The pharmaceutical industry went through a major paradigm change in their product development strategy during the last decade, with the advent of biologics especially monoclonal antibodies. Until recently they were very much focused on small organic molecule based drug development. Things started changing when more and more protein based biologics got approvals and some became blockbuster drugs. Also poor success rate recently with small molecules have contributed to this change.
The global monoclonal antibody drug market, presently worth $30 billion, is probably the fastest growing segment in pharmaceutical industry recording 14% annual growth rate (versus 0.6% for small molecule). Over 50% of products in development currently are biologics that include monoclonal antibodies and recombinant proteins. It has seen a growth of 50% every year over the last 5 years.
Antibodies are proteins made by cells of immune system of most vertebrates to protect them mainly from infections. They do this by identifying and binding to chemical epitopes unique to the infectious agent or foreign to the host organism, called an antigen. Our genome has developed a vast complex of genes, which by combinatorial reorganization can generate millions of combinations of unique antibodies, one unique antibody per immune cell. When a cell, with its unique antibody, encounters its antigen present on a pathogen it will be triggered to multiply exponentially to generate a large clone of cells making one type of antibody, or monoclonal antibody, to destroy the pathogen.
In 1975 Milstein and Kohler developed a way to artificially generate a monoclonal antibody in the lab, for which they got Nobel Prize in 1984. Since this invention, it was said that the age of monoclonal antibodies as ‘magic bullets’ to cure diseases has arrived. The idea of a ‘Magic bullet’ was first proposed by Paul Ehrlich in 1900’s, that if a compound could be made that selectively targeted a disease causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. It took over 10 years for the first monoclonal antibody drug to get to the market in 1986. Since then monoclonal antibodies has become the most successful class of biotech drugs in history, with 26 approved therapies currently in market, of which many are blockbuster drugs (see table below). They have clinical utility ranging from molecular diagnostics, inflammatory and autoimmune diseases, oncology and infectious diseases.
As Paul Ehrlich envisioned, monoclonal antibodies as ‘magic bullets’ are now used to deliver a toxic payload to target pathogen or cancer cells to cure diseases. There are three types of antibody payloads namely drugs, bacterial protein toxins and radioactivity. Examples of drugs include taxol, doxorubicin, and DM1. Examples of toxins are Diphtheria toxin, Pseudomonas endotoxin, and Ricin. Radioactive payloads include 90Y, 131I, imaging isotopes, as well as radio phosphate (32P and 33P).
Toxic payload is not the only use of monoclonal antibodies as drugs. The major growth areas for monoclonal antibodies include therapeutics antibodies (including toxic payloads) and molecular diagnostics. The major therapeutic segments are Oncology (solid and liquid tumors), autoimmune and inflammatory diseases. Molecular diagnostics include in vivo radio imaging for clot proteins, pulmonary embolism, deep vein thrombosis and in vitro diagnostics such as emergency room drug testing for cocaine, heroin and amphetamine.
I see a bright future for monoclonal antibodies, with over 200 or so in various stages of development for varied indications. Advances in technology are also helping to reduce cost of production, improve efficacy and safety. The perceived bottle neck is in the large scale production needed to meet future market needs. Because monoclonal antibodies are made by live cells, production costs are still high. The rapid advancement in development of biopharmaceuticals and biologics recently has forced the industry to come up better solutions to some of these issues. Some of these drugs could be life saving to many patients around the world, but high cost may be keeping it from their reach. The challenge to the industry is to bring the cost down to be affordable to all.
The global monoclonal antibody drug market, presently worth $30 billion, is probably the fastest growing segment in pharmaceutical industry recording 14% annual growth rate (versus 0.6% for small molecule). Over 50% of products in development currently are biologics that include monoclonal antibodies and recombinant proteins. It has seen a growth of 50% every year over the last 5 years.
Antibodies are proteins made by cells of immune system of most vertebrates to protect them mainly from infections. They do this by identifying and binding to chemical epitopes unique to the infectious agent or foreign to the host organism, called an antigen. Our genome has developed a vast complex of genes, which by combinatorial reorganization can generate millions of combinations of unique antibodies, one unique antibody per immune cell. When a cell, with its unique antibody, encounters its antigen present on a pathogen it will be triggered to multiply exponentially to generate a large clone of cells making one type of antibody, or monoclonal antibody, to destroy the pathogen.
In 1975 Milstein and Kohler developed a way to artificially generate a monoclonal antibody in the lab, for which they got Nobel Prize in 1984. Since this invention, it was said that the age of monoclonal antibodies as ‘magic bullets’ to cure diseases has arrived. The idea of a ‘Magic bullet’ was first proposed by Paul Ehrlich in 1900’s, that if a compound could be made that selectively targeted a disease causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. It took over 10 years for the first monoclonal antibody drug to get to the market in 1986. Since then monoclonal antibodies has become the most successful class of biotech drugs in history, with 26 approved therapies currently in market, of which many are blockbuster drugs (see table below). They have clinical utility ranging from molecular diagnostics, inflammatory and autoimmune diseases, oncology and infectious diseases.
As Paul Ehrlich envisioned, monoclonal antibodies as ‘magic bullets’ are now used to deliver a toxic payload to target pathogen or cancer cells to cure diseases. There are three types of antibody payloads namely drugs, bacterial protein toxins and radioactivity. Examples of drugs include taxol, doxorubicin, and DM1. Examples of toxins are Diphtheria toxin, Pseudomonas endotoxin, and Ricin. Radioactive payloads include 90Y, 131I, imaging isotopes, as well as radio phosphate (32P and 33P).
Toxic payload is not the only use of monoclonal antibodies as drugs. The major growth areas for monoclonal antibodies include therapeutics antibodies (including toxic payloads) and molecular diagnostics. The major therapeutic segments are Oncology (solid and liquid tumors), autoimmune and inflammatory diseases. Molecular diagnostics include in vivo radio imaging for clot proteins, pulmonary embolism, deep vein thrombosis and in vitro diagnostics such as emergency room drug testing for cocaine, heroin and amphetamine.
I see a bright future for monoclonal antibodies, with over 200 or so in various stages of development for varied indications. Advances in technology are also helping to reduce cost of production, improve efficacy and safety. The perceived bottle neck is in the large scale production needed to meet future market needs. Because monoclonal antibodies are made by live cells, production costs are still high. The rapid advancement in development of biopharmaceuticals and biologics recently has forced the industry to come up better solutions to some of these issues. Some of these drugs could be life saving to many patients around the world, but high cost may be keeping it from their reach. The challenge to the industry is to bring the cost down to be affordable to all.
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