Newswise — PHILADELPHIA, JULY 13, 2017 — Spark Therapeutics (NASDAQ: ONCE), a fully integrated gene therapy company dedicated to challenging the inevitability of genetic disease, today announced The Lancet, a highly ranked peer-reviewed journal, has published Phase 3 clinical trial data of voretigene neparvovec, an investigational, potential one-time gene therapy candidate for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal disease (IRD). In the trial, investigational voretigene neparvovec improved functional vision, light sensitivity and visual field in study participants with RPE65-mediated IRD. A natural history study has shown that people with this IRD eventually progress to complete blindness.

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 University of Iowa, who was a principal investigator for the Phase 3 trial. “The data show clinically meaningful and statistically significant improvements in ability to navigate independently in low to moderate light conditions, as well as marked improvements in full-field light sensitivity and peripheral vision. As a treating physician, it’s exciting to see these types of results in a disease area where no approved pharmacologic treatment options currently exist.

In May 2017, Spark Therapeutics completed the rolling submission of a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for voretigene neparvovec for the treatment of patients with vision loss due to confirmed biallelic RPE65 mutation-associated retinal disease. FDA has 60 days to review the submission to determine if it is complete. If deemed complete, the application will be considered filed and the review period will begin. Voretigene neparvovec has received breakthrough therapy designation from FDA, given to drugs when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies based on one or more clinically significant endpoints, and orphan product designations from FDA and European Medicines Agency (EMA), granted to drugs that treat a rare disease or condition.


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.


About Spark Therapeutics

Spark Therapeutics, a fully integrated company, strives to challenge the inevitability of genetic disease by discovering, developing, and delivering gene therapies that address inherited retinal diseases (IRDs), neurodegenerative diseases, as well as diseases that can be addressed by targeting the liver. Our validated platform successfully has delivered proof-of-concept data with investigational gene therapies in the retina and liver. Our most advanced investigational candidate, voretigene neparvovec, in development for the treatment of biallelic RPE65-mediated IRD, has received orphan designations in the U.S. and European Union, and breakthrough therapy designation in the U.S. The pipeline also includes SPK-7001 in a Phase 1/2 trial for choroideremia, and two hemophilia development programs: SPK-9001 (which also has received both breakthrough therapy and orphan product designations by the FDA, and access to the PRIority MEdicines (PRIME) Program by the EMA) in a Phase 1/2 trial for hemophilia B being developed in collaboration with Pfizer, and SPK-8011, in a Phase 1/2 trial for hemophilia A to which Spark Therapeutics retains global commercialization rights. To learn more about us and our growing pipeline, visit


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 FDA may not be accepted, or, if accepted, may not be approved; (ii) the data from our Phase 3 clinical trial of voretigene neparvovec may not support labeling for all biallelic RPE65 mutations other than Leber congenital amaurosis (LCA); and (iii) the improvements in functional vision demonstrated by voretigene neparvovec in our clinical trials may not be sustained over extended periods of time. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" section, as well as discussions of potential risks, uncertainties and other important factors, in our Annual Report on Form 10-K, our Quarterly Reports on Form 10-Q and other filings we make with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Spark undertakes no duty to update this information unless required by law.


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