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
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