Spark Therapeutics Announces Presentation of Additional Phase 3 Data on SPK-RPE65 at The American Academy of Ophthalmology 2015 Annual Meeting

Spark Therapeutics, Inc. ONCE announced today that additional secondary endpoint data from the Phase 3 pivotal trial of SPK-RPE65 were presented at the American Academy of Ophthalmology (AAO) 2015 Annual Meeting. SPK-RPE65 is Spark's lead product candidate for the treatment of RPE65-mediated inherited retinal dystrophies. As previously announced, the randomized controlled multicenter Phase 3 trial demonstrated a highly statistically significant improvement in the intervention group compared to the control group in the primary endpoint, the change in bilateral mobility testing (MT) between baseline and one year. The first two secondary endpoints -- full-field light sensitivity threshold testing (FST) and MT for the assigned first eye -- also showed highly statistically significant improvement. Principal Investigator Albert M. Maguire, MD, professor of ophthalmology at the Perelman School of Medicine of the University of Pennsylvania, presented a comprehensive overview of results at AAO, including new detail highlighting the positive trends seen in the third secondary endpoint, visual acuity. These data showed that intervention subjects in the modified intent-to-treat efficacy analysis population achieved a mean improvement of approximately two lines (9.0 letters averaged across both eyes) on the logarithm of the minimum angle of resolution (logMAR) scale, a standard measure of visual acuity, compared with a slight improvement (1.6 letters) among control subjects. Over one-third of the intervention subjects (seven of 20) saw a 15-letter, or three-line, improvement in the first eye administered, compared with none in the control group. In the second eye administered, four of 20 intervention subjects reached a 15-letter improvement compared with none of the control subjects. Spark continues to conduct analyses of the changes seen in visual acuity. "In addition to highly statistically significant results seen in the primary and first two secondary endpoints, it is also encouraging to see the positive trends in visual acuity, which measures a person's central vision," Dr. Maguire said. "The main effect of SPK-RPE65 involves rod-mediated photoreceptor function, which is why functional vision at different light levels is the most appropriate primary outcome measure. To also see a positive trend in visual acuity, which is primarily a function of foveal, cone-mediated function, is a positive finding." 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 previously announced 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, assigned first eye p = 0.001