The number and geographical distribution of clinical trials are important indicators of both the therapeutic viability and future potential of innovative pharmacological interventions. It is obvious that pharmaceutical / biopharmaceutical companies would invest in conducting extensive clinical studies for only those drug / therapy classes that are likely to translate into commercial success. Moreover, the geographical distribution directly indicates the various markets that are open to receiving / adopting the intervention(s) under investigation. As more product candidates get approved by regulatory authorities across the globe, the number of clinical trials across different global regions is anticipated to increase.
Close to 20% of the clinical trials for RNAi therapeutics have been / are being conducted for genetic disorders and oncology. It is followed by metabolic disorders (13%), ophthalmic disorders, infectious disorders and cardiovascular disorders each 8%. It is important to mention that majority of RNAi therapeutics being evaluated for infectious diseases are targeting hepatitis B and hepatitis C. It is worth mentioning that, Onpattro, the first marketed RNAi therapeutic (Alnylam Pharmaceuticals), is intended for the treatment of hTTR amyloidosis, which is a genetic disorder
Majority of the RNAi therapeutics being evaluated in phase I (22%) and phase II (26%) trials target oncological indications. On the other hand, most (41%) of the molecules being evaluated in phase III trial target genetic disorders. It is worth highlighting that 40% of phase III trials in Europe are evaluating RNAi therapeutics for the treatment of genetic disorders.
Most of the completed / ongoing / planned trials for RNAi therapeutics are centered in Europe. Further, within this region, UK (27) emerged as the most prominent center for the clinical trials related to RNAi therapeutics. Within North America, the maximum number of trials (70) were reported to be / have been conducted in US. In Asia, till September 2019, the maximum number of trials were registered in Australia (15), followed by India (8).
Maximum number of patients were enrolled in studies centered in Europe. Further, within Europe, most of the patients were enrolled in UK (16,508) for studies of RNAi therapeutics. In North America, the maximum number of patients were enrolled for RNAi therapeutics-based studies in the US (9,249). Within the Asia region, most of the patients were enrolled in studies based in Australia (387).
The below table highlights all the late-stage clinical trials (phase II/III phase III) for RNAi therapeutics that are expected to end (primary completion) in 2019 and 2020.
Type of RNAi Molecule
Target Patients Enrolled
Primary Completion Date
As can be observed from the table, a total of eight phase III clinical trials evaluating four drug candidates, using siRNA molecules, for the treatment of different indications are expected to complete in the coming two years. On the other hand, drugs based on miRNA, namely Cobomarsen (MRG-106) and Remlarsen (MRG-201), which are being developed by miRagen Therapeutics, are currently in phase II clinical trials likely to be completed by December 2021 and April 2020, respectively. In addition, vigil, a shRNA-based drug being developed by Gradalis, is currently in phase III, expected to be completed by July 2022. Further, BB-401, a DNA based drug being developed by Benitec Biopharma, is currently being evaluated in a phase II clinical trial which is likely to reach completion by April 2019.