Spark Therapeutics Announces Presentation of Additional Phase 3 and Durability Data on SPK-RPE65 at The Retina Society 48th Annual Scientific Meeting

Rapid and Sustained Difference Observed Between Intervention and Control Subjects Across Multiple Parameters Throughout Entire Phase 3 Study Period

Durable Effect Seen Over Three Years, With Observation Ongoing, in Functional Vision and Light Sensitivity in Phase 1 Trial

PARISOct. 10, 2015 (GLOBE NEWSWIRE) -- Spark Therapeutics, Inc. (NASDAQ:ONCE) announced today the presentation of additional data from the Phase 3 pivotal trial as well as continued durability data from an earlier Phase 1 study of SPK-RPE65, its lead product candidate for the treatment of RPE65-mediated inherited retinal dystrophies (IRDs).  

Principal Investigator Stephen R. Russell, MD, of the Stephen A. Wynn Institute for Vision Research at the University of Iowa, presented Phase 3 data highlighting the rate, breadth and magnitude of changes seen across the primary endpoint and first secondary endpoint following administration of SPK-RPE65. In addition, Dr. Russell presented data on the three-year durability of improvements in the same measures of functional vision and light sensitivity in a cohort of subjects from an earlier Phase 1 trial.

Today's presentation builds on top-line results of a randomized controlled multi-center Phase 3 trial announced by Spark on October 5, which demonstrated a highly statistically significant improvement in the intervention group compared to the control group in the primary endpoint and two of three secondary endpoints. There were no serious adverse events related to SPK-RPE65 in the Phase 3 trial.

Significant Improvements and Strong Parallels in Mobility and Light Sensitivity Testing

Data presented today highlighted a mean improvement in the functional vision of intervention subjects (n=20) of 1.9 specified lux levels, compared with an improvement of 0.2 specified lux levels in control subjects (n=9) as measured by the change in bilateral mobility testing (MT) between baseline and one year in the modified intent-to-treat (mITT) population. The mITT population (n=29) includes all subjects that received SPK-RPR65, and only those who continued beyond the baseline study visit. Two subjects in the intent-to-treat (ITT) population (n=31) that were randomized but never received SPK-RPE65 are excluded from this efficacy analysis population. Thirteen of the 20 subjects receivingSPK-RPE65 were able to pass the MT at one lux at year one, demonstrating maximum improvement measurable on the MT score. None of the nine control subjects followed was able to pass MT at one lux at year one.

In a corresponding finding in the first secondary efficacy endpoint, full-field light sensitivity threshold testing (FST) for white light, intervention subjects demonstrated a highly statistically significant mean improvement of -2.06 log10(candela second/m2) compared with decline of 0.04 log10 (candela second/m2) among control subjects (all analyses in mITT population).

"It's exciting to see a consistency of improvement between the functional vision and visual function. The parallel effect seen in the prompt response in both the primary and first secondary endpoints highlights a critically important finding from the trial: that functional improvements measured through the mobility test change score correspond closely with the physiologic impact seen through FST," Dr. Russell said.

Rapid and Sustained Effect Demonstrated in Phase 3 Trial

Dr. Russell presented additional top-line analyses from the pivotal Phase 3 trial showing the rapid and sustained impact of SPK-RPE65 throughout the entire one-year study period. Significant differences emerged in both MT and FST by the first study visit, at 30 days. These effects were reproduced consistently at each subsequent study visit (at days 90, 180 and one year).

Phase 3 Trial of SPK-RPE65: MT and FST Over Time (mITT)

Durable Response Continuing through Three Years in Comparable Cohort from Earlier Phase 1 Study

Dr. Russell also presented data on the durability of effect after three years as measured by MT and FST in a cohort of subjects that participated in the Phase 1 open-label 102 study, and would likely have met the eligibility criteria for the Phase 3 trial. All of these subjects continue to experience a durable improvement over three years from the time of administration to the contralateral, or second eye, with observation ongoing. These subjects received the same dose and volume of SPK-RPE65 that was used in the pivotal Phase 3 trial. The figures below reflect data from all subjects available for follow-up at each time point reported. Spark and the clinical investigators continue to follow study participants to evaluate the durability of response, and will provide further updates in the future through a series of peer-reviewed presentations and publications.

