimilar version of Neupogen® (filgrastim).
  • EMA has not approved any new biosimilars in 2022, but has recommended approval of teriparatide biosimilar Sondelbay and the pegfilgrastim biosimilar Stimufend.

As pharmaceutical drug costs attract increasing media attention and political scrutiny, a growing number of biosimilar drugs are set to enter the U.S. and European markets in the coming years. Global sales for the top ten branded biologic drugs totaled approximately $85 billion in 2020[1]. In a September 2020 report, the IQVIA Institute for Human Data Science estimated biosimilar sales totaling $80 billion over the next five years compared to $14 billion during the previous five years (2015-2019), and that the availability and use of biosimilar medicines would reduce U.S. drug costs by $100 billion through 2024. In a January 2022 report, IQVIA updated global estimates showing estimated biosimilar sales of about $40 billion in 2025 and $75 billion in 2030.

In the FDA’s Center for Drug Evaluation and Research’s (CDER) annual report, the FDA highlighted the three biosimilar approvals in 2020 under the Biologics Price Competition and Innovation Act (BPCIA) of 2009, which was “designed to create competition, increase patient access, and potentially reduce cost of important therapies.” The FDA’s Biosimilars Action Plan, unveiled in 2018, has been designed to aid the development of a market for biosimilars in order to increase competition for biologic drugs, which make up 40% of U.S. pharmaceutical spending. Competition in the heavily regulated marketplace for these blockbuster therapeutics is expected to substantially impact the pharmaceutical industry and national health systems. To date, the U.S. has considerably lagged behind Europe’s expansion of biosimilar drug options.

Since 2005, the biosimilar regulatory framework in Europe has been implemented through the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA). The CHMP provides initial assessments for marketing authorization of new medicines that are ultimately approved centrally by the EMA. Since Sandoz’s somatotropin biosimilar, Omnitrope®, was first authorized on April 12, 2006, an additional 83 applications have been approved in Europe. Fourteen of the authorizations have been withdrawn post-approval (Table 1).

The U.S. did not implement a regulatory framework for biosimilar evaluation until after enactment of the Biologics Price Competition and Innovation Act (BPCIA) of 2009. Given that the first U.S. biosimilar drug was approved almost a decade after the first in Europe, the number of authorized biosimilar drugs in Europe far exceeds the number of biosimilars approved in the United States. Sandoz’s filgrastim biosimilar, Zarxio®, received the first U.S. approval in 2015, whereas nine filgrastim biosimilars have been approved in Europe dating back to multiple authorizations in 2008. Zarxio® (in the U.S.) and Zarzio® (in Europe) are biosimilar to the reference product Neupogen® marketed by Amgen and originally licensed in 1991. Subsequent to Zarxio®’s approval, 33 other biosimilar drugs have gained U.S. approval to date including two interchangeable products (Table 2)

As illustrated in the following graph, while the EU’s significant head start led to an imbalance in the number of biosimilar drugs available in the respective markets, the EU’s relatively higher rate of approvals in recent years has widened its lead over the United States, although the U.S. FDA reversed that trend in 2019 with ten approvals. Through 2021 and thus far in 2022, relatively fewer biosimilars have been approved by both FDA and EMA than in prior years. Given the increasing competition between biosimilar manufacturers in Europe, four EMA-authorized biosimilar products were withdrawn in 2021.

A recent study of U.S. biosimilar approvals found that most comparative efficacy trials conducted to obtain FDA approval for a biosimilar had a tendency to be larger, longer, and more costly than clinical trials required for originator products. Moreover, the FDA requires animal studies whereas the EMA does not require animal studies to approve a biologic product. Further, given the difficult patent litigation and competitive landscapes, there appear to be fewer biosimilar BLAs than in 2017-2019, and launches of FDA-approved adalimumab and rituximab biosimilars are delayed due to settlements of patent litigations. Thus, in addition to the patent litigation landscape, there are regulatory hurdles and costs faced by biosimilar applicants that deter or delay biosimilar products from reaching the U.S. market.

Currently, fourteen biosimilar applications are under review by the EMA for marketing authorization (Table 3). As an increasing number of patents expire on blockbuster biologic drugs, the number of abbreviated biologics license applications is also increasing. Biosimilars for more than 28 different original biologics are currently navigating biosimilar pathways or are in late stage development in the U.S. (Table 4).

