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Biosimilars approved in the US Posted 14/08/2015

Last update: 31 August 2018

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).

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 12 biosimilars within the product classes of anti-tumour necrosis factor-alpha (TNF-α), HER2/neu and granulocyte colony-stimulating factor, and two follow-on biologicals in the product class of insulin for use in the US, see Table 1. The agency has also granted tentative approval to an insulin glargine follow-on biological, pending patent litigation.

Table 1: FDA approved biosimilars and follow-on biologicals*
Product name	Active substance	Therapeutic area	Authorization date	Manufacturer/ Company name
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
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
Fulphila (pegfilgrastim-jmdb)	pegfilgrastim	Febrile neutropenia	4 Jun 2018	Biocon/Mylan
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
Lusduna# (tentative approval)	insulin glargine	Diabetes	20 Jul 2017	Merck
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)
Ogivri (trastuzumab-dkst)	trastuzumab	HER2 breast cancer HER2 metastatic gastric or gastroesophageal junction adenocarcinoma	1 Dec 2017	Biocon/Mylan
Retacrit (epoetin alfa-epbx)	epoetin alfa	Anaemia (chronic kidney disease, Zidovudine, chemotherapy) Reduction of allogeneic red blood cell transfusions	15 May 2018	Pfizer (Hospira)
Renflexis (infliximab-abda)	infliximab	Ankylosing spondylitis Crohn’s disease Psoriatic arthritis Psoriasis Rheumatoid arthritis Ulcerative colitis	21 Apr 2017	Samsung Bioepis
Zarxio (filgrastim-sndz)	filgrastim	Autologous peripheral blood progenitor cell collection and therapy Bone marrow transplantation Cancer Myeloid leukaemia Neutropenia	6 Mar 2015	Sandoz
*Data updated 31 August 2018 #Admelog, Basaglar and Lusduna 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. NSCLC: Non-Small-Cell Lung Carcinoma.

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 for Amjevita, Cyltezo, Erelzi, Fulphila, Inflectra, Ixifi, Mvasi, Nivestym, Ogivri, Renflexis, Retacrit and Zarxio: adalimumab‑atto, adalimumab‑adbm, etanercept‑szzs, pegfilgrastim-jmdb, infliximab‑dyyb, infliximab-qbtx, bevacizumab-awwb, filgrastim-affi, trastuzumab-dkst, infliximab-abda, epoetin alfa-epbx and filgrastim‑sndz, respectively. 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

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Comments (3)

Response to ‘Biosimilars’ posted 18/03/2016 posted 05/10/2016 - by Louis B, GaBI Online Editorial Office

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.

Biosimilars posted 05/10/2016 - by Kauntay Parekh

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.

Biosimilars posted 02/09/2015 - by Hemanth Kumar G

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