Release date:2019/8/20 11:21:21

What is PEGylation? What are the PEGylated drugs used for? PEGylation is the process of the strands attachment of the polymer PEG to molecules and macrostructures, such as a drug, therapeutic protein or vesicle, that can improve the safety and efficiency of many therapeutics. The chain binds to the drugs covalently and builds it sterically stable. Thus, the PEGylated proteins or peptides are non-toxic, non-antigenic, non-immunogenic, and highly water-soluble. In addition, it further increases the half-life of the PEGylated drugs and reduces dose frequency by preventing renal excretion of drugs. 

Related: Potential Limitations of PEGylated Therapeutic Proteins

PEGylation products consist of various reagents including linkers, cross-linkers, and labels. Different reagents include AMINE, CARBOXYL, and CARBOXYL PEGylation. The PEGylated drugs currently are used in the treatment of cancer, chronic kidney diseases, hepatitis, multiple sclerosis, hemophilia, and gastrointestinal disorders. ADAGEN manufactured by Enzon Pharmaceuticals, Inc., US was the first PEGylated protein approved by the U.S. Food and Drug Administration (FDA) in March 1990, to enter the market. Since the introduction of ADAGEN, a mass of PEGylated protein and peptide drugs have kept up the footsteps and many others are under clinical trial or under development stages. Among the FDA approved drugs, Pegasys and Neulasta, exceeded $5 billion in 2011. It's worth mentioning that all of the FDA approved drugs contain methoxypoly (ethylene glycol) or mPEG. The list of PEGylated drugs approved by the FDA is shown below. 

List of PEGylated drugs approved by the FDA
Entry Trade Name Company PEGylated entity Indications Average MW of PEGs Approved Year
Macromolecular Drugs
1 Fylnetra  Amneal Pharmaceuticals LLC G-CSF neutropenia 20 kDa 2022
1 Besremi PharmaEssentia Corp Interferon polycythemia vera 40 kDa 2021
2 Skytrofa Ascendis human growth hormone Growth hormone deficiency 4 x 10 kDa 2021
3 Empaveli Apellis Pentadecapeptide Paroxysmal nocturnal hemoglobinuria (PNH) 40 kDa 2021
4 Nyvepria Pfizer Inc. G-CSF Neutropenia Associated with Chemotherapy  20 kDa 2020
5 Esperoct Novo Nordisk recombinant antihemophilic factor hemophilia  A 40 kDa 2019
6 Ziextenzo Sandoz G-CSF infection during chemotherapy 20 kDa 2019
7 Udenyca Coherus Biosciences G-CSF infection during chemotherapy 20 kDa 2018
8 Palynziq BioMarin Pharmaceutical recombinant phenylalanine  ammonia lyase phenylketonuria ~ 9 X 20 kDa 2018
9 Revcovi Leadiant  Bioscience recombinant adenosine deaminase ADA-SCID 80 kDa 2018
10 Fulphila Mylan GmbH G-CSF infection during chemotherapy 20 kDa 2018
11 Asparlas Servier Pharma L-asparaginase leukemia 31-39 x 5 kDa 2018
12 Jivi Bayer Healthcare recombinant antihemophilic factor hemophilia  A 2 X 30 kDa 2017
13 Rebinyn Novo Nordisk recombinant coagulation factor lX hemophilia B 40 kDa 2017
14 Adynovate Baxalta recombinant antihemophilic factor hemophilia  A ≥1 X 20 kDa 2015
15 Plegridy Biogen peginterferon beta-1a multiple  sclerosis 20 kDa 2014
16 Omontys Takeda erythropoietin anemia 2 X 20 kDa 2012
17 Sylatron Merck peginterferon-alfa-2b melanoma 12 kDa 2011
18 Krystexxa Horizon Pharma recombinant  uricase  protein gout 40 X 10 kDa 2010
19 Cimzia UCB antitumor necrosis factor rheumatoid arthritis 40 kDa 2008
20 Mircera Roche erythropoietin anemia 30 kDa 2007
21 Macugen Pfizer aptamer macular degeneration 2 X 20 kDa 2004
22 Somavert Pfizer human growth hormone acromegaly 4-6 X 5 kDa 2003
23 Neulasta Amgen G-CSF infection during chemotherapy 20 kDa 2002
24 Pegasys Roche peginterferon-alfa-2a hepatitis B and C 40 kDa 2002
25 Pegintron Schering peginterferon-alfa-2b hepatitis C, melanoma 12 kDa 2001
26 Oncaspar Enzon asparaginase leukemia 69-82 X 5 kDa 1994
27 Adagen Enzon adenosine deaminase ADA-SCIO 11-17 X 5 kDa 1990
Small Molecular Drugs
28 Movantik AstraZeneca naloxone constipation 339 Da 2014
29 Asclera Chemische Fabrik Kreussler dodecyl alcohol varicose veins 400 Da 2010
30 Doxil Schering liposomal ovarian cancer, multiple myeloma 2 kDa 1995
List of drugs containing peg is indicated (number of units) x (MW of each PEG unit). G-CSF: growth colony-stimulating factor.
ADA-SCIO: adenosine deaminase severe combined immune deficiency.

In summary, PEGylation has three main advantages:     

  • Improve pharmacokinetics and pharmacodynamic properties: Studies have shown that after PEGylation, the pharmacokinetic properties in the body will change significantly, including prolonging the plasma half-life, increasing the release of drugs in the body, reducing the renal clearance rate, etc.     
  • Enhance drug stability: After the PEGylation of proteins and peptides, a thicker hydration film will be formed on the surface to prevent aggregation and precipitation. Modification of the linkage between PEG and lipid derivatives (acyl, ether, disulfide bond, etc.) can also increase the stability of liposomes. In addition, the flexible chain of PEG can produce a steric hindrance effect, protect the modification from protease attack, and increase the stability of the modification.       
  • Improve the distribution of the drug in the body: After being modified by PEG, the molecular weight of the drug is increased, which greatly reduces its glomerular filtration effect during systemic administration, thereby reducing its excretion in urine. In addition, PEGylated drugs have improved stability in the systemic circulation and prolonged retention time, which is beneficial to improve the distribution of drugs in the body. In particular, it is beneficial to the accumulation of macromolecular drugs in tumors and inflammatory sites with retention enhancing effects, thereby prolonging the treatment time of the drugs in vivo.

In recent years, with the continuous deepening of research and development, new PEGylated drugs such as modified drugs that use heterobifunctional PEG (X-PEG-Y) as a linker have come out. In the future, with the continuous improvement of modification technology, it is believed that more and more excellent PEGylated drugs will appear to provide patients with more and better treatment options.

Biochempeg provides high-quality PEGylation reagents. These reagents are water soluble, monodisperse, biocompatible, and almost aggregation-free, making them ideal for bioconjugation or crosslinking of proteins, antibodies, peptides, oligonucleotides, or solid surfaces to other macromolecules, therapeutic compounds or other small molecules, and dyes.

Related Articles:
Benefits of Monodisperse PEG Linkers in Drug Development
What is PEGylation? Things About PEGylation Technology and Biopharmaceuticals You Should Know
The Applications of PEGylation Reagents

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