On December 20, 2021, the FDA approved Coherus’ adalimumab YusimryTM biosimilar. “YUSIMRY represents an enormous commercial opportunity for Coherus as we continue our mission of increasing patient access to important biologic medicines while at the same time lowering the cost of care,” said Paul Reider, Chief Commercial Officer of Coherus. “Humira is the top-selling drug in the U.S. with 2020 net sales exceeding $16 billion, and demand is high across the healthcare ecosystem for a less expensive Humira biosimilar. We will deliver a compelling value proposition to all stakeholders and look forward to launching YUSIMRY in 2023.” On February 28, 2022, the FDA approved Amneal and Kashiv’s filgrastim ReleukoTM biosimilar. “The U.S. approval of our first biosimilar is a very significant milestone for Amneal. Biosimilars represent the next wave of providing access to affordable medicines in the U.S. We are building a global biosimilars business by leveraging partner assets to start and then leveraging our own key capabilities over time. Our goal is to become a meaningful long-term player in biosimilars,” said Chirag and Chintu Patel, Co-Chief Executive Officers.

Table 1. European Medicines Agency List of Approved Biosimilar Drugs (updated March 13, 2022).

Biosimilar Proprietary Name

Drug

Product

Owner Status Authorization Date
Abasaglar
(previously Abasria)
Insulin Glargine Eli Lilly Regional
Operations GmbH
Authorized 9/9/2014
Abevmy Bevacizumab Mylan IRE Healthcare Limited Authorized 4/21/2021
Abseamed Epoetin Alfa Medice Arzneimittel Pütter GmbH & Co. Kg Authorized 8/28/2007
Accofil Filgrastim Accord Healthcare Ltd Authorized 9/18/2014
Admelog Insulin lispro Sanofi Authorized 5/19/2017
Alpheon Recombinant Human
Interferon Alfa-2a
Biopartners GmbH Refused
Alymsys Bevacizumab Mabxience Research SL Authorized 3/26/2021
Amgevita Adalimumab Amgen Europe Authorized 3/22/2017
Amsparity Adalimumab Pfizer Europe MA EEIG Authorized 2/13/2020
Aybintio Bevacizumab Samsung Bioepis NL B.V. Authorized 8/20/2020
Bemfola Follitropin Alfa Gedeon Richter Plc. Authorized 3/27/2014
Benepali Etanercept Samsung Bioepis
Uk Limited (Sbuk)
Authorized 1/14/2016
Binocrit Epoetin Alfa Sandoz GmbH Authorized 8/28/2007
Biograstim Filgrastim Abz-Pharma GmbH Withdrawn 9/15/2008
Blitzima Rituximab Celltrion Authorized 7/13/2017
Byooviz Ranibizumab Samsung Bioepis Authorized 8/18/2021
Cyltezo Adalimumab Boehringer Ingelheim International GmbH

Authorized

Withdrawn

11/10/2017

1/15/2019

Epoetin Alfa Hexal Epoetin Alfa Hexal Ag Authorized 8/28/2007
Equidacent Bevacizumab Centus Biotherapeutics Europe Limited

Authorized

Withdrawn

9/25/2020

10/11/2021

Erelzi Etanercept Sandoz GmbH Authorized 6/23/2017
Filgrastim Hexal Filgrastim Hexal Ag Authorized 6/2/2009
Filgrastim ratiopharm Filgrastim Ratiopharm GmbH Withdrawn 9/15/2008
Flixabi Infliximab Samsung Bioepis
Uk Limited (SBUK)
Authorized 5/26/2016
Fulphila Pegfilgrastim Mylan S.A.S. Authorized 11/20/2018
Grastofil Filgrastim Apotex Europe Bv Authorized 10/18/2013
Grasustek Pegfilgrastim Juta Pharma GmbH Authorized 4/26/2019
Halimatoz Adalimumab Sandoz GmbH

