Biosimilars approved in the US

Biosimilars/General | Posted 14/08/2015 post-comment3 Post your comment

Last update: 5 March 2021

In the US, a legal framework for approving biosimilars was established in 2009, via the Biologics Price Competition and Innovation Act of 2009 (BPCI Act).

FDA V17F30

The BPCI Act is part of the healthcare reform legislation, which was signed into law on 23 March 2010 by President Barack Obama. The BPCI Act establishes an abbreviated approval pathway for biological products that are demonstrated to be ‘highly similar’ (biosimilar) to, or ‘interchangeable’ with, a US Food and Drug Administration (FDA)-licensed biological product.

FDA is still in the process of developing guidelines regarding these types of products and has issued several guidance documents on the subject [1].

Zarxio (filgrastim-sndz) was the first product approved in the US as a biosimilar in 2015 [2]. To date, FDA has approved 29 biosimilars within the product classes of: 1) anti-tumour necrosis factor-alpha (TNF-α); 2) monoclonal antibodies; and 3) granulocyte colony-stimulating factor, plus five follow-on biologicals in the product classes of insulin (Admelog, Basaglar, Lusduna and Semglee) and teriparatide (PF708), for use in the US, see Table 1. The approval for one insulin glargine and teriparatide follow-on biological (PF708) are tentative pending patent litigation.

