Biobetters: Are They Truly Better?
Main Article Content
Abstract
Biologics have seen an explosion in application for a myriad of diseases. Recently the term “biobetter” has entered the lexicon of the pharmaceutical industry. This marketing term refers to a drug that is supposedly a “better” version of a reference biologic. By this definition, these biologics must invariably have some improved pharmacologic and/or pharmacokinetic parameters, such as a better safety/efficacy profile. In actuality, this is not necessarily the case. Additionally, to-date there is neither a legal nor regulatory pathway in place for the development of said, biobetters. This lack of any classification has led to its inconsistent and often inaccurate use within scientific literature. To rectify this, a framework for the potential correct use of the term biobetter within scientific literature (not regulatory) has been provided. Additionally, an exhaustive reclassification of any drug that have been previously termed “biobetter” has been conducted. We believe this classification system, specifically: true-biobetter, potential-biobetter, or non-biobetter will prevent further misuse of the term in the scientific community without modifying the clinical application of such biological entities in practice and in research.
Keywords:
True-Biobetter, Potential-Biobetter, Non-Biobetter
Article Details
How to Cite
ZAVERI, Rohan Purvin; ASHER, Shreya; PRIEFER, Ronny.
Biobetters: Are They Truly Better?.
Medical Research Archives, [S.l.], v. 10, n. 3, mar. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2715>. Date accessed: 05 nov. 2024.
doi: https://doi.org/10.18103/mra.v10i3.2715.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
[1] U.S. Food and Drug Administration, 2020. Public Workshop: FDA/FTC Workshop 03092020. https://www.fda.gov/drugs/news-events-human-drugs/public-workshop-fdaftc-workshop-competitive-marketplace-biosimilars-03092020-03092020#event-information. (Accessed 26 May 2021).
[2] A. Sharma, N. Kumar, B.D. Kuppermann, et al. Biologics, biosilimars, and biobetters: different terms or different drugs? Eye 2019;33:1032–1034.
[3] ThePharmaLetter, 2011. Glycotope enrolls first patient for 'biobetter' of Roche cancer drug Herceptin. https://www.thepharmaletter.com/article/glycotope-enrolls-first-patient-for-biobetter-of-roche-cancer-drug-herceptin. (Accessed 26 May 2021).
[4] H. Mellstedt. Clinical considerations for biosimilar antibodies. EJC Suppl. 2013;11(3):1-11.
[5] M. Kesik‐Brodacka. Progress in biopharmaceutical development. Biotechnol Appl Biochem. 2017;65(3):306-322.
[6] U.S. Food and Drug Administration, 2006. The Road to the Biotech Revolution – Highlights of 100 Years of Biologics Regulation. https://www.fda.gov/files/about%20fda/published/The-Road-to-the-Biotech-Revolution--Highlights-of-100-Years-of-Biologics-Regulation.pdf. (Accessed 26 May 2021).
[7] U.S. Food and Drug Administration, 2021. Development & Approval Process (CBER). https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber. (Accessed 26 May 2021).
[8] U.S. Food and Drug Administration, 2017. Center for Drug Evaluation and Research: Biosimilars and Interchangeable Products. https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products. (Accessed 26 May 2021).
[9] European Medicines Agency, 2019. Biosimilars in the EU, Information guide for healthcare professionals. https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf. (Accessed 26 May 2021).
[10] European Medicines Agency, 2020. Biosimilar medicines: marketing authorization. https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/biosimilar-medicines-marketing-authorisation. (Accessed 26 May 2021).
[11] U.S. Food and Drug Administration, 2009. Center for Drug Evaluation and Research: Implementation of the Biologics Price Competition and Innovation Act. https://www.fda.gov/drugs/guidance-compliance-regulatory-information/implementation-biologics-price-competition-and-innovation-act-2009. (Accessed 26 May 2021).
[12] A. Beck. Biosimilar, biobetter and next generation therapeutic antibodies. MAbs. 2011;3(2):107-110.
[13] WR. Strohl. Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters. BioDrugs. 2015;29(4):215-239.
[14] Creative Biolabs. Fc Engineered Anti-Human CD30 Therapeutic Antibody, a CDC-Enhanced Biobetter. https://adcc.creative-biolabs.com/fc-engineered-anti-human-cd30-therapeutic-antibody-a-cdc-enhanced-biobetter-lot-cb20-pz36-84.htm. (Accessed 26 May 2021).
