CHICAGO – When I first started in the pharmaceutical industry some 30 years ago, the prevailing class of pharmaceutical products was antibiotics. This trend was part of the initial globalization of the pharmaceutical industry that began during and soon after World War II.

As part of the war effort then, the U.S. government sought out assistance from companies like Pfizer, Abbott Labs and Squibb (and two other major U.S. companies) to help develop and produce the first major antibiotic: penicillin.

This product, which was discovered by Alexander Fleming in 1928, was not really used to treat patients until a few years later. Quantities of the drug were not easily produced or available (sound like some of the challenges we see with today’s large molecule?).

The first U.S. patients were treated in 1942 with U.S.-made penicillin (just enough for 10 patients), according to Wikipedia. There is an interesting Illinois connection here: a moldy cantaloupe in a Peoria, Ill. market was found to contain the best and highest quality penicillin after a search had been made worldwide.

Further work on this mold and the cantaloupe at the North Regional Research Laboratory in Peoria allowed the U.S. to ramp up production to more than 2 million doses to prepare for the invasion of Normandy.

Penicillin (considered at that time to be the “miracle drug”) played an important role in treating battlefield conditions during World War II. Because of the urgent need for millions of doses and with U.S. government funding support, an industry used to producing vitamins and analgesics (aspirin) up to that time shifted gears and met the need to have this vital drug available.

The discovery of penicillin led to the discovery of other classes of antibiotics during the early 1950s such as tetracyclines, macrolides and other classes. The broader awareness of infectious diseases and the ability of these new classes of antibiotics to treat many of these infections created impetus for the pharmaceutical industry to grow.

Companies like Pfizer, Searle, Abbott Labs (erythromycin) surged forward at the same time beginning their internationalization process in L.A. and Europe, where these new antibiotics could be used in daily life (not just war-time use). The next twenty years, 1950’s – 1970’s was really the “era of antibiotics” as more new classes emerged such as penicillin derivatives like ampicillin, followed by cephalosporins and betalactamases.

During the 1970s, antibiotics began to give way to two other classes of pharmaceuticals: cardiovascular drugs (high blood pressure; cholesterol was barely on the radar screen at that time) with the early use of diuretics and vasodilators leading into beta blockers and then ACE inhibitors and calcium-channel blockers along with psychotherapeutics (the age of Valium and the benzodiazepines).

The following 10 years saw a shift into the development of these classes of drugs as a greater awareness of other societal medicinal needs took place (a pharmaceutical version of Maslow’s hierarchy of needs).

The 1980s saw the emergence of other societal diseases needing new treatment modalities: gastrointestinal (ulcers, which spawned the first blockbuster drug Tagamet) and arthritis (non-steroidal anti-inflammatories) commanded our attention.

The 1990s saw a shift back to cardiovascular drugs (the advent of cholesterol reduction), newer generations of psychotherapeutics for the widening range of disease such as anxiety, bipolar disorder, depression and more recently Alzheimer’s along with a new form of infectious diseases: viruses (and the retroviral drugs used to combat HIV infection) and the development of new vaccines.

Certainly the role of biotechnology (particularly in the last 10 or years) has made us revisit all of the disease areas with renewed vigor as the biotech drugs have offered greater efficacy with less side effects but at much greater patient cost.

Two areas of diseases that have not been in the limelight in the last 30 years, however, have been infectious diseases and cancer. This, though, is changing. While it had seemed that the antibiotics developed in the 1970s to 1990s were good enough, the resurgence of old diseases (and new ones) due to antibiotic resistance by key “bugs” (bacteria) has made it an urgent need to develop new antibiotic strategies.

Similar to the U.S. government’s role in pushing forward the development of the pharma industry in the 1940s and 1950s with the development of penicillin, during the late 1980s and 1990s a large investment was made by the government through the National Cancer Institute (NCI) to combat cancer. This resulted in the development of such drugs as paclitaxel (Bristol-Myers Squibb’s Taxol), which is the first major cancer drug blockbuster.

In 2005, the NCI spent $4.8 billion in R&D funds (an increase of 28 percent over 2001 levels), according to SCRIP. The result has been a shift from the traditional and conventional chemotherapy used for the last 50 years into new treatment modalities such as vaccines, monoclonal antibodies, immunomodulators and other, protein-based therapy.

What’s driving this is the growing recognition and understanding of this disease and the growing disease burden around the world.

The number of annual new cases of oncology around the world is estimated to go from 10 million cases in 2000 to 15 million cases in 2015 (or a growth of 50 percent in 15 years), according to the pharmaceutical publication SCRIP in its May 28 and 30, 2008 edition. This makes cancer the leading global cause of death for people under 85 years of age.

