Gyroscope also announced that the U.S. Food and Drug Administration (FDA) has granted a second Fast Track designation to GT005. The new Fast Track designation is for the treatment of GA in people with variants in their complement genes. Approximately 95% of people with GA carry at least one genetic variant in a complement gene.[i] This patient population is being evaluated in the Phase II HORIZON trial. Gyroscope estimates that nearly 3.5 million people in the United States and EU5 European countries have GA.[ii],[iii]
“We are excited to get the HORIZON trial underway. We have designed a robust clinical development programme with two randomized controlled Phase II trials evaluating the safety and effectiveness of GT005 in two different populations of people with GA. These include a specific genetically defined subset of people with GA, as well as a broader group of GA patients. Ultimately, these two trials along with our Phase I/II FOCUS trial will enrol approximately 300 patients,” said Nadia Waheed, M.D., MPH, Chief Medical Officer. “We are also very pleased to receive a second Fast Track designation from the FDA for GT005. We look forward to continuing to work with the FDA as we advance our clinical programme with the goal of bringing a treatment option to the millions of people with GA.”
The FDA Fast Track programme streamlines the review of drugs for serious conditions without FDA-approved treatment options available. Fast Track designation gives applicants access to more frequent communication with the FDA throughout the review process. It also provides the potential to apply for Accelerated Approval and Priority Review if relevant criteria are met, as well as Rolling Review, which means that completed sections of the Biologic License Application can be submitted for review before the entire FDA application is complete.
About the GT005 Clinical Programme
The GT005 clinical programme consists of three clinical trials.
FOCUS [NCT03846193] is a Phase I/II open-label clinical trial that was initiated in January 2019. The trial is evaluating the safety and dose response of GT005 in people with GA secondary to dry AMD. Three doses of GT005 are being evaluated in FOCUS. The dose escalation phase of FOCUS is complete and the trial is now enrolling additional cohorts. Gyroscope plans to enrol approximately 45 people who have a clinical diagnosis of GA secondary to dry AMD in FOCUS at sites in the United Kingdom and United States.
HORIZON [NCT04566445] and EXPLORE [NCT04437368] are Phase II, multicentre, randomised, controlled trials evaluating the safety and effectiveness of GT005 administered as a single subretinal injection. The primary endpoint for both trials is progression of GA over 48 weeks. The trials will also evaluate GT005 for various safety and tolerability measures. Participants in both trials may be assigned to one of two treatment arms (two GT005 doses are being evaluated in each trial) or an untreated control arm and will be followed for 48 weeks. All participants enrolling in EXPLORE and HORIZON will be genotyped.
HORIZON is enrolling approximately 180 people with GA secondary to dry AMD who have variants in their complement genes. Participants in HORIZON will be stratified by AMD genotype subgroup.
EXPLORE is enrolling approximately 75 people with GA secondary to dry AMD who have rare variants in their CFI gene and low levels of the CFI protein in their blood. In September 2020, the FDA granted Fast Track designation to GT005 for the treatment of the population being evaluated in the Phase II EXPLORE trial. Gyroscope estimates there are more than 100,000 people with GA in the United States and EU5 European countries who have these rare CFI variants.1,2,3,[iv]
EXPLORE and HORIZON are enrolling patients at sites based in the United States, Europe and Australia.
Gyroscope’s lead investigational gene therapy, GT005, is a one-time therapy delivered under the retina. An overactive complement system has been implicated in the development of AMD. GT005 is designed to restore balance to an overactive complement system, a part of the immune system, by increasing production of the CFI protein. The CFI protein regulates the activity of the complement system. It is believed that increasing CFI production will dampen the system’s overactivity and reduce inflammation, with the goal of preserving a person’s eyesight.
About Dry Age-Related Macular Degeneration (AMD) and Geographic Atrophy (GA)
Dry AMD is a leading cause of permanent vision loss in people over the age of 50 and is a devastating diagnosis.[v] There are currently no approved treatments for dry AMD, which is the most common form, impacting approximately 90% of people with AMD.[vi] As dry AMD advances it leads to GA, an irreversible degeneration of retinal cells, causing a gradual and permanent loss of central vision. This disease can severely impact a person’s daily life as they lose the ability to drive, read and even see the faces of loved ones.
About Gyroscope: Vision for Life
Gyroscope Therapeutics is a clinical-stage retinal gene therapy company developing gene therapy beyond rare disease to treat a leading cause of blindness, dry AMD. Our lead investigational gene therapy, GT005, is a one-time therapy delivered under the retina. GT005 is designed to restore balance to an overactive complement system by increasing production of the Complement Factor I protein. GT005 is currently being evaluated in a Phase I/II clinical trial called FOCUS and Phase II clinical trials called EXPLORE and HORIZON.
Syncona Ltd, our lead investor, helped us create the only retinal gene therapy company to combine discovery, research, drug development, a manufacturing platform and surgical delivery capabilities. Headquartered in London with locations in Philadelphia and San Francisco, our mission is to preserve sight and fight the devastating impact of blindness. For more information visit: www.gyroscopetx.com and follow us on Twitter (@GyroscopeTx) and on LinkedIn.
[i] Data on File.
[ii] Friedman DS, O’Colmain BJ, Muñoz B, et al. Prevalence of age-related macular degeneration in the United States [published correction appears in Arch Ophthalmol. 2011 Sep;129(9):1188]. Arch Ophthalmol. 2004;122(4):564-572.
[iii] Rudnicka AR, Kapetanakis VV et al. Incidence of late-stage age-related macular degeneration in American whites: systematic review and meta-analysis. Am J Ophthalmol. 2015;160:85-93.
[iv] Kavanagh D, Yu Y, Schramm EC, et al. Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels. Hum Mol Genet. 2015;24(13):3861-3870.
[v] National Eye Institute. Age-Related Macular Degeneration. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration. Accessed July 16, 2020.
[vi] Centers for Disease Control and Prevention. Age-Related Macular Degeneration. https://www.cdc.gov/visionhealth/basics/ced/. Page last reviewed June 3, 2020. Accessed August 4, 2020.