Still there are large medical needs that are not met with efficacious drugs. It has for example been an explosion in our understanding of cancer biology but our ability to translate these advances into therapies is poor [1]. To developing new drugs is, however, far from an easy task. It demands scientific competence, theoretically as well as practically, integrity, creativity, engagement, responsibility and, not at least, critical thinking.

  Before 1990, the Swedish pharma industry was efficient to discover and develop new drugs that met large medical needs, e.g., terbutaline (Bricanyl), felodipin (Plendil), metoprolol (Seloken) and omeprazol (Losec), together with several others. The research organizations at Draco and Hässle, who developed these best-sellers, were small but with great scientific competence, creativity and innovative capability. Terbutaline was actually discovered before β-adrenoceptors were divided into β1- and β2-receptors, personal communication from my opponent professor Torsten Olsson at my public defense of the PhD thesis. Olsson was central in the terbutaline project. In 1967 Lands reported that there were two types of β-adrenoceptors, β1 and β2 [2]. Terbutaline is a selective β2 agonist. At that time the same person often followed the drug all the way from discovery to marketing. As preclinical member of the iodixanol (Visipaque) team I experienced the same culture in Norway. I started working for Nycomed Imaging in Oslo 1992 and Visipaque was launched 1995. It was really exciting to be a member of the project group during the early marketing period, which among other things included teaching the sales organization of Nycomed Imaging why Visipaque was a better x-ray contrast medium than its forerunners. This was far from an easy task taking in consideration the success with its forerunner iohexol (Omnipaque). Interestingly, Nycomed Imaging still in 1995 worked in accordance to the “Swedish model” (see below), whereas Swedish companies long before had left it and gone into the mega-merger era characterized by a never-ending reorganizations of R&D. In addition the small Swedish companies, and also the Norvegian companies, had a close collaboration with outstanding Swedish and Norwegain researchers, such as the professor of pharmacology Arvid Carlsson (1923-2018; Nobel laureate in physiology or medicine 2000), professor of radiology Torsten Almén (1931 – 2016) (see photo) and professor of nephrology Knut Joakim Berg (1930-2017). When it came to the final formulation of Visipaque, Nycomed Imaging’s American collaborator Sterling Winthrop wanted to add “physiological concentration of calcium ions” to it, apparently because it would sound god when promoting Visipaque. Almén together with a few other scientists realized that such a formulation would put patients, particularly during coronary angiography, in real danger because of increased risk of ventricular fibrillation. The Management of Nycomed Imaging was ambivalent for Sterling Winthrop’s arguments but not Almén! Later on competitors argue but without any proof that Visipaque was more nephrotoxic than its forerunners. Knut Joakim Berg on the other hand was convinced from his clinical experience with Visipaque that it was less nephrotoxic. This was a critical issue for Visipaque and Nycomed Imaging once again was ambivalent but Berg managed to convince them to conduct a study. This study published in New England Journal of Medicine [3] showed exactly what Berg had predicted, i.e., Visipaque was less nephrotoxic than its forerunners. As a result the sale of Visipaque increased tremendously.

References

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Citation

Citation: Jan Olof G Karlsson. “Swedish Model of Developing Innovative Drugs: What Happened and Why?". Acta Scientific Pharmaceutical Sciences 4.1 (2020): 55-58.