Inherited Retinal Disease

Regulatory Hurdles and Triumphs: One approved, many more on the horizon for ophthalmic gene therapies

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A significant number of gene therapy clinical trials have been conducted worldwide to treat ophthalmic disorders. A new study reveals key insights, such as the prevalence of Phase 1/2 trials, the dominance of the United States as a host for these trials, the focus on retina and optic nerve disorders, and the diverse methods employed, with gene augmentation using viral vectors being the most common.

Despite the substantial progress, the article emphasizes that regulatory approval has been achieved for only one trial so far, highlighting both the promising potential and the challenges associated with bringing gene therapies for eye conditions to market.

As of 2022, a total of 159 gene therapy clinical trials focused on ophthalmic diseases were identified. The distribution across trial phases demonstrated that Phase 1/2 trials held the highest frequency at 50.32%, closely followed by Phase 2 trials at 33.21%. Interestingly, a substantial portion of these trials—107 (67%)—were conducted within a single country, while 50 trials (31%) were multinational in scope.

The United States emerged as a prominent hub for these trials, hosting 113 (71%) of the total single or multinational trials. This underscores the global leadership and collaborative efforts within the U.S. in advancing gene therapy research for ophthalmic disorders.

Of the identified trials, 96% (153 trials) targeted retina and optic nerve disorders. Other conditions included glaucoma (2%), uveitis (1%), and cornea-related disorders (1%). Gene augmentation using viral vectors was the predominant method employed in 65% of the trials, with adeno-associated virus being the preferred transgene delivery mechanism in 87% of gene augmentation cases.

The study further revealed that most gene augmentation trials focused on addressing inherited retinal disorders (74%) and age-related macular degeneration, both wet (14%) and dry (7%). In addition, alternative methods such as inhibitory RNA (11%) and cell-based gene therapy using encapsulated cell technology (11%) were employed in a significant proportion of trials.

Despite the progress and widespread efforts in the field of gene therapy for ophthalmic disorders, regulatory approval has only been granted for 1 trial thus far. The findings underscore the complexity of bringing gene therapies to market but also highlight the tremendous potential these interventions hold for revolutionizing the treatment landscape of various eye conditions.

Ameri H, Kesavamoorthy N, Bruce DN. Frequency and Pattern of Worldwide Ocular Gene Therapy Clinical Trials up to 2022. Biomedicines. 2023;11(12):3124. doi: 10.3390/biomedicines11123124. PMID: 38137345; PMCID: PMC10740821.