[15] Q. An, Y. Zheng, Y. Zhao, et. al. Physicochemical characterization and phase I study of CMAB008, an infliximab biosimilar produced by a different expression system. Drug Des Devel Ther. 2019;13:791-805
[16] A.D. AlQahtani, L. Al-Mansoori, S.S. Bashraheel, et. al. Production of "biobetter" variants of glucarpidase with enhanced enzyme activity. Biomed Pharmacother. 2019;112:108725
[17] ClinicalTrials.gov, 2015. Study of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) for On-demand Treatment of Bleeding Episodes in Patients With Hemophilia A or B With Inhibitors. https://clinicaltrials.gov/ct2/show/NCT02484638. (Accessed 26 May 2021).
[18] W. Jelkmann. Physiology and pharmacology of erythropoietin. Transfus Med Hemother. 2013;40(5):302-309.
[19] Y.J. Kim, S. Ertan-Ahmed, Y. Capan, et. al. Preclinical evaluation of a biobetter candidate: Pharmacokinetics and pharmacodynamics of GX‐G3 in healthy and neutropenia‐induced rats. Drug Dev Res. 2019;80(6):807-813.
[20] A.D. AlQahtani, L. Al-Mansoori, S.S. Bashraheel, et al. Production of "biobetter" glucarpidase variants to improve drug detoxification and antibody directed enzyme prodrug therapy for cancer treatment. Eur J Pharm Sci. 2019;127:79-91.
[21] R. Reski, J. Parsons, E. Decker. Moss‐made pharmaceuticals: from bench to bedside. Plant Biotechnology Journal. 2015;13(8):1191-1198.
[22] ClinicalTrials.gov, 2013. A Study of MM-111 and Paclitaxel With Trastuzumab in Patients HER2 Positive Carcinomas of the Distal Esophagus, Gastroesophageal (GE) Junction and Stomach. https://clinicaltrials.gov/ct2/show/NCT01774851. (Accessed 26 May 2021).
[23] T. Feltes, H. Sondheimer, R. Tulloh, et. al. Motavizumab Cardiac Study Group. A Randomized Controlled Trial of Motavizumab Versus Palivizumab for the Prophylaxis of Serious Respiratory Syncytial Virus Disease in Children with Hemodynamically Significant Congenital Heart Disease. Pediatr Res. 2011;70:186–191
[24] L.P. Brumano, F.V.S. da Silva, T.A. Costa-Silva, et al. Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles. Front Bioeng Biotechnol. 2019;6:212.
[25] F. Courtois, N.J. Agrawal, T.M. Lauer, et.al. Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab. MAbs. 2016;8(1):99-112.
[26] K. Song, I.S. Yoon, N.A. Kim, et al. Glycoengineering of interferon-β 1a improves its biophysical and pharmacokinetic properties. PLoS One. 2014;9(5):e96967.
[27] ClinicalTrials.gov, 2014. Versartis Long-Term Safety Study of Somavaratan (VISTA). https://clinicaltrials.gov/ct2/show/NCT02068521. (Accessed 26 May 2021).
[28] Creative Biolabs. Non-Fucosylated Anti-Human HER2 (TrasGEX) Therapeutic Antibody, an ADCC-Enhanced Biobetter. https://adcc.creative-biolabs.com/non-fucosylated-anti-human-her2-trasgex-therapeutic-antibody-an-adcc-enhanced-biobetter-2614.htm. (Accessed 26 May 2021).
[29] R. De Santis. Anti-ErbB2 immunotherapeutics: struggling to make better antibodies for cancer therapy. MAbs. 2020;12(1):1725346.
[30] A.A. Lugovskoy, J.M. Reichert, A. Beck. 7th annual European Antibody Congress 2011: November 29-December 1, 2011, Geneva, Switzerland. MAbs. 2012;4(2):134-152.
[31] ClinicalTrials.gov, 2015. Study of TV-1106 in Growth Hormone-Deficient Adults.
https://clinicaltrials.gov/ct2/show/NCT02410343 (Accessed 26 May 2021).
[32] W. Jelkmann. Physiology and Pharmacology of Erythropoietin. Transfus Med Hemotherapy. 2016;40(5):302-309.
