Man has used biologic agents to create valuable products for 6,000 years. The Babylonians and Sumerians used yeast to create beer and the Egyptians and Chinese developed processes using microorganisms to create yogurt, bread, cheese, and wine. Now modern pharmaceutical companies are using Chinese hamster ovary as well as other living cells to create a wide variety of biologically active products for medical purposes. The number and variety of proteins and related biologic compounds available to physicians have increased rapidly over the past several years.
It has been postulated that most human disease is the result of either a dysfunctional, over- or under-expression of a specific protein. Small molecules target an estimated 500 of these receptors or proteins. The Human Genome Project, begun in 1990 and completed just 10 years later, estimates that humans house nearly 30,000 different genes that code for nearly 400,000 different proteins, significantly increasing the potential targets for medicine to focus their curative powers on.
Time magazine stated in July 3, 2000: "After more than a decade ... the human genome project has deciphered essentially all the 3.1 billion biochemical letters of human DNA ...[and] in a matter of decades, the world of medicine will be utterly transformed, and history books will mark this week as the ceremonial start of the genomic era." Now, just 50 years after the discovery of the structure of DNA by 25-year-old James Watson and 36-year-old Francis Crick, the explosion is just starting. Little could they have imagined the spectacular developments that their little noticed press release on Feb. 28, 1953 have spawned.
In 2002 a new biologic was released approximately every five and a half weeks. This followed a 2001 release rate of one every six and a half weeks. This rate should continue, as there will be an estimated total of 197 biologic medications available, creating a market of nearly $40 billion in annual revenue by the end of 2004. However, there is an equal amount of development in the device sector that is just as amazing.
This is the first in a series of monthly columns that will discuss biotechnology and biomedical technology and the impact of new technology on managed care. Much of what will be discussed will revolve around the plethora of drugs created from living cells — commonly called biotech drugs. Other technology products contain organic substances that do not necessarily involve cells in the actual production, but result in polypeptides that exert a significant influence on disease processes.
Future columns will discuss photo-activated drugs such as Photofrin (porfimer sodium), a unique cancer therapy that consists of the injection of a photosensitizing agent followed by a specific wavelength light treatment. The laser is not a thermal laser and has no effect on its own without the sensitizing agent. Together the activation porfimer causes a series of reactions that destroys tumors and pre-cancerous lesions. Although currently indicated only for cancer of the esophagus and lung, recent FDA activity predicts approval for a much more common disease.
This column will also explore Deflux (dextranomer/hyaluronic acid copolymer microspheres in a viscous gel), which is injected sub-mucosally in the urinary bladder in close proximity to the ureteral orifice under direct visualization in infants with vesicoureteral reflux. This injection creates increased tissue bulk thereby providing a valve-like effect that reduces or eliminates reflux. This new approach prevents a significant surgical procedure in a fragile population.
Other recent developments will be discussed, such as the newly released protein that will dramatically change the way that psoriasis is treated. At what point is psoriasis a medical problem and ceases to be just a cosmetic problem that will cost up to $20,000 per year just for the injectable treatment?
Not to be ignored is the field of cancer. There have been dramatic events in this arena. Virtually no one has missed the ImClone Systems controversy. Although this has added a particularly dark cloud to the biotech arena, the developments in the cancer sector are nothing short of astonishing. Of course, most of us are probably aware of the HER 2 specific protein, Herceptin. This drug is unique due to the specific HER 2 protein testing that must be done in order to determine appropriate patients. Although by itself this targeted approach was a startling approach to cancer, newer drugs are even more fascinating.
We now have a drug that is a mixture of the diphtheria toxin paired with a smart bomb-like protein, interleukin. This drug Ontak (denileukin deftitox) will seek out tumor cells, be drawn into the cells, cleaved to release the toxic effects of the protein from the diphtheria organism, stop protein synthesis and destroy the cell. Another drug Bexxar (iodine-131 tositumomab), is created using a radioactive element that likewise is paired with a protein that seeks a specific receptor that is present on tumor cells. The monoclonal antibody attaches to the tumor and the radioactive iodine destroys the cell. In all, Pharmaceutical Research and Manufacturers of America estimates that about 175 biologic drugs are in development just for cancer.
Of course we cannot ignore the products that have been developed to replace a deficiency, such as Ceredase (alglucerase injection) or the soon-to-be released treatment for Fabry's disease. The liposomal storage diseases have no other effective treatment.
Other disease categories also have expanding biologic pipelines including 39 for infectious disease, 28 for neurologic disorders, 26 for heart disease, and 22 for respiratory disorders. Still more research focuses on HIV and AIDS, autoimmune disorders and skin diseases. Finally, there are hybrid drug-devices such as the drug-coated cardiovascular stents and the implantable drugs. Such products are fertile ground for discussion.
How will managed care handle this rapid development and release of technology? Perhaps more importantly, how will physicians and the public respond to those constraints that managed care organizations place on their members? How will the government respond? What opportunities do managed care organizations have to develop a proactive rather than a reactive approach? How will employers view these developments? What abuses may occur, such as physicians producing a new, highly lucrative revenue stream by infusing the new products in their offices? How will managed care prevent the decisions from being influenced by the revenue motive? Will there be access to these new technologies for those without insurance?
How will the genomic project affect all of the constituents in the health care arena? These are just a few of the points that this column will focus upon in the coming months.