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Spark Therapeutics announces additional efficacy outcomes from first randomised US trial in gene therapy

Spark Therapeutics (NASDAQ:ONCE), a gene therapy company based in Philadelphia, USA, has announced additional efficacy results of the “first randomized, controlled phase 3 trial of a gene therapy for a genetic disease”. The company’s lead gene therapy product, termed “SPK-RPE65”, is a replacement gene therapy treatment for RPE65-mediated inherited retinal degeneration. The company had previously announced that the pivotal trial conducted in 31 patients met its primary endpoint (p = 0.001), indicating improvement of functional vision in the treated patients, compared to the control subjects, “as measured by the change in bilateral mobility testing between baseline and one year”. Following from their original announcement in October, new secondary endpoint data has been released at this year’s AAO meeting in Las Vegas indicating additional support from visual acuity measurements.


A presentation of the research findings from Principal Investigator, Albert M. Maguire, MD, Professor of Ophthalmology at the Perelman School of Medicine, University of Pennsylvania, showed that the eagerly awaited visual acuity outcomes provided further support of the ability for treated patients to navigate an obstacle course under varying light conditions. According to the secondary endpoint data, intervention subjects 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, compared with a “slight improvement” (1.6 letters) seen in control subjects. Approximately 30% of the treated patients (numbering seven of twenty) experienced a 15-letter, or three-line, improvement in the first eye administered, compared with no improvement in the control group. Finally, in the second eye administered, four of twenty treated patients achieved a 15-letter improvement, in comparison to no improvement seen in the control subjects.


In the study, the primary endpoint had involved assessing the patients’ performance in “navigating a mobility course under a number of varying light levels ranging from one lux (equivalent to a moonless summer night) to 400 lux (a brightly lit office)”. Each attempt of the course by a participant in the trial was recorded and, to ensure masking of treated subjects from controls, videos of the patients’ navigation attempts over a series of time points were sent to independent, centralized, masked graders who were tasked with assigning “a pass/fail score based on speed and accuracy with which the subjects navigated the course”. According to the trial results released by Spartk, the trial met its primary endpoint (p = 0.001) with no serious adverse events found and no deleterious immune responses detected in any of the trial subjects. Additional secondary endpoints that were successfully met included full-field light sensitivity threshold testing (p < 0.001) and a mobility test change score for the first injected eye (p = 0.001). Commenting on the additional visual acuity efficacy data, Dr. Maguire stated that, “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. 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.” It is understood that the company intends to apply for a marketing BLA with the US FDA at some point in FY2016.