Sixty percent of these cases (or 9 million new cases) are predicted to occur in the U.S. and Western Europe, which is expected to grow even further to 11 million people by 2030. This is not to say that cancer does not exist in Asia, Latin America and other parts of the world. Better diagnosis, awareness and treatment takes place in these regions (as well as an ability to pay for this care).

Another way to look at the growing impact of cancer (at least in the U.S.) is that the cost of cancer in the U.S. was almost $210 billion in 2005 (according to the National Institutes of Health) with direct medical costs (inpatient and outpatient care and drugs and devices) costing about $74 billion or 35 percent of the total, according to the SCRIP article.

The remaining costs are attributed to indirect morbidity (loss of productivity) and indirect mortality (loss of productivity due to early death).

The largest types of cancer on a global basis are lung, colorectal and breast, which represent more than 50 percent of the total. This incidence, however, shifts in certain countries such as the U.S. where prostate cancer now exceeds breast cancer, Japan where stomach cancer is high and Asia in general where liver cancer is of high incidence.

The NCI in the U.S. is not the only health authority around the world to be increasing R&D funding for new treatment (and diagnostic) approaches to cancer.

Many other countries are dedicating significant funds to this medical problem. The issue here is not that cancer is one disease but in fact (as the SCRIP points out) it’s several diseases that are “characterized by uncontrolled cell growth that may be triggered by external (e.g. chemical, viruses, radiation) and internal (e.g. hormones, immunity, genetic) factors”.

The growth in interest in the disease and its prevention, diagnosis and treatment can be evidenced by the attendance at the American Society of Clinical Oncology (ASCO), which was recently held in Chicago. Though final numbers are not available, I would venture that there were upward of 30,000 oncologists from all over the world.

There were also several thousand industry personnel manning the extensive exhibit floor space at McCormick Place, which dwarfed the space at BIO 2008 in San Diego.

The growth in this medical specialty has been not only in the three major divisions of surgery, overall treatment and care and radiology but in specialization in key parts and organs of the body: skin (melanoma), brain, head and neck, lung, prostate, breast, colorectal, ovarian, cervical and blood (leukemias).

For pharmaceutical and biotech companies, the result has been the explosion of the worldwide oncology market (for drugs) with an annual growth rate of 12 percent versus the traditional industry overall growth rate of 4.6 percent (in other words, more than 2.5 times as fast).

In 2006, industry sales of cancer drugs were $35.6 billion (a doubling of the previous level of sales in 2001), which is expected to reach $55 billion by 2011 with another $33 billion in sales of supportive care products. This makes oncology the No. 1 therapeutic class. It’s ahead of cardiology and infectious diseases.

As would be expected, the U.S. represents about 45 percent of the global oncology market with Europe representing another 35 percent and Japan another 10 percent for a total of 90 percent of the world market.

Even more amazing is the oncology R&D investment that’s still happening. According to the SCRIP, cancer drugs represent 30 percent of all drugs in development with more than 650 candidates in Phase II or beyond that stage of development. There are a number of oncology blockbuster drugs today. In fact, 16 of the 75 blockbuster drugs that existed in 2006 were oncology drugs:

1. Roche/Genentech has three of these drugs with combined annual sales of $8.9 billion. This makes them the leading oncology presence. Remember that Roche owns an important chunk of Genentech.
2. Sanofi-Aventis has two products with annual sales of $4.5 billion.
3. Astra-Zeneca has three products with combined sales of $3.7 billion.

Because of the rapid growth of this market, a number of new players have jumped in via acquisitions.

These include Japanese pharma companies such as Takeda (Millennium Pharmaceuticals), Eisai (MGI Pharma) and Astellas (Agensys). Japanese companies are not the only ones, too. A number of other Big Pharma and Big Biotech companies have done the same (e.g. the Roche acquisition of Ventana, the Celgene acquisition of Pharmion and the Amgen acquisition of Abgenix).

Oncology will continue to be a growth market for a number of years for a number of reasons:

1. There are no cures in sight. There is, however, incremental improvement.
2. The need for multiple treatment modalities to attack the different stages of cell growth.
3. The proliferation of new types of cancer (or at least an understanding of these cancers and better detection) due to genetic variations, environment, diet, etc. (e.g. the rise of breast cancer in males).
4. Government R&D initiatives to diagnose and treat the disease.

Additional improvements in cancer diagnosis through the use of biomarkers will lead to substantial growth in this field and earlier and more patient-customized treatment modalities.

Cancer today has become the driving force behind biotech industry growth in a similar manner as infectious diseases were a driving force for growth in the 1940s and 1950s for the pharmaceutical industry. In both cases, substantial government R&D support was critical to making progress in these disease areas. See you soon!