Authorized

Withdrawn

7/26/2018

12/18/2020

Hefiya Adalimumab Sandoz GmbH Authorized 7/26/2018
Herzuma Trastuzumab Celltrion Healthcare Hungary Kft. Authorized 2/9/2018
Hukyndra Adalimumab Stada Arzneimittel AG Authorized 11/15/2021
Hulio Adalimumab Mylan S.A.S. Authorized 9/19/2018
Hyrimoz Adalimumab Sandoz GmbH Authorized 7/26/2018
Idacio Adalimumab Fresenius Kabi Deutschland GmbH Authorized 4/2/2019
Imraldi Adalimumab Samsung Bioepis UK Limited (SBUK) Authorized 8/24/2017
Inflectra Infliximab Hospira Uk Limited Authorized 9/10/2013
Inhixa Enoxaparin Sodium Techdow Europe Ab Authorized 9/15/2016
Insulin aspart Sanofi Insulin aspartate Sanofi-Aventis groupe Authorized 7/26/2020
Kanjinti Trastuzumab Amgen/Allergan Authorized 5/16/2018
Kirsty (previously Kixelle) Insulin aspart Mylan Authorized 2/8/2021
Kromeya Adalimumab Fresenius Kabi Deutschland GmbH

Authorized

Withdrawn

4/2/2019

12/17/2019

Lextemy Bevacizumab Mylan IRE Healthcare Limited

Authorized

Withdrawn

4/21/2021

6/21/2021

Libmyris Adalimumab Stada Arzneimittel AG Authorized 11/12/2021
Livogiva Teriparatide Theramex Ireland Limited Authorized 8/27/2020
Lusduna Insulin Glargine Merck Sharp &
Dohme Limited

Authorized

Withdrawn

4/1/2017

10/29/2018

Lyumjev Insulin lispro Eli Lilly Nederland B.V. Authorized 3/24/2020
Movymia Teriparatide Stada Arzneimittel Ag Authorized 1/11/2017
Mvasi Bevacizumab Amgen Europe B.V. Authorized 1/15/2018
Nepexto Etanercept Mylan and Lupin Authorized 6/4/2020
Nivestim Filgrastim Hospira Uk Ltd Authorized 6/8/2010
Nyvepria Pegfilgrastim Pfizer Europe MA EEIG Authorized 11/19/2020
Ogivri Trastuzumab Viatris Authorized 12/12/2018
Omnitrope Somatropin Sandoz GmbH Authorized 4/12/2006
Onbevzi Bevacizumab Samsung Bioepis Co., Ltd. Authorized 1/13/2021
Ontruzant Trastuzumab Samsung Bioepis Co., Ltd. Authorized 11/17/2017
Ovaleap Follitropin Alfa Teva Pharma B.V. Authorized 9/27/2013
Oyavas Bevacizumab STADA Arzneimittel AG Authorized 3/26/2021
Pegfilgrastim Mundipharma (Cegfila) Pegfilgrastim Mundipharma Biologics S.L. Authorized 12/19/2019
Pelgraz Pegfilgrastim Accord Healthcare Limited Authorized 9/25/2018
Pelmeg Pegfilgrastim Cinfa Biotech S.L. Authorized 11/20/2018
Qutavina Teriparatide EuroGenerics Holdings BV

Authorized

Withdrawn

8/31/2020

11/26/2020

Ratiograstim Filgrastim Ratiopharm GmbH Authorized 9/15/2008
Remsima Infliximab Celltrion Healthcare
Hungary Kft.
Authorized 9/10/2013
Retacrit Epoetin Zeta Hospira Uk Limited Authorized 12/18/2007
Ritemvia Rituximab Celltrion

Authorized

Withdrawn

7/13/2017

6/21/2021

Rituzena (previously Tuxella) Rituximab Celltrion

Authorized

Withdrawn

7/13/2017

April 12, 2019

Rixathon Rituximab Sandoz GmbH Authorized 6/15/2017
Riximyo Rituximab Sandoz GmbH Authorized 6/15/2017
Ruxience Rituximab Pfizer Europe MA EEIG Authorized 4/1/2020
Semglee Insulin glargine Mylan S.A.S. Authorized 3/27/2018
Silapo Epoetin Zeta Stada Arzneimittel Ag Authorized 12/18/2007
Solumarv Insulin Human Marvel Lifesciences Ltd Refused
Solymbic Adalimumab Amgen Europe

Authorized

Withdrawn

3/22/2017

6/15/2018

Terrosa Teriparatide Gedeon Richter Plc. Authorized 1/4/2017
Tevagrastim Filgrastim Teva GmbH Authorized 9/15/2008
Thorinane Enoxaparin Sodium Pharmathen S.A. Authorized 9/15/2016
Trazimera Trastuzumab Pfizer Authorized 7/26/2018
Truxima Rituximab Celltrion Healthcare
Hungary Kft.
Authorized 2/17/2017
Udenyca Pegfilgrastim Coherus/ERA Consulting GmbH

