Last update: 19 May 2023
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).
Last update: 19 May 2023
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.
Zarxio (filgrastim-sndz) was the first product approved in the US as a biosimilar in 2015 [1].
To date, FDA has approved 40 biosimilars within the product classes of: 1) insulin; 2) granulocyte colony-stimulating factor; 3) monoclonal antibodies and 4) tumour necrosis factor-alpha (TNF-α), see Table 1.
Table 1: FDA approved biosimilars* | ||||
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 |
Alymsys (bevacizumab-maly) | bevacizumab |
NSCLC Cervical cancer Colorectal cancer Glioblastoma Ovarian, fallopian tube or primary peritoneal cancer Renal cell carcinoma |
13 Apr 2022 | Amneal Pharmaceuticals |
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 |
Byooviz | ranibizumab |
Macular oedema Macular oedema following RVO mCNV Wet AMD |
17 Sep 2021 | Samsung Bioepis |
Cimerli (ranibizumab-eqrn) | ranibizumab |
Diabetic macular oedema Diabetic retinopathy Macular oedema following RVO mCNV Wet AMD |
2 Aug 2022§ | Coherus Biosciences |
Cyltezo (adalimumab-adbm) | adalimumab |
Ankylosing spondylitis Crohn’s disease Juvenile arthritis Psoriatic arthritis Psoriasis Rheumatoid arthritis Ulcerative colitis |
25 Aug 2017 15 Oct 2021§ |
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 |
Fylnetra (pegfilgrastim-pbbk) | pegfilgrastim | Febrile neutropenia | 26 May 2022 | Kashiv Biosciences (Amneal Pharmaceuticals) |
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 |
Idacio (adalimumab-aacf) | adalimumab |
Ankylosing spondylitis Crohn’s disease Juvenile idiopathic arthritis Plaque psoriasis Psoriatic arthritis Psoriasis Rheumatoid arthritis Ulcerative colitis |
14 Dec 2022 | Fresenius Kabi |
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) |
Releuko (filgrastim-ayow) | filgrastim | Febrile neutropenia | 25 Feb 2022 | Kashiv Biosciences (Amneal Pharmaceuticals) |
Rezvoglar (insulin glargine-aglr) | insulin glargine | Diabetes | 17 Dec 2021 | Eli Lilly |
Riabni (rituximab-arrx) |
rituximab |
Chronic lymphocytic leukemia Rheumatoid arthritis Granulomatosis with polyangiitis Non-Hodgkin lymphoma |
17 Dec 2020 | Amgen |
Ruxience (rituximab-pvvr) | rituximab |
Chronic lymphocytic leukemia Granulomatosis with polyangiitis Non-Hodgkin lymphoma |
23 Jul 2019 | Pfizer |
Semglee (insulin glargine-yfgn) | insulin glargine | Diabetes |
11 Jun 2020 28 Jul 2021§ |
Biocon/Viatris (formerly Mylan) |
Stimufend (pegfilgrastim-fpgk) | pegfilgratim | Supportive care medicine for patients with non-myeloid cancer | 6 Sep 2022 | Fresenius Kabi |
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 |
Vegzelma (bevacizumab-adcd) | bevacizumab |
Glioblastoma Metastatic breast cancer Metastatic colorectal cancer Non-small cell lung cancer |
27 Sep 2022 | Celltrion |
Yusimry (adalimumab-aqvh) | adalimumab |
Ankylosing spondylitis Crohn’s disease Juvenile arthritis Psoriatic arthritis Psoriasis Rheumatoid arthritis Ulcerative colitis |
17 Dec 2021 | 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 |
Breast neoplasms Colorectal neoplasms NSCLC Ovarian neoplasms Renal cell carcinoma |
27 Jun 2019 | Pfizer |
*Data updated 19 May 2023 §Date approved as an interchangeable biosimilar. Semglee was approved as the first interchangeable biosimilar in the US on 28 July 2021 [5]. AMD: age-related macular degeneration; FDA: US Food and Drug Administration; mCNV: myopic choroidal neovascularization; NSCLC: non-small-cell lung carcinoma; ODAC: Oncologic Drugs Advisory Committee; RVO: retinal vein occlusion. |
FDA has approved six follow-on biologicals in the product classes of enoxaparin sodium (Enoxaparin sodium and M-Enoxaparin); insulin (Admelog, Basaglar and Lusduna) and teriparatide (PF708), for use in the US, see Table 2. The approval for one insulin glargine (Lusduna) and teriparatide follow-on biological (PF708) are tentative pending patent litigation.
Table 2: FDA approved follow-on biologicals* | ||||
Product name | Active substance | Therapeutic area | Authorization date | Manufacturer/ Company name |
Admelog# | insulin lispro | Diabetes | 11 Dec 2017 | Sanofi |
Basaglar# | insulin glargine | Diabetes | 16 Dec 2015 |
Eli Lilly/ Boehringer Ingelheim |
Enoxaparin sodium§ | Enoxaparin sodium | Prophylaxis of Deep Vein Thrombosis | 14 Mar 2019 | Amphastar Pharms |
M-Enoxaparin§ | Enoxaparin sodium | Prophylaxis of Deep Vein Thrombosis | 23 Jul 2010 | Momenta/Sandoz, India/Germany |
Lusduna# (tentative approval) | insulin glargine | Diabetes | 20 Jul 2017 | Merck Sharpe & Dohme |
PF708# (tentative approval) | teriparatide | Osteoporosis | 7 Oct 2019 | Pfenex |
*Data updated 19 May 2023 #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. §Product not approved under the 351k legislation in the US |
Two somatropins – Omnitrope (Sandoz) and Valtropin (LG Life Sciences, Biopartners) – have been approved by FDA in 2007 as a follow-on protein product. Omnitrope is being marketed in the US since 2007 for GHD in children and adults.
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 [2]. 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 [3].
Most of 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 [4].
The FDA made a landmark decision on 28 July 2021 to approve the insulin glargine biosimilar Semglee (insulin glargine-yfgn) as the first interchangeable biosimilar product approved in the US for the treatment of diabetes [5].
Related articles
Biosimilars approved in Europe
References
1. 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
2. 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
3. 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
4. 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
5. GaBI Online - Generics and Biosimilars Initiative. FDA approves first interchangeable insulin glargine biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Jul 1]. Available from: www.gabionline.net/Guidelines/FDA-issues-final-guidance-on-naming-biologicals
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Source: US FDA
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.
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Best regards, Louis.
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.
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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