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Functional vision refers to a person's ability to perform, on his or her own, visually dependent activities of daily living. This is typically measured per person rather than per eye, and may be thought of as the performance output of various aspects of visual function. Visual function is measured by tests performed on each eye individually, such as light sensitivity, visual acuity (determined by the smallest letters one can read on a standardized eye chart from a specified distance), and visual field (which refers to the area in which objects can be detected in the periphery while the eye is focused on a central point). This clinical trial evaluated both functional vision and various aspects of visual function.
The publication presents the results of the Phase 3 trial, including the intent-to-treat population of all randomized subjects, through the one-year timepoint. Results showed a statistically significant and clinically meaningful difference between intervention (n=21) and control participants (n=10) at one year, per the clinical trial's primary endpoint, mean bilateral multi-luminance mobility testing (MLMT) change score (difference of 1.6; 95% CI, 0.72, 2.41; p=0.0013). Participants maintained functional gains observed 30 days post-administration at the one-year primary endpoint. MLMT evaluates functional vision by documenting the participants' ability to navigate a mobility course under a variety of specified light levels ranging from one lux (equivalent to, for example, a moonless summer night) to 400 lux (equivalent to, for example, an office environment).
Improvements seen in MLMT were accompanied by statistically significant improvements in two secondary endpoints, including full-field light sensitivity threshold (FST) testing averaged over both eyes (p=0.0004). A third secondary endpoint, the change in visual acuity averaged over both eyes, was not statistically significant between intervention and control participants (p=0.17). An additional protocol-specified endpoint using the Goldmann III4e test stimulus to measure the visual field area of the original intervention group showed significant improvement (p=0.0059), nearly doubling at year one, while a slight decrease was observed in the control group over the same time period.
No serious adverse events (SAEs) associated with voretigene neparvovec or deleterious immune responses were observed. Most ocular events were mild in severity with the most common ocular adverse events (AEs) being transient mild ocular inflammation, transient elevated intraocular pressure, cataracts and intraoperative retinal tears. Two participants in the intervention group, one with a pre-existing complex seizure disorder and another who experienced complications from oral surgery, had SAEs unrelated to study participation.
Please refer to the paper, "Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in subjects with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label Phase 3 trial," for additional results from the pivotal phase of this study.
"These data from the first randomized, controlled Phase 3 gene therapy clinical trial ever conducted for a genetic disease are supportive of the potential role that investigational voretigene neparvovec may play in the treatment of IRD caused by biallelic mutations in the RPE65 gene," said Stephen R. Russell, M.D., of the Stephen A. Wynn Institute for Vision Research at the
About RPE65-mediated Inherited Retinal Disease (IRD)
Inherited retinal diseases (also known as inherited retinal dystrophies) are a group of rare blinding conditions caused by one of more than 220 different genes. People living with IRD due to biallelic RPE65 gene mutations often experience night blindness (nyctalopia) due to decreased light sensitivity in childhood or early adulthood and involuntary back-and-forth eye movements (nystagmus). As the disease progresses, individuals may experience loss in their peripheral vision, developing tunnel vision, and eventually, they may lose their central vision as well, resulting in total blindness. Independent navigation becomes severely limited, and vision-dependent activities of daily living are impaired. There are currently no approved pharmacologic treatment options for this disease.
About Gene Therapy
Gene therapy is an investigational approach to treat or prevent genetic disease by seeking to augment, replace or suppress one or more mutated genes with functional copies. It addresses the root cause of an inherited disease by enabling the body to produce a protein or proteins necessary to restore health or to stop making a harmful protein or proteins, with the potential of bringing back function in the diseased cells and slowing disease progression. To deliver the functional gene into the cell, a vector is used to transport the desired gene and is delivered either intravenously (IV) or injected into specific tissue. The goal is to enable, through the one-time administration of gene therapy, a lasting therapeutic effect.
Cautionary note on forward-looking statements
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the company's product candidates, including voretigene neparvovec, SPK-7001, SPK-9001 and SPK-8011. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that: (i) our BLA submitted to the
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