Table 1: FDA approved biosimilars and follow-on biologicals*
Product name Active substance Therapeutic area Authorization date Manufacturer/ Company name
Abrilada (adalimumab-afzb) adalimumab Ankylosing spondylitis
Crohn’s disease
Juvenile arthritis
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
15 Nov 2019 Pfizer
Admelog# insulin lispro Diabetes 11 Dec 2017 Sanofi
Amjevita (adalimumab-atto) adalimumab Ankylosing spondylitis
Crohn’s disease
Juvenile arthritis
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
23 Sep 2016 Amgen
Avsola (infliximab-axxq) infliximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
6 Dec 2019 Amgen
Basaglar# insulin glargine Diabetes 16 Dec 2015 Eli Lilly/
Boehringer Ingelheim
Cyltezo (adalimumab-adbm) adalimumab Ankylosing spondylitis
Crohn’s disease
Juvenile arthritis
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
25 Aug 2017 Boehringer Ingelheim
Erelzi (etanercept-szzs) etanercept Axial spondyloarthritis
Polyarticular juvenile idiopathic arthritis
Psoriatic arthritis
Plaque psoriasis
Rheumatoid arthritis
30 Aug 2016 Sandoz
Eticovo (etanercept-ykro)  etanercept Axial spondyloarthritis
Polyarticular juvenile idiopathic arthritis
Psoriatic arthritis
Plaque psoriasis
Rheumatoid arthritis
25 Apr 2019 Samsung Bioepis
Fulphila (pegfilgrastim-jmdb) pegfilgrastim Febrile neutropenia  4 Jun 2018 Biocon/Mylan
Hadlima (adalimumab-bwwd) adalimumab Ankylosing spondylitis
Crohn’s disease
Juvenile arthritis
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
23 Jul 2019 Samsung Bioepis
Herzuma (trastuzumab-pkrb) trastuzumab Breast cancer 14 Dec 2018 Celltrion/Teva Pharmaceutical Industries
Hulio (adalimumab-fkjp) adalimumab Ankylosing spondylitis
Crohn’s disease
Juvenile arthritis
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
6 Jul 2020 Mylan
Hyrimoz (adalimumab-adaz) adalimumab Ankylosing spondylitis
Crohn’s disease
Juvenile arthritis
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
30 Oct 2018 Sandoz
Inflectra
(infliximab- dyyb)
infliximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
5 Apr 2016 Pfizer (Hospira)
Ixifi (infliximab-qbtx) infliximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
13 Dec 2017 Pfizer
Kanjinti (trastuzumab-anns)   trastuzumab HER2 breast cancer
HER2 metastatic gastric or gastroesophageal junction adenocarcinoma
13 Jun 2019 Amgen
Lusduna# (tentative approval) insulin glargine Diabetes 22 Jul 2018 Merck Sharpe Dohme
Mvasi (bevacizumab-awwb) bevacizumab NSCLC
Colorectal neoplasms
Renal cell carcinoma
Ovarian neoplasms
Breast neoplasms
14 Sep 2017 Amgen/Allergan
Nivestym (filgrastim-aafi) filgrastim Autologous peripheral blood progenitor cell collection and therapy 
Bone marrow transplantation 
Cancer 
Myeloid leukaemia 
Neutropenia
20 Jul 2018 Pfizer (Hospira)
Nyvepria (pegfilgrastim-apgf) pegfilgrastim Febrile neutropenia 10 Jun 2020 Pfizer (Hospira)
Ogivri (trastuzumab-dkst) trastuzumab HER2 breast cancer
HER2 metastatic gastric or gastroesophageal junction adenocarcinoma
1 Dec 2017 Biocon/Mylan
Ontruzant (trastuzumab-dttb) trastuzumab HER2 breast cancer
HER2 metastatic gastric or gastroesophageal junction adenocarcinoma
18 Jan 2019 Samsung Bioepis/Merck
PF708(tentative approval) teriparatide Osteoporosis 7 Oct 2019 Pfenex
Renflexis (infliximab-abda) infliximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
21 Apr 2017 Samsung Bioepis/Merck
Retacrit (epoetin alfa-epbx) epoetin alfa Anaemia (chronic kidney disease, Zidovudine, chemotherapy)
Reduction of allogeneic red blood cell transfusions
15 May 2018 Pfizer (Hospira)
Riabni
(rituximab-arrx)
rituximab Ankylosing spondylitis
Crohn’s disease
Psoriatic arthritis
Psoriasis
Rheumatoid arthritis
Ulcerative colitis
17 Dec 2020 Amgen
Ruxience (rituximab-pvvr) rituximab Chronic lymphocytic leukemia
Non-Hodgkin lymphoma
Granulomatosis with polyangiitis
23 Jul 2019 Pfizer
Semglee (MYL‑1501D)# insulin glargine Diabetes 11 Jun 2020 Mylan/Biocon
Trazimera (trastuzumab-qyyp) trastuzumab HER2 breast cancer
HER2 metastatic gastric or gastroesophageal junction adenocarcinoma
11 Mar 2019 Pfizer
Truxima (rituximab-abbs) rituximab Non-Hodgkin lymphoma 28 Nov 2018 Celltrion/Teva Pharmaceutical Industries
Udenyca (pegfilgrastim-cbqv) pegfilgrastim Febrile neutropenia  2 Nov 2018 Coherus Biosciences
Zarxio
(filgrastim-sndz)
filgrastim Autologous peripheral blood progenitor cell collection and therapy
Bone marrow transplantation
Cancer
Myeloid leukaemia
Neutropenia
6 Mar 2015 Sandoz
Ziextenzo (pegfilgrastim-bmez)  pegfilgrastim Febrile neutropenia  4 Nov 2019 Sandoz
Zirabev (bevacizumab-bvzr)  bevacizumab NSCLC
Cervical cancer
Colorectal cancer
Renal cell carcinoma
Breast neoplasms
27 June 2019 Pfizer
*Data updated 5 March 2021
#Admelog, Basaglar, Lusduna and PF708 were approved via the FDA’s abbreviated 505(b)(2) pathway as follow-on products not as biosimilars. No insulin lispro or glargine products were licensed under the Public Health Service Act at the time of filing, so there was no ‘reference product’ for a proposed biosimilar product.
FDA: US Food and Drug Administration; NSCLC: Non-Small-Cell Lung Carcinoma; ODAC: Oncologic Drugs Advisory Committee 

The landmark decision by FDA to approve its first biosimilar came in the wake of a unanimous vote two months earlier by FDA advisors who recommended approval of Zarxio [3]. Sandoz, the generics division of Novartis, already markets its biosimilar filgrastim product under the brand name Zarzio in more than 40 countries outside the US [4].

