Obstetrical complications, often referred to as the "great obstetrical syndromes," are among the most common global causes of mortality and morbidity in young women and their infants. However,... Show moreObstetrical complications, often referred to as the "great obstetrical syndromes," are among the most common global causes of mortality and morbidity in young women and their infants. However, treatments for these syndromes are underdeveloped compared with other fields of medicine and are urgently needed. This current paucity of treatments for obstetrical complications is a reflection of the challenges of drug development in pregnancy. The appetite of pharmaceutical companies to invest in research for obstetrical syndromes is generally reduced by concerns for maternal, fetal, and infant safety, poor definition, and high-risk regulatory paths toward product approval. Notably, drug candidates require large investments for development with an unguaranteed return on investment. Furthermore, the discovery of promising drug candidates is hampered by a poor understanding of the pathophysiology of obstetrical syndromes and their uniqueness to human pregnancies. This limits translational extrapolation and de-risking strategies in preclinical studies, as available for other medical areas, compounded with limited fetal safety monitoring to capture early prenatal adverse reactions. In addition, the ethical review committees are reluctant to approve the inclusion of pregnant women in trials, and in the absence of regulatory guidance in obstetrics, clinical development programs are subject to unpredictable regulatory paths. To develop effective and safe drugs for pregnancy complications, substantial commitment, and investment in research for innovative therapies are needed in parallel with the creation of an enabling ethical, legislative, and guidance framework. Solutions are proposed to enable stakeholders to work with a common set of expectations to facilitate progress in this medical discipline. Addressing this significant unmet need to advance maternal and possibly perinatal health requires the involvement of all stakeholders and specifically patients, couples, and cli-nicians facing pregnancy complications in the dearth of appropriate therapies. This paper focused on the key pharmaceutical research and development challenges to achieve effective and safe treatments for obstetrical syndromes. Show less
Durez, P.; Hoekema, A.; Huizinga, T.; Gazin, M.; Present, E.; Veelaert, D.; ... ; Westhovens, R. 2020
A better understanding of disease pathology, improvements in relevant disease outcomes, better treatment strategies and the development of novel therapies all contribute to improving healthcare and... Show moreA better understanding of disease pathology, improvements in relevant disease outcomes, better treatment strategies and the development of novel therapies all contribute to improving healthcare and treatment options. However, the global drug development model today is under increasing pressure, with very high drug development costs. Collaborative research is critical for bringing together different capabilities and expertise to increase the success of drug development, and large-scale collaborations with multiple partners are becoming increasingly common. Research clusters supported by local governments play an important role in bringing together academic centres, hospitals, scientists, and pharmaceutical and biotechnology industries. The 'triple helix' model, with academia, industry and governments working together, has been an important factor in the successful development of novel therapies. During the past 20 years, Galapagos has worked closely with academic centres, hospitals, governments and pharmaceutical companies to conduct innovative research and to develop a novel therapy for rheumatoid arthritis. These collaborations have brought unique knowledge, expertise and skills together, as well as crucial funding at various stages. Local governments in the Benelux have operated in this triple helix model to provide the necessary environment and to stimulate companies to achieve innovation through collaboration. Although the triple helix has already proved successful, evolution to a quadruple helix that includes patients and patient representatives could be the next step to ensure innovation remains transformational. Show less
