Hereditary diseases pose a great medical problem all over the world. In most cases they are caused by gene mutations, which lead to gene irregularities, resulting in incorrect, excessive or insufficient translational factors, predominantly enzyme production in the body. Improper enzyme activity leads to the emergence of many hereditary diseases, gravely affecting the patient’s quality of life and often requiring lifelong treatment. New biotechnological procedures and a better understanding of the pathophysiology of diseases have enabled the development of multiple gene-based medicines, thus forming the future of treatment for numerous diseases. Gene products as medicines are directed not only to gene-related diseases, but also represent the novel, alternative approach to modify pretranslational pathways, leading to pathophysiological conditions. This master’s thesis focuses on the small interfering RNA-based medicines. Patisiran, givosiran, lumasiran and inclisiran are the leading substances in this field, therefore they are labelled as first in class. Paired with the process of RNA interference, they enable selective gene silencing. Patisiran is used for treating hereditary transthyretin amyloidosis, givosiran for treating acute hepatic porphyria, lumasiran for treating primary hyperoxaluria type 1, and inclisiran for treating primary hypercholesterolemia as well as heterozygous familial and non-familial or mixed hypercholesterolemia. Due to eliminating numerous irregularities which occurred during treatments with antibodies, antisense oligonucleotides and pharmacological inhibitors, RNA interference offers a promising approach. This master’s thesis is the result of a critical overview of clinical studies, which studied the safety and efficacy of the above-mentioned substances. Combined with free online databases, MEDLINE was chosen as our main source of data collection. Basing on inclusion and exclusion criteria, we examined three studies of each patisiran, givosiran and lumasiran along with four studies of inclisiran, then showed the key features of the said studies in the tables. We summarised the data regarding the number of participants, the duration of each study, the dosage of the substances, and the primary results, then presented the results on their safety and efficacy. The efficacy of all four substances has been proven in the clinical studies. The positive effects of the medicines have been proven on the basis of the improved values of the set primary endpoints and laboratory values, which had been monitored during the studies. The results of the studies have shown the improvement of the patient’s disease or the cessation of its progression. Both the experimental and the control groups experienced similar frequencies of the medicines’ adverse effects, yet all the substances still displayed a favourable safety profile.
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