Spark Therapeutics' Gene Therapy Yields Results for Improving Blindness

The Philadelphia based Spark Therapeutics ( ONCE ) announced earlier today the company's gene therapy product SPK-RPE65 has shown "positive top-line results from the Phase 3 pivotal trial…for the treatment of RPE65-mediated inherited retinal dystrophies (IRDs)."

This trial testing for the company's therapy met its "primary endpoint (p = 0.001), demonstrating improvement of functional vision in the intervention group compared to the control group, as measured by the change in bilateral mobility testing between baseline and one year."

As a result of this news, the Zacks Rank #3 (Hold) company has been trading up on the day - currently trading 25% higher.

The Results

Below is a summary of the results the company has released:

Primary outcome (ITT)

  • Mobility test (MT) change score, bilateral - p = 0.001

Secondary outcomes (ITT)

  • FST, averaged over both eyes - p
  • MT change score, first injected eye - p = 0.001
  • Visual acuity, averaged over both eyes - p = 0.17

The 'p' value, in any form of statistical analysis, measures how statistically significant variables are when measuring the effect they have on a dependent variable. P = 0.05 is widely accepted in the scientific community as the starting point for variables to be statically significant. Variables with p values of 0.05 or lower are considered statistically significant.

Another interpretation to p = 0.05 is that an individual can predict with 95% confidence that there is a relationship between the variables tested, in turn rejecting the null hypothesis (no relationship between data sets).

Spark Therapeutics does not define what its confidence threshold was for the testing. However, Spark Therapeutics does write the following: "In addition, subjects who received SPK-RPE65 outperformed control subjects across the first two secondary endpoints: full-field light sensitivity threshold testing (p

The company continues by stating, "The third secondary endpoint, visual acuity, did not show statistically significant evidence of benefit (p = 0.17). All reported p-values reflect results from the intent-to-treat (ITT) population, the most stringent efficacy analysis population described in the statistical analysis plan (SAP)."

To translate, the 'p' values for the first 3 outcomes are less than 0.05 and therefore, the null hypothesis can be rejected with both 95% and 99% confidence. The 'p' value for visual activity, on the contrary, is more than 0.05 (0.17) and therefore, the results of the testing are not statistically significant - the null hypothesis cannot be rejected with 95% confidence.

The Testing

Unfortunately, the magnitude of these results were not release by Spark, therefore, we cannot determine how effective SPK-RPE65 is. Here is what has been released by the company about how the therapy performed:

"We saw substantial restoration of vision in patients who were progressing toward complete blindness," said Albert M. Maguire, MD, principal investigator in the trial and professor of ophthalmology at the Perelman School of Medicine of the University of Pennsylvania. "The majority of the subjects given SPK-RPE65 derived the maximum possible benefit that we could measure on the primary visual function test, and this impressive effect was confirmed by a parallel improvement in retinal sensitivity. If approved, SPK-RPE65 should have a positive, meaningful impact on the lives of patients with this debilitating condition."

"These results are the culmination of more than a decade of work of many dedicated individuals to correct the underlying cause of RPE65-mediated blindness through the one-time administration of a gene therapy," said Jean Bennett, MD, PhD, professor of ophthalmology and director of the Center for Advanced Retinal and Ocular Therapeutics at the Perelman School of Medicine of the University of Pennsylvania. "We are excited about the potential impact that the results will have on the treatment of this and other blinding conditions."

The testing and trial was conducted over the course of 1 year. The Phase 3 trial randomly selected 31 subjects with confirmed RPE65 gene mutations. The control group consisted of 10 individuals without the mutation and the "ITT population included 21 subjects in the intervention group."

During this year, the subjects were evaluated on their "performance in navigating a mobility course under a variety of light levels ranging from one lux (equivalent to a moonless summer night) to 400 lux (a brightly lit office) using the bilateral testing condition."

The secondary testing followed this hierarchical order:

  • Full-field light sensitivity threshold testing (FST), which reflects underlying physiological function by measuring light sensitivity of the entire visual field.
  • Change in mobility test score for the first eye injected, which compares the mobility test 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 testing, which measures changes in central vision by assessing the ability of the subject to read a standard eye chart.

Final Thoughts

Any statistically significant result that favors a way to correct a genetic blinding condition is always a good thing. Spark Therapeutics will file a Biologics License Application with the US Food and Drug Administration in 2016 based on their findings.

This was the first successful randomized and controlled Phase 3 trial ever completed in gene therapy for a genetic disease. Let's hope this trend continues.

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The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

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