There is a growing and justified concern in the pharmaceutical field for what might be called innovation crisis in the development of novel antibiotics. The issue has gone beyond the health field, having been discussed at a meeting of the World Economic Forum.
The World Health Organization has warned that we are moving into a "post-antibiotic era". It is increasingly common that deaths occur as a result of bacterial infections which are either refractory to all known drugs, or the germs have acquired plasmids which make them resistant to antibiotics to which they were once sensitive.
Since the late 1980s no new kinds of antibiotics have emerged. Between 2011 and 2013, the F.D.A. (Food and Drug Administration) has approved only three novel antibacterial drugs, the lowest number of innovations since the 1940s, when the antibiotic era began. There are experts who do not hide their pessimism. Such is the case of Michael S. Kinch, of Yale Center for Molecular Discovery team.
The pharmaceutical industry has found a goldmine in the field of immunology and genomics for the development of profitable drugs ranging from monoclonal antibodies to the latest gene therapies. Today, pharmaceutical progress is focused on finding personalized treatments for diseases such as cancer and chronic disease, but also in developing new types of vaccines, and new drugs for widely prevalent diseases such as hepatitis.
However, this approach does not contribute significantly to raising the standards of public health. To this aim, antibiotics are a high priority strategy.
An increasing number of antibiotics are removed from the pharmaceutical market each year due to the emergence of resistant micro-organisms, or they are replaced by similar alternatives (the so-called "me too"). The pharmaceutical antibiotic arsenal consists currently (October 2014) of 96 molecules, 17 less than there were around the turn of this century.
An additional concern is the pharmaceutical corporations’ lack of interest in the discovery of new antibiotics; and even less in the search for new sorts of antibiotic molecules. This is due to a lack of sufficient incentives to engage in intellectual adventures of ten years, or longer, in the future, and with no guarantee of success.
In addition, antibiotic research faces a grim future. Its development is difficult and economic benefits may not justify the intellectual and financial investment required. Unlike drugs for diseases that require prolonged treatment, antibiotics are used for short periods, usually a few days or weeks at the most. Moreover, the new antibiotic molecules are prescribed sparingly in order to avoid the development of resistance, exceeding their patent protection time, so the manufacturer does not obtain the profits they expect.
The above problems in the search for new antibiotics can be extended to drugs used to treat HIV infection and its associated disease, AIDS.
Psychiatric and neurological diseases, including Alzheimer's dementia, are a major source of disability in the developed world.
However, biotech pharmaceutical companies have focused disproportionately on personalized therapies, many of which are drugs for "orphan diseases”. With irony, it can be said that "there are more people studying orphan diseases than patients affected by them." Of all drugs approved by the U.S. Food and Drug Administration in the year 2013, 70% were aimed at diseases affecting less than 1% of the population.
It is necessary to give incentives to the pharmaceutical industry. The costs of developing new pharmaceuticals for widely prevalent diseases have increased steadily, lowering profits. According to experts from Eli Lilly in 2010, the estimated cost of marketing a new drug is around $1.8 billion, requiring that each new drug be less toxic and more effective than existing therapies.
However, the development of orphan drugs is cheaper. The requirements for the approval of orphan drugs by the regulatory agencies are less rigorous. Clinical trials are carried out on a smaller number of patients. In addition, the insurance companies include these treatments in their coverage of their clients. Although these drugs are not blockbusters (their global annual turnover rarely exceeds $500 million), investment for their development and marketing is also not as expensive.
“Classic" drugs lose 80% of the market share within 1 year of patent expiry. Whereas biological drugs have an "additional protection" derived from the difficulty in the manufacture of generic versions and standardise these to the original drug.
An important issue is: can fixed incentives to drug manufacturers be established? The system of patent protection has been regarded, so far, as a valid procedure. But experience is showing that it is not enough.
Returning to the subject of antibiotics should relax the requirements for the approval of new drugs, and increase exclusive sales rights for new kinds of antibiotics.
The myth that "market forces" regulate prices does not work, at least in the field of pharmaceutical research. The market (free market) does not represent an incentive for innovation, especially in societies where taxation stifles the desire to take risks.
Zaragoza (Spain), October, 11th, 2014
López-Tricas, JM MD