Jürgen Drews

Innovation Deficit in the Pharmaceutical Industry

A quantitative analysis of the drug discovery potential of the pharmaceutical industry leads to the conclusion that the industry is facing an innovation deficit which will be severe enough to incite further consolidations within the industry. The study is based on a quantitative assessment of all preclinical discovery projects in the top 50 pharmaceutical companies. By applying historical success rates for the emergence of development compounds from discovery projects and for the progression of development compounds to launch, the number of new chemical entities (NCEs) to be annually introduced by the industry starting in 1999 can be estimated. The predicted output figures are not sufficient to sustain the pharmaceutical industry as it stands today. While recombinant proteins and monoclonal antibodies developed by or together with biotech companies may compensate for part of the deficit, this output will not be able to revert the situation. Relief may come from new technologies (genomics and gene therapy). Their impact will, however, not fall within the time scope of the present study, which is five to maximally 10 years.

Strategic choices facing the pharmaceutical industry: A case for innovation

The pharmaceutical industry was founded at a time of unusual scientific, political and economic opportunity, but now the industry finds itself facing important choices in a difficult economic and regulatory environment. Only those companies capable of improving the productivity of their R&D departments can remain important players in the future. The author discusses the different approaches to innovation that are available to the leading pharmaceutical companies and argues for the ‘offensive’ strategy.

Biotechnology's metamorphosis into a drug discovery industry.

Building value in biotechnology companies depends on managements ability to leverage technologies into products.

Pharmaceutical innovation between scientific opportunities and economic constraints

New drugs are only developed when sales expectations appear to match the rising expenditures for development. The repertoire of diseases that are seriously addressed by large pharmaceutical companies is shrinking. Genomics offers the promise of inventing and developing more selective therapies for a large number of diseases, but such increases in selectivity almost inevitably lead to therapeutics aimed at smaller patient populations. Scientific opportunity on the one hand and economic constraints on the other are forcing pharmaceutical R&D in different directions. This study tries to quantify the problem and to identify mechanisms through which the apparent conflict may be resolved.

Gene technology and the drugs of tomorrow

The progress of pharmaceutical research depends on three factors: on the evolution of medical needs, on societal attitudes, and on scientific and technical feasibility. Among the factors which are ‘internal’ to science, molecular biology seems to be the most important driving force, at least for the foreseeable future. The influence of molecular biology on pharmaceutical research is occurring in several distinct phases. The first phase was characterized by the use of gene technology as a production instrument for known proteins. In the second phase, gene technology is instrumental in the identification of novel proteins and in the elucidation of their gene structure and physiological function. A great number of proteins which have therapeutic potential will eventually emerge from this phase, with the more important ones like the hematopoietic factors yet to come. During the third phase, gene technology will provide proteins that can serve as pharmacological tools: receptors, ligands, enzymes, cytokines and other proteins provided by gene technology will enable us to open up new fields of pharmacology from which novel drugs, often low molecular weight chemical entities, will emerge. Finally the fourth phase will be characterized by a knowledge of gene structure and regulation extensive enough to develop a pharmacology of gene regulation and to establish somatic gene therapy. New drugs that can be expected to emerge from the interaction of molecular biology and pharmaceutical research within the next ten to twelve years are discussed. It is expected that pharmaceutical research will in the end be transformed into a discipline in which molecular biology and structural chemistry play dominating roles while synthetic chemistry will be reduced to the role of an important tool.

Definition and History

Immunopharmacology is a still young pharmacological and therapeutic discipline that has grown out of the increasingly more closely interconnected “classical” fields of immunology and pharmacology. The term “immunopharmacology” has been in regular, though not necessarily precise use for about fifteen years only. To some people, immunopharmacology means the effect of pharmaceutical agents on the immune system and its functions, and where these agents come from is of little significance — they may be endogenous, synthetic or of microbial origin. Others tend to consider immunopharmacology as the achievement of pharmacological effects with immunological products, i.e. with antibodies, lymphokines and other factors, mostly consisting of proteins. For clinicians, on the other hand, immunopharmacology is more likely to be the basis for treatment of diseases of the immune system, particularly the autoimmune diseases and anaphylactic and atopic reactions.

Strategies for Successfully Managing Pharmaceutical Research and Development in the 1990s

This paper examines the various environmental pressures facing the pharmaceutical industry and discusses some of the strategic approaches that companies are implementing in response. The challenge is to provide innovative therapeutic modulates that, on the one hand, satisfy a medical need and, on the other hand, provide financial rewards that stimulate the industry to maintain its traditionally high level of investment in research and development. The challenge is to improve the quality and increase the quantity of novel pharmaceutical products without a commensurate increase in expenditures. The industry is attacking these problems by streamlining their organizations, establishing globalized management procedures, and forming various cooperative relationships such as strategic alliances, joint ventures, mergers, and acquisitions.

Substances with an Antiallergic Effect

Immediate-type hypersensitivity is the hallmark of any allergic reaction. It develops when contact with a specific antigen triggers the formation of IgE antibodies which bind to the Fcɛ receptors of mast cells or basophilic leucocytes. Renewed contact with the same antigen then leads to “bridging”: adjacent antibodies on the cell surface are interconnected by antigen molecules through their antigen-binding portions. At the Fc receptor the antigen-antibody reaction gives rise to a signal that passes through a chain of biochemical reactions which will be described below in some detail. Eventually the signal leads to the release of mediators from the granules of mast cells and basophilic leucocytes.

The Immune System — A Short Introduction to its Structure and Function

The immune system consists of approximately 2 × 1012 lymphocytes, which either circulate freely in the blood or exist within organ-specific spatial structures like the lymph nodes, thymus, spleen and bone-marrow. In a wider sense it also includes the macrophages, which have important antigen-presenting functions and are, in addition, effector cells, and the granulocytes, which are mediator and also effector cells. In terms of cell mass, the lymphocytes alone are equivalent to the liver or the central nervous system and therefore occupy as much space as these organ systems.

Antibodies as Immunopharmacological Agents

Approximately a century ago, xenogeneic antibodies against diphtheria toxin were first used by Emil von Behring and his Japanese colleague Shibasaburo Kitasato to treat children who were suffering from the life-threatening complications of diphtheria. Although not all of these early therapeutic attempts were successful, “serum therapy” or “passive immunization” proved to be a highly effective approach to the prophylaxis and treatment of many infectious diseases. In 1901 Emil von Behring was awarded the first Nobel Prize in Medicine for this ground-breaking achievement which in the words of the Nobel Committee had “opened a new road in the domain of medical science and thereby placed in the hands of the physicians a victorious weapon against illness and death”. In the decades to come, however, progress in this field was slow. Several major hurdles had to be overcome: xenogeneic sera caused disturbing side effects, such as anaphylactic shock, which seriously limited their use. When human antibodies finally became available, they could only be applied intramuscularly. The first antibody preparations for intravenous administration had a very short biological half-life and were functionally unreliable. Many avenues of experimentation had to be probed before human antibody preparations became widely available which could be applied intravenously, were well tolerated and retained all the important biological properties of native antibodies. These new preparations have furnished many new opportunities for the treatment of infectious diseases and other disorders.