Phase 1 Trial of SPK-RPE65: Durability of MT and FST Over Time (102-injected eye)

"We are pleased to provide these additional informative data, the totality of which highlight the rapid, sustained and durable effect associated with SPK-RPE65 across multiple functional and physiological parameters, at time points ranging from 30 days to three years," said Jeffrey D. Marrazzo, co-founder and chief executive officer of Spark. "We will continue to analyze the data from our groundbreaking pivotal Phase 3 trial in order to further elucidate the potential positive, meaningful impact that SPK-RPE65 can have on the lives of patients with RPE65-mediated blinding conditions."

Principal Investigator Albert Maguire, MD, professor of ophthalmology at the Perelman School of Medicine of theUniversity of Pennsylvania, will present additional data about SPK-RPE65 during the American Academy of Ophthalmology Retina Sub-specialty meeting on November 14th in Las Vegas, NV.

Pivotal, Phase 3 Trial Overview

The pivotal Phase 3 trial of SPK-RPE65 is the first successful randomized, controlled Phase 3 trial ever completed in gene therapy for a genetic disease. The multicenter trial randomized 31 subjects with confirmed RPE65 gene mutations. The ITT population included 21 subjects in the intervention group and 10 in the control group.

For the primary endpoint, subjects were evaluated at multiple time points over the course of one year for their performance in navigating a mobility course under a variety of specified light levels ranging from one lux (equivalent to a moonless summer night) to 400 lux (a brightly lit office) using the bilateral testing condition. Each attempt was recorded, and the videos were sent to independent, centralized, masked graders to assign a pass/fail score based on speed and accuracy with which the subjects navigated the course.

In addition to the primary endpoint, the statistical analysis plan included three secondary endpoints tested statistically in the following hierarchical order:

  • FST (white light), which reflects underlying physiological function by measuring light sensitivity of the entire visual field.
  • Change in MT score for the assigned first eye, which compares the MT performance between baseline and year one for the first eye injected for the intervention group and, for the control group during the control year, the first eye injected after they crossed over.
  • Visual acuity (VA) testing, which measures changes in central vision by assessing the ability of the subject to read a standard eye chart.

A summary of top-line efficacy results follows:

Primary outcome (ITT)  
MT change score, bilateral  p = 0.001
Secondary outcomes (ITT)  
FST, averaged over both eyes  p < 0.001
MT change score, first injected eye  p = 0.001
VA, averaged over both eyes p = 0.17

About Spark Therapeutics

Spark is a gene therapy leader seeking to transform the lives of patients with debilitating genetic diseases by developing one-time, life-altering treatments. Spark's initial focus is on treating rare diseases where no, or only palliative, therapies exist. Spark's most advanced product candidate, SPK-RPE65, which has received both breakthrough therapy and orphan product designation, recently reported positive top-line results from a pivotal Phase 3 clinical trial for the treatment of rare blinding conditions. Spark's validated gene therapy platform is being applied to a range of clinical and preclinical programs addressing serious genetic diseases, including inherited retinal dystrophies, hematologic disorders and neurodegenerative diseases. Spark builds on two decades of research, development and manufacturing at The Children's Hospital of Philadelphia, including human trials conducted across diverse therapeutic areas and routes of administration. To learn more, please 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 lead product candidate, SPK-RPE65. 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) the data from our Phase 3 clinical trial of SPK-RPE65 may not support a label for the treatment of RPE65-mediated IRDs other than Leber congenital amaurosis (LCA); and (ii) the improvements in functional vision demonstrated by SPK- RPE65 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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