Authorized

Withdrawn

9/25/2018

2/4/2021

Yuflyma Adalimumab Celltrion Healthcare
Hungary Kft.
Authorized 2/11/2021
Valtropin Somatropin Biopartners GmbH Withdrawn 4/24/2006
Zarzio Filgrastim Sandoz GmbH Authorized 2/6/2009
Zercepac Trastuzumab Accord Healthcare S.L.U. Authorized 7/28/2020
Zessly Infliximab Sandoz GmbH Authorized 5/18/2018
Ziextenzo Pegfilgrastim Sandoz GmbH Authorized 11/22/2018
Zirabev Bevacizumab Pfizer Authorized 2/14/2019

Table 2. U.S. Food and Drug Administration List of Approved Biosimilar Drugs.

No. Drug Product Company Reference Product and Sponsor Marketing Status FDA Approval Date
34

Releuko

(filgrastim-ayow)

Kashiv Biosciences & Amneal Pharmaceuticals

Amgen

Neupogen®

Not Available 2/28/2022
33 YusimryTM (adalimumab-aqvh) Coherus

AbbVie

Humira®

Not Available

12/20/2021
32

RezvoglarTM

(insulin glargine-aglr)

Eli Lilly

Sanofi

Lantus®

Not Available

12/20/2021
31

ByoovizTM

(ranibizumab-nuna)

Samsung Bioepis and Biogen

Genentech

Lucentis®

Not Available

Launch Delayed to June 2022

9/17/2021
30

SemgleeTM

(insulin glargine-yfqn)

INTERCHANGEABLE

Viatris and Biocon Biologics

Sanofi

Lantus®

Launched

November 2021

7/28/2021
29

RiabniTM

(rituximab-arrx)

Amgen Biogen and Genentech Rituxan®

Launched

January 2021

12/17/2020
28

HulioTM

(adalimumab-fkjp)

Mylan

AbbVie

Humira®

Not available

Launch Delayed to 2023

7/6/2020
27 NyvepriaTM (pegfilgrastim-apgf) Pfizer

Amgen

Neulasta®

Launched

January 2021

6/10/2020
26

AvsolaTM

(infliximab-axxq)

Amgen

Janssen

Remicade®

Launched

July 2020

12/6/2019
25

AbriladaTM

(adalimumab-afzb)

Pfizer

AbbVie

Humira®

Not available

Launch Delayed to 2023

11/15/2019
24

ZiextenzoTM

(pegfilgrastim-bmez)

Sandoz

Amgen

Neulasta®

Launched November 2019 11/4/2019
23 HadlimaTM (adalimumab-bwwd) Samsung Bioepis

AbbVie

Humira®

Not available

Launch Delayed to 2023

7/23/2019
22 RuxienceTM (rituximab-pvvr) Pfizer Biogen and Genentech Rituxan® Launched January 2020 7/23/2019
21 ZirabevTM (bevacizumab-bvzr) Pfizer

Genentech/Roche

Avastin®

Launched December 2019 6/28/2019
20 KanjintiTM (trastuzumab-anns) Amgen

Roche/Genentech

Herceptin®

Launched

July 2019

6/13/2019
19

EticovoTM

(etanercept-ykro)

Samsung Bioepis

Amgen

Enbrel®

Not available 4/25/2019
18 TrazimeraTM (trastuzumab-qyyp) Pfizer

Roche/Genentech

Herceptin®

Launched February 2020 3/11/2019
17 Ontruzant™ (trastuzumab-dttb) Samsung Bioepis

Roche/Genentech

Herceptin®

Launched

April 2020

1/18/2019
16 Herzuma™ (trastuzumab-pkrb) Celltrion and Teva

Roche/Genentech

Herceptin®

Launched

March 2020

12/14/2018
15 Truxima™ (rituximab-abbs) Celltrion and Teva Biogen and Genentech Rituxan® Launched November 2019 11/28/2018
14 Udenyca™ (pegfilgrastim-cbqv) Coherus BioSciences

Amgen

Neulasta®

Launched January 2019 11/2/2018
13 Hyrimoz™ (adalimumab-adaz) Sandoz

AbbVie

Humira®

Not available

Launch Delayed to 2023

10/30/2018
12

NivestymTM

(filgrastim-aafi)

Pfizer

Amgen

Neupogen®

Launched October 2018 7/20/2018
11 FulphilaTM (pegfilgrastim-jmdb) Mylan/Biocon

Amgen

Neulasta®

Launched July 2018 6/4/2018
10

Retacrit®

(epoetin alfa-epbx)

