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Molecular pharming’s foot in the FDA’s door: Protalix’s trailblazing story

Abstract

Objectives

This short commentary examines the factors that led to Food and Drug Administration’s approval of the first plant-derived biologic.

Results

In 2012, the first plant-derived protein pharmaceutical (biologic) was approved for commercial use in humans. The product, a recombinant form of human β-glucocerebrosidase marketed as ELELYSO, was developed by Protalix Biotherapeutics (Carmiel, Israel). The foresight to select this particular therapeutic product for development, flawless production pipeline, and serendipity seem to provide the key in explaining how ELELYSO became the first plant-derived biologic to achieve approval by Food and Drug Administration.

Conclusions

While the circumstances that enabled Protalix and its scientists to become the first to arrive at this historic milestone are perhaps unique, it is anticipated that more biologics will follow suit in winning regulatory endorsement.

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Notes

  1. A plant-made poultry vaccine against Newcastle disease virus (created by Dow Agroscience), was approved for use by the US Department of Agriculture in 2006. The vaccine was never commercially produced or used (Vermij 2006).

References

  • Aggarwal S (2009) What’s fueling the biotech engine-2008. Nat Biotechnol 27:987–993

    CAS  Article  PubMed  Google Scholar 

  • Aggarwal SR (2012) What’s fueling the biotech engine-2011–2012. Nat Biotechnol 30:1191–1197

    CAS  Article  PubMed  Google Scholar 

  • Aviezer D, Brill-Almon E, Shaaltiel Y, Hashmueli S, Bartfeld D, Mizrachi S, Liberman Y, Freeman A, Zimran A, Galun E (2009) A plant-derived recombinant human glucocerebrosidase enzyme—a preclinical and phase I investigation. PLoS ONE 4:e4792

    PubMed Central  Article  PubMed  Google Scholar 

  • Bashaw ED, Huang SM, Cote TR, Pariser AR, Garnett CE, Burckart G, Zhang L, Men AY, Le CD, Charlab R, Gobburu JV, Lesko LJ (2011) Clinical pharmacology as a cornerstone of orphan drug development. Nat Rev Drug Discov 10:795–796

    CAS  Article  PubMed  Google Scholar 

  • Bishop BM (2015) Potential and emerging treatment options for Ebola virus disease. Ann Pharmacother 49:196–206

    CAS  Article  PubMed  Google Scholar 

  • Brumshtein B, Greenblatt HM, Butters TD, Shaaltiel Y, Aviezer D, Silman I, Futerman AH, Sussman JL (2007) Crystal structures of complexes of N-butyl- and N-nonyl-deoxynojirimycin bound to acid beta-glucosidase: insights into the mechanism of chemical chaperone action in Gaucher disease. J Biol Chem 282:29052–29058

    CAS  Article  PubMed  Google Scholar 

  • Cox TM (2010) Gaucher disease: clinical profile and therapeutic developments. Biologics 4:299–313

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ferraz MJ, Kallemeijn WW, Mirzaian M, Herrera Moro D, Marques A, Wisse P, Boot RG, Willems LI, Overkleeft HS, Aerts JM (2014) Gaucher disease and Fabry disease: new markers and insights in pathophysiology for two distinct glycosphingolipidoses. Biochim Biophys Acta 1841:811–825

    CAS  Article  PubMed  Google Scholar 

  • Hiatt A, Cafferkey R, Bowdish K (1989) Production of antibodies in transgenic plants. Nature 342:76–78

    CAS  Article  PubMed  Google Scholar 

  • Ma JK, Christou P, Chikwamba R, Haydon H, Paul M, Ferrer MP, Ramalingam S, Rech E, Rybicki E, Wigdorowitz A, Yang DC, Thangaraj H (2013) Realising the value of plant molecular pharming to benefit the poor in developing countries and emerging economies. Plant Biotechnol J 11:1029–1033

    Article  PubMed  Google Scholar 

  • Mason HS, Lam DM, Arntzen CJ (1992) Expression of hepatitis B surface antigen in transgenic plants. Proc Natl Acad Sci USA 89:11745–11749

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  • McCarthy M (2014) US signs contract with ZMapp maker to accelerate development of the Ebola drug. BMJ 349:g5488

    Article  PubMed  Google Scholar 

  • Platt FM (2014) Sphingolipid lysosomal storage disorders. Nature 510:68–75

    CAS  Article  PubMed  Google Scholar 

  • Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, Strong JE, Zeitlin L, Kobinger GP (2014) Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 514:47–53

    PubMed Central  CAS  PubMed  Google Scholar 

  • Ratner M (2010) Pfizer stakes a claim in plant cell-made biopharmaceuticals. Nat Biotechnol 28:107–108

    CAS  Article  PubMed  Google Scholar 

  • Reisch MS (2013) Protalix reaches deal with Brazil. Chem Eng News 91:11

    Article  Google Scholar 

  • Rubin EJ, Baden LR (2014) Out of Africa—caring for patients with Ebola. N Engl J Med 371:2430–2432

    Article  PubMed  Google Scholar 

  • Rybicki EP (2014) Plant-based vaccines against viruses. Virol J 11:205

    PubMed Central  Article  PubMed  Google Scholar 

  • Shaaltiel Y, Bartfeld D, Hashmueli S, Baum G, Brill-Almon E, Galili G, Dym O, Boldin-Adamsky SA, Silman I, Sussman JL, Futerman AH, Aviezer D (2007) Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher’s disease using a plant cell system. Plant Biotechnol J 5:579–590

    CAS  Article  PubMed  Google Scholar 

  • Sijmons PC, Dekker BM, Schrammeijer B, Verwoerd TC, van den Elzen PJ, Hoekema A (1990) Production of correctly processed human serum albumin in transgenic plants. Biotechnology (NY) 8:217–221

    CAS  Article  Google Scholar 

  • Stoger E, Fischer R, Moloney M, Ma JK (2014) Plant molecular pharming for the treatment of chronic and infectious diseases. Annu Rev Plant Biol 65:743–768

    CAS  Article  PubMed  Google Scholar 

  • Tekoah Y, Tzaban S, Kizhner T, Hainrichson M, Gantman A, Golembo M, Aviezer D, Shaaltiel Y (2013) Glycosylation and functionality of recombinant beta-glucocerebrosidase from various production systems. Biosci Rep 33:e00071

    PubMed Central  Article  PubMed  Google Scholar 

  • Vermij P (2006) USDA approves the first plant-based vaccine. Mol Biol Evol 24:234

    Google Scholar 

  • Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Munoz ET, Solorio-Meza SE, Amato D, Duran G, Giona F, Heitner R, Rosenbaum H, Giraldo P, Mehta A, Park G, Phillips M, Elstein D, Altarescu G, Szleifer M, Hashmueli S, Aviezer D (2011) Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood 118:5767–5773

    CAS  Article  PubMed  Google Scholar 

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Acknowledgments

TSM’s research was funded in part by work was supported in part by the National Institute for Drug Abuse Program Grant P1 DA031340 awarded to the Mayo Clinic and subcontracted to ASU and in part by the National Institute for General Medical Sciences U54 GM094599.

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Correspondence to Tsafrir S. Mor.

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Mor, T.S. Molecular pharming’s foot in the FDA’s door: Protalix’s trailblazing story. Biotechnol Lett 37, 2147–2150 (2015). https://doi.org/10.1007/s10529-015-1908-z

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  • DOI: https://doi.org/10.1007/s10529-015-1908-z

Keywords

  • Plant-derived biologics
  • FDA-approval
  • Gaucher’s disease
  • Ebola
  • Molecular pharming