[33] U.S. Food and Drug Administration, 2017. Center for Drug Evaluation and Research. Information for Epogen/Procrit (Epoetin alfa). https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-epogenprocrit-epoetin-alfa. (Accessed 26 May 2021).
[34] U.S. Food and Drug Administration, 2007. Methoxy polyethylene glycol-epoetin beta (MIRCERA) Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125164s078lbl.pdf. (Accessed 26 May 2021).
[35] U.S. Food and Drug Administration, 2013. Obinutuzumab GAZYVA® Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125486s017s018lbl.pdf. (Accessed 26 May 2021).
[36] U.S. Food and Drug Administration, 2020. RIABNI (rituximab-arrx) Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761140s000lbl.pdf. (Accessed 19 December 2021).
[37] S. Ertan-Ahmed, M.G. Kiehl, A. Radinoff, et. al. GX-G3, a long-acting G-CSF, compared with pegfilgrastim in reducing duration of severe neutropenia after chemotherapy for non-Hodgkin’s lymphoma. J Clin Oncol. 2019;37(15):e19065.
[38] ClinicalTrials.gov, 2011. TrasGEX™: Dose Escalation Study. https://clinicaltrials.gov/ct2/show/NCT01409343. (Accessed 26 May 2021).
[39] A. Beck, L. Goetsch, C. Dumontet, et. al. Strategies and challenges for the next generation of antibody–drug conjugates. Nat Rev Drug Discov. 2017;16:315–337.
[40] U.S. Food and Drug Administration, 2011. Brentuximab Vedotin (Adcentris) Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125388_S056S078lbl.pdf. (Accessed 26 May 2021).
[41] ClinicalTrials.gov, 2010. A Phase 1 Study of Brentuximab Vedotin Combined With Multi-Agent Chemotherapy for Hodgkin Lymphoma. https://clinicaltrials.gov/ct2/show/NCT01060904. (Accessed 26 May 2021).
[42] ClinicalTrials.gov, 2012. A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma. https://clinicaltrials.gov/ct2/show/NCT01712490. (Accessed 26 May 2021).
[43] ClinicalTrials.gov, 2013. ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas. https://clinicaltrials.gov/ct2/show/NCT01777152. (Accessed 26 May 2021).
[44] Creative Biolabs. Non-fucosylated Anti-Human RSV F Therapeutic Antibody, an ADCC-Enhanced Biobetter. https://adcc.creative-biolabs.com/afucosylated-anti-human-rsv-f-therapeutic-antibody-an-adcc-enhanced-biobetter-lot-cb20-pz430-476.htm. (Accessed 26 May 2021).
[45] A.L. Sirén, T. Faßhauer, C. Bartels, et. al. Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system. Neurotherapeutics. 2009;6:108–127.
[46] N. Kaneko, E. Kako, K. Sawamoto. Enhancement of ventricular‐subventricular zone‐derived neurogenesis and oligodendrogenesis by erythropoietin and its derivatives. Front. Cell. Neurosci. 2013;7:235.
[47] B. Peng, G. Kong, C. Yang, et. al. Erythropoietin and its derivatives: from tissue protection to immune regulation. Cell Death Dis. 2020;11:79.
[2] A. Sharma, N. Kumar, B.D. Kuppermann, et al. Biologics, biosilimars, and biobetters: different terms or different drugs? Eye 2019;33:1032–1034.
[3] ThePharmaLetter, 2011. Glycotope enrolls first patient for 'biobetter' of Roche cancer drug Herceptin. https://www.thepharmaletter.com/article/glycotope-enrolls-first-patient-for-biobetter-of-roche-cancer-drug-herceptin. (Accessed 26 May 2021).
[4] H. Mellstedt. Clinical considerations for biosimilar antibodies. EJC Suppl. 2013;11(3):1-11.
[5] M. Kesik‐Brodacka. Progress in biopharmaceutical development. Biotechnol Appl Biochem. 2017;65(3):306-322.
[6] U.S. Food and Drug Administration, 2006. The Road to the Biotech Revolution – Highlights of 100 Years of Biologics Regulation. https://www.fda.gov/files/about%20fda/published/The-Road-to-the-Biotech-Revolution--Highlights-of-100-Years-of-Biologics-Regulation.pdf. (Accessed 26 May 2021).
[7] U.S. Food and Drug Administration, 2021. Development & Approval Process (CBER). https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber. (Accessed 26 May 2021).
