The landscape of clinical trials research in inherited eye disease

Abstract

AbstractPurposeRecent increased understanding of molecular and genetic causes of many inherited eye diseases opens the way to novel therapeutic interventions. The key to drug discovery is in delivering precision targets for treatment that open a therapeutic index over toxicity. We set out to define what type of treatments are emerging, against what targets, and how the trial pipeline is progressing.MethodsWe selected 8 major inherited eye diseases where the primary genetic cause has been established, to identify potential therapeutic target. Data scrutiny and analysis of the clinical trials database on clinicaltrials.gov was performed from 20/3/2021 to 30/4/2021.ResultsWe identified 92 trials, of which 33 trials (35.9%) are ongoing or recruiting. Of these 92 trials, 44 trials (47.8%) are completed (but only 14 (31.8%) of these have posted results). 15 trials (16.3%) have an unknown status or are terminated. 52% of the trials are in North America, followed by 29% in Europe and 19% in other parts of the world. Drug intervention accounts for 44% of the trials and 20% are classified as biological intervention. Gene therapy accounts for 13% and 1% are combination intervention trials. Device intervention accounts for 9% with procedure intervention e.g., stem cell transplantation accounting for further 8%. The remaining 5% is classified as others intervention e.g. diet. Some of the trials are in more than 1 phases; 34 of the trials have phase 1 included, 37 trials have phase 2 included and only 10 trials have phase 3 included and this declines to only 1 trial with phase 4 included(a total decrease of 90%). Out of the 15 terminated or status unknown trials, 5 trials are in both phase 1 & 2, 3 trials are only in phase 1, 4 trials are only in phase 2 and 1 trial is only in phase 3. 2 trials are N/A due to device intervention. Combining the data, 8 trials with phase 1 testing included are terminated or with unknown status; 9 trials with phase 2 testing included are terminated or with unknown status. 1 trial with phase 3 testing included is terminated.ConclusionsCurrent and future clinical trials in the genetic eye diseases with molecular targets identified have a promising future but the pipeline of translation from phase 1, 2 trials to phase 3 is slow. Nevertheless, the last 5 years has seen a significant increase in therapeutic trials in inherited eye diseases.