Spark Therapeutics

Spark was founded about 2 years ago with the vision of building a fully integrated gene therapy company with research and development, manufacturing, and commercial divisions. The company is the brainchild of several researchers at Children’s Hospital of Philadelphia; at mid-year, Spark had $223 million on hand.

The goal of Spark’s development is “one-time, potentially life-altering treatments for genetic diseases, specifically with a focus on blindness, hemophilia, neurodegenerative diseases,” Mr. Marrazzo said. Spark is working with Pfizer in hemophilia B treatments and developing its own hemophilia A treatment. It recently announced a program for Batten’s disease, a pediatric onset neurodegenerative disorder that causes early childhood death.

Spark has begun a phase III study for 31 patients with RPE65 mutations (clinically referred to as Leber’s congenital amaurosis). The SPK-RPE65 study was designed with a 2:1 randomization. Two-thirds of the subjects were randomized to receive one single injection in each eye. Control group eyes were allowed crossover. Primary outcomes were a change in a mobility test score at 1 year, since a hallmark of LCA is night blindness. Clinically meaningful improvement would include someone’s ability to navigate the course successfully under darker and darker lighting conditions. Topline results showed statistically significant improvements (P=.001) for the primary and secondary outcomes. Results indicated 65% of subjects were able to pass the mobility test at the lowest lux level; there was a 100-fold improvement in light sensitivity. Following subjects from the phase 1 study (now at 3 years) has shown the gains achieved at 30-90 days are consistent through year 3.

There were no serious adverse events related to the product during any of the trials.

SPK-RPE65 is the first-ever randomized clinical study for gene therapy that has shown success. The therapy has received orphan product designation in the European Union and the U.S. for LCA and retinitis pigmentosa due to RPE65 mutations. Payor dialogues are under way and a BLA submission is planned for 2016.

Spark has begun a phase I/II study on SPK-CHM for the treatment of choroideremia, a disease that affects 3-4 times the number of people as are affected by RPE65 mutations. RhoNova addresses RHO-adRP and uses a novel dual-vector gene therapy strategy to suppress the mutant rhodopsin gene and to replace it with a normal gene resistant to the suppressor.

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