[8] U.S. Food and Drug Administration, 2017. Center for Drug Evaluation and Research: Biosimilars and Interchangeable Products. https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products. (Accessed 26 May 2021).
[9] European Medicines Agency, 2019. Biosimilars in the EU, Information guide for healthcare professionals. https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf. (Accessed 26 May 2021).
[10] European Medicines Agency, 2020. Biosimilar medicines: marketing authorization. https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/biosimilar-medicines-marketing-authorisation. (Accessed 26 May 2021).
[11] U.S. Food and Drug Administration, 2009. Center for Drug Evaluation and Research: Implementation of the Biologics Price Competition and Innovation Act. https://www.fda.gov/drugs/guidance-compliance-regulatory-information/implementation-biologics-price-competition-and-innovation-act-2009. (Accessed 26 May 2021).
[12] A. Beck. Biosimilar, biobetter and next generation therapeutic antibodies. MAbs. 2011;3(2):107-110.
[13] WR. Strohl. Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters. BioDrugs. 2015;29(4):215-239.
[14] Creative Biolabs. Fc Engineered Anti-Human CD30 Therapeutic Antibody, a CDC-Enhanced Biobetter. https://adcc.creative-biolabs.com/fc-engineered-anti-human-cd30-therapeutic-antibody-a-cdc-enhanced-biobetter-lot-cb20-pz36-84.htm. (Accessed 26 May 2021).
[15] Q. An, Y. Zheng, Y. Zhao, et. al. Physicochemical characterization and phase I study of CMAB008, an infliximab biosimilar produced by a different expression system. Drug Des Devel Ther. 2019;13:791-805
[16] A.D. AlQahtani, L. Al-Mansoori, S.S. Bashraheel, et. al. Production of "biobetter" variants of glucarpidase with enhanced enzyme activity. Biomed Pharmacother. 2019;112:108725
[17] ClinicalTrials.gov, 2015. Study of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) for On-demand Treatment of Bleeding Episodes in Patients With Hemophilia A or B With Inhibitors. https://clinicaltrials.gov/ct2/show/NCT02484638. (Accessed 26 May 2021).
[18] W. Jelkmann. Physiology and pharmacology of erythropoietin. Transfus Med Hemother. 2013;40(5):302-309.
[19] Y.J. Kim, S. Ertan-Ahmed, Y. Capan, et. al. Preclinical evaluation of a biobetter candidate: Pharmacokinetics and pharmacodynamics of GX‐G3 in healthy and neutropenia‐induced rats. Drug Dev Res. 2019;80(6):807-813.
[20] A.D. AlQahtani, L. Al-Mansoori, S.S. Bashraheel, et al. Production of "biobetter" glucarpidase variants to improve drug detoxification and antibody directed enzyme prodrug therapy for cancer treatment. Eur J Pharm Sci. 2019;127:79-91.
[21] R. Reski, J. Parsons, E. Decker. Moss‐made pharmaceuticals: from bench to bedside. Plant Biotechnology Journal. 2015;13(8):1191-1198.
[22] ClinicalTrials.gov, 2013. A Study of MM-111 and Paclitaxel With Trastuzumab in Patients HER2 Positive Carcinomas of the Distal Esophagus, Gastroesophageal (GE) Junction and Stomach. https://clinicaltrials.gov/ct2/show/NCT01774851. (Accessed 26 May 2021).
[23] T. Feltes, H. Sondheimer, R. Tulloh, et. al. Motavizumab Cardiac Study Group. A Randomized Controlled Trial of Motavizumab Versus Palivizumab for the Prophylaxis of Serious Respiratory Syncytial Virus Disease in Children with Hemodynamically Significant Congenital Heart Disease. Pediatr Res. 2011;70:186–191
[24] L.P. Brumano, F.V.S. da Silva, T.A. Costa-Silva, et al. Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles. Front Bioeng Biotechnol. 2019;6:212.
[25] F. Courtois, N.J. Agrawal, T.M. Lauer, et.al. Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab. MAbs. 2016;8(1):99-112.
[26] K. Song, I.S. Yoon, N.A. Kim, et al. Glycoengineering of interferon-β 1a improves its biophysical and pharmacokinetic properties. PLoS One. 2014;9(5):e96967.
[27] ClinicalTrials.gov, 2014. Versartis Long-Term Safety Study of Somavaratan (VISTA). https://clinicaltrials.gov/ct2/show/NCT02068521. (Accessed 26 May 2021).