Pfizer

Janssen

Procrit®

Launched November 2018 5/15/2018
9

Ixifi®

(infliximab-qbtx)

Pfizer

Janssen

Remicade®

Not Available 12/13/2017
8

Ogivri®

(trastuzumab-dkst)

Mylan/Biocon

Roche/Genentech

Herceptin®

Launched

December 2019

12/01/2017
7 MvasiTM (bevacizumab-awwb)

Amgen

Allergan

Genentech/Roche

Avastin®

Launched

July 2019

9/14/2017
6

CyltezoTM

(adalimumab-adbm)

INTERCHANGEABLE

Boehringer Ingelheim International GmbH

AbbVie

Humira®

Not available

Launch Delayed to July 2023

8/25/2017
5

Renflexis®

(infliximab-abda)

Samsung Bioepis

Janssen

Remicade®

Launched July 2017 4/21/2017
4 Amjevita® (adalimumab-atto) Amgen

AbbVie

Humira®

Not available

Launch Delayed to Jan. 31, 2023

9/23/2016
3

Erelzi ®

(etanercept-szzs)

Sandoz

Amgen

Enbrel®
(etanercept)

Not Available 8/30/2016
2

Inflectra®

(infliximab-dyyb)

Celltrion/Pfizer

Janssen

Remicade®

Launched Nov. 2016 4/05/2016
1

Zarxio®

(filgrastim-sndz)

Sandoz

Amgen

Neupogen®

Launched
Sept. 2015
03/06/2015

Table 3. European Medicines Agency List of Biosimilars Under Evaluation for Marketing Approval (Source: EMA list of applications for new human medicines compiled on March 8, 2022 and published on March 11, 2022).

Drug Product Reference Product Proprietary Name Reference Product Sponsor Number of Applications
Bevacizumab Avastin® Genentech/Roche 2
Eptacog alfa NovoSeven® Novo Nordisk 1
Filgrastim     1
Pegfilgrastim Neulasta® Amgen 2
Ranibizumab Lucentis® Genentech 3
Teriparatide Forteo®/Forsteo® Eli Lilly 2
Trastuzumab Herceptin® Roche/Genentech 3

 

Table 4. Biologics having already expired or nearing primary patent expiry in the U.S. and biologics that have biosimilars in the regulatory pipeline.

Drug Product

Primary U.S.

Patent Expiry

OnabotulinumtoxinA (Botox®) Primary patents long-expired, various use patents pending
Insulin products (various) Primary patents long-expired
Filgrastim (Neupogen®) 2013
Epoetin alfa (Epogen®) 2013
Pegfilgrastim (Neulasta®) 2015
Adalimumab (Humira®) 2016
Rituximab (Rituxan®) 2018
Cetuximab (Erbitux®) 2018
Omalizumab (Xolair®) 2018
Infliximab (Remicade®) 2018
Teriparatide (Forteo®) 2019
Bevacizumab (Avastin®) 2019
Trastuzumab (Herceptin®) 2019
Tocilizumab (Acetmra®) 2019
Abatacept (Orencia®) 2019
Ranibizumab (Lucentis®) 2020
Panitumumab (Vectibix®) 2020
Eculizumab (Soliris®) 2021
Aflibercept (Eylea®) 2023
Denosumab (Prolia® and Xgeva®) 2023
Ustekinumab (Stelara®) 2023
Certolizumab pegol (Cimzia®) 2024
Golimumab (Simponi®) 2024
Darbepoetin alfa (Aranesp®) 2024
Pertuzumab (Perjeta®) 2024
Ipilimumab (Yervoy®) 2025
Natalizumab (Tysabri®) 2027
Etanercept (Enbrel®) 2028

[1] Based on sales reported by respective manufacturers (1. Humira—Abbvie ($20.39B), 2. Keytruda—Merck ($14.38B), 3. Eylea—Aflibercept ($8.36B), 4. Stelara—Johnson & Johnson ($7.94B), 5. Opdivo—Bristol-Myers-Squibb ($7.92B), 6. Enbrel—Pfizer/Amgen ($6.37B), 7. Avastin—Roche ($5.32B), 8. Trulicity—Eli Lilly ($5.07B), 9. Ocrevus—Roche ($4.61B), 10. Rituxan—Roche ($4.52B).

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

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