Spark Therapeutics' Revolutionary Gene Therapy for Blindness Faces the FDA on Thursday

Spark Therapeutics' Revolutionary Gene Therapy for Blindness Faces the FDA on Thursday
October 10, 2017
By Mark Terry, Breaking News Staff

Philadelphia – Thursday, Oct. 12, is a big day for Spark Therapeutics. The company’s Luxturna (voretigene neparvovec), a gene therapy for a rare, genetic form of blindness, will be reviewed by a U.S. Food and Drug Administration (FDA) panel.

In the company’s key study, 21 patients with retinal dystrophy caused by biallelic mutations in the RPE65 gene, were treated, with 10 in the placebo group. Of the 21 treated, 11 had significant improvement in light levels in both eyes. Fifteen of the patients scored a significant multi-luminance mobility testing (MLMT) improvement in the first eye treated.

John Carroll, writing for Endpoints News says, “Checking visual acuity, though, shows that the patients failed to demonstrate a significant improvement for the designated secondary, leaving Spark to seek a pioneering approval using an endpoint that’s never been used before in this way.”

Thursday’s internal panel will evaluate the significance of the endpoint, which is the impact the improvements have on patients’ daily activities, in addition to the impacts if the patients need more than a single treatment. Although the company believes the treatment is a one-shot, there’s no evidence how long the treatment will actually last.

The FDA review states, “There is no available long term follow up data to address whether the effect decays over time. Therefore, the duration of AAV2-mediated trans-gene expression leading to sustained clinical benefits beyond one year is unclear.”

The review also expressed concern over the company ignoring its advice over a co-primary endpoint—how the first eye treated was affected compared to both eyes. Since one eye can—and often does—compensate for vision impairment in the other eye, the FDA reviewers wanted to be able to tell if that was occurring, but the study didn’t take it into consideration.

Carroll writes, “None of that marks a kiss of death for this application. The reviewers are careful to avoid any harsh judgments or endorsements, staying neutral on the key questions regarding efficacy and safety. But it’s also not exactly the kind of discussion any gene therapy company wants to have.”

Anecdotally, at least, the patients treated with the therapy successfully have had dramatic changes in their lives. Leber congenital amaurosis (LCA) is caused by mutations in RPE65, which inhibits the production of a protein needed by the retina. Patients with LCA often see only a bright light, blurry shapes and eventually lose all vision.

Two of the patients in the trial, siblings Cole Carper, age 11, and Caroline Carper, age 13, were essentially blind prior to treatment.

After treatment, Cole told SFGate, “I looked up and said, ‘What are those light things?’ And my mom said, “Those are stars.’”

His sister, who was treated at the age of 10, told SFGate, that after treatment, “I saw snow falling and rain falling. I was completely surprised. I thought of water on the ground or snow on the ground. I never thought of it falling.”

“There were children who were able to move from a Braille classroom to a sighted classroom,” Katherine High, president of Spark, told SFGate. “One person who had never worked was able to get a job.”

Complications that were reported did not appear to be related to the gene therapy. One was caused by another drug given after therapy, and another was related to the surgical procedure itself.

Although the hearing is Thursday, a final decision will be made by Jan. 18, 2017. The recommendation for or against on Thursday is not binding, but the FDA definitely takes it into consideration.

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