[28] Creative Biolabs. Non-Fucosylated Anti-Human HER2 (TrasGEX) Therapeutic Antibody, an ADCC-Enhanced Biobetter. https://adcc.creative-biolabs.com/non-fucosylated-anti-human-her2-trasgex-therapeutic-antibody-an-adcc-enhanced-biobetter-2614.htm. (Accessed 26 May 2021).
[29] R. De Santis. Anti-ErbB2 immunotherapeutics: struggling to make better antibodies for cancer therapy. MAbs. 2020;12(1):1725346.
[30] A.A. Lugovskoy, J.M. Reichert, A. Beck. 7th annual European Antibody Congress 2011: November 29-December 1, 2011, Geneva, Switzerland. MAbs. 2012;4(2):134-152.
[31] ClinicalTrials.gov, 2015. Study of TV-1106 in Growth Hormone-Deficient Adults.
https://clinicaltrials.gov/ct2/show/NCT02410343 (Accessed 26 May 2021).
[32] W. Jelkmann. Physiology and Pharmacology of Erythropoietin. Transfus Med Hemotherapy. 2016;40(5):302-309.
[33] U.S. Food and Drug Administration, 2017. Center for Drug Evaluation and Research. Information for Epogen/Procrit (Epoetin alfa). https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-epogenprocrit-epoetin-alfa. (Accessed 26 May 2021).
[34] U.S. Food and Drug Administration, 2007. Methoxy polyethylene glycol-epoetin beta (MIRCERA) Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125164s078lbl.pdf. (Accessed 26 May 2021).
[35] U.S. Food and Drug Administration, 2013. Obinutuzumab GAZYVA® Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125486s017s018lbl.pdf. (Accessed 26 May 2021).
[36] U.S. Food and Drug Administration, 2020. RIABNI (rituximab-arrx) Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761140s000lbl.pdf. (Accessed 19 December 2021).
[37] S. Ertan-Ahmed, M.G. Kiehl, A. Radinoff, et. al. GX-G3, a long-acting G-CSF, compared with pegfilgrastim in reducing duration of severe neutropenia after chemotherapy for non-Hodgkin’s lymphoma. J Clin Oncol. 2019;37(15):e19065.
[38] ClinicalTrials.gov, 2011. TrasGEX™: Dose Escalation Study. https://clinicaltrials.gov/ct2/show/NCT01409343. (Accessed 26 May 2021).
[39] A. Beck, L. Goetsch, C. Dumontet, et. al. Strategies and challenges for the next generation of antibody–drug conjugates. Nat Rev Drug Discov. 2017;16:315–337.
[40] U.S. Food and Drug Administration, 2011. Brentuximab Vedotin (Adcentris) Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125388_S056S078lbl.pdf. (Accessed 26 May 2021).
[41] ClinicalTrials.gov, 2010. A Phase 1 Study of Brentuximab Vedotin Combined With Multi-Agent Chemotherapy for Hodgkin Lymphoma. https://clinicaltrials.gov/ct2/show/NCT01060904. (Accessed 26 May 2021).
[42] ClinicalTrials.gov, 2012. A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma. https://clinicaltrials.gov/ct2/show/NCT01712490. (Accessed 26 May 2021).
[43] ClinicalTrials.gov, 2013. ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas. https://clinicaltrials.gov/ct2/show/NCT01777152. (Accessed 26 May 2021).
[44] Creative Biolabs. Non-fucosylated Anti-Human RSV F Therapeutic Antibody, an ADCC-Enhanced Biobetter. https://adcc.creative-biolabs.com/afucosylated-anti-human-rsv-f-therapeutic-antibody-an-adcc-enhanced-biobetter-lot-cb20-pz430-476.htm. (Accessed 26 May 2021).
[45] A.L. Sirén, T. Faßhauer, C. Bartels, et. al. Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system. Neurotherapeutics. 2009;6:108–127.
[46] N. Kaneko, E. Kako, K. Sawamoto. Enhancement of ventricular‐subventricular zone‐derived neurogenesis and oligodendrogenesis by erythropoietin and its derivatives. Front. Cell. Neurosci. 2013;7:235.
[47] B. Peng, G. Kong, C. Yang, et. al. Erythropoietin and its derivatives: from tissue protection to immune regulation. Cell Death Dis. 2020;11:79.