All the products approved so far have been approved as biosimilars, not as interchangeable products. According to the BPCI Act, only a biological that has been approved as interchangeable may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product.

FDA has designated placeholder non-proprietary names that include a 4-digit random suffix, for all of the biosimilars that it has approved to date. The agency issued final guidance on the naming of biologicals in January 2017 [5].

Related articles
Biosimilars approved in Europe

US guidelines for biosimilars

References
1.   GaBI Online - Generics and Biosimilars Initiative. US guidelines for biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Aug 14]. Available from: www.gabionline.net/Guidelines/US-guidelines-for-biosimilars
2.   GaBI Online - Generics and Biosimilars Initiative. FDA approves its first biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Aug 14]. Available from: www.gabionline.net/Biosimilars/News/FDA-approves-its-first-biosimilar
3.   GaBI Online - Generics and Biosimilars Initiative. FDA advisers recommend approval of filgrastim biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Aug 14]. Available from: www.gabionline.net/Biosimilars/News/FDA-advisers-recommend-approval-of-filgrastim-biosimilar
4. GaBI Online - Generics and Biosimilars Initiative. FDA accepts biosimilar filgrastim application [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2015 Aug 14]. Available from: www.gabionline.net/Biosimilars/News/FDA-accepts-biosimilar-filgrastim-application
5.   GaBI Online - Generics and Biosimilars Initiative. FDA issues final guidance on naming biologicals [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2018 Feb 9]. Available from: www.gabionline.net/Guidelines/FDA-issues-final-guidance-on-naming-biologicals 

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Source: US FDA

comment icon Comments (3)
Post your comment
Posted 04/10/2016 by Louis B, GaBI Online Editorial Office
Response to ‘Biosimilars’ posted 18/03/2016

Dear Kauntay Parekh, thank you for your valid and interesting comment on this article. Thank you for sharing your thoughts on this subject. We would be delighted if you would consider submitting a short Commentary paper on this topic to GaBI Journal.
Please feel free to reach us at editorial@gabi-journal.net for further information.

Thank you again and we hope to hear from you soon.
Best regards, Louis.

Posted 18/03/2016 by Kauntay Parekh
Biosimilars

Hi, Hemanth Kumar,

1. How many phase I, II, III trials are needed to be conducted for a Biosimilar in US and EU?
Ans: In US and EU, biosimilar applicant has to discuss with drug regulatory authority to decide the clinical trial (CT) pathway for the particular product (For US FDA and for EU EMA). These regulatory authority devise the CT pathway based on the products similarity with reference biologic (Based on analytical data).
Overall, the more similar the biosimilar product to reference product based on analytical data, the lesser CT will be required.

2. What is the trial duration for these trials (In general)?
Ans: Trial duration varies from product to product but generally these trials get completed within 2-4 years.

3. How the development timelines and trial size differ for biosimilars from their reference biologic drugs?
Ans: Unlike reference product sponsor, biosimilar applicant has to prove similarity, efficacy, safety and toxicity data comparable to reference biologic. Hence, the CT size required for biosimilar is smaller than the reference biologic.

Posted 31/08/2015 by Hemanth Kumar G
Biosimilars

Dear Sir/Madam,
Thank you very much for your articles and news about Biosimilars and generics world at gabionline.
I observed from one of your articles that it takes less than 2 years for completion of Biosimilar pivotal trials, I have a few queries regarding that.
1. How many phase I, II, III trials are needed to be conducted for a Biosimilar in US and EU?
2. What is the trial duration for these trials (In general) ?
3. How the development timelines and trial size differ for Biosimilars from their reference biologic drugs?

I would be grateful if you can answer these queries

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