Spark Therapeutics' Gene Therapy Gets FDA Breakthrough Therapy Designation
By C. Rajan, contributing writer
Gene therapy company Spark Therapeutics has received the U.S. FDA’s coveted breakthrough therapy designation for its lead product candidate, SPK-RPE65, for the treatment of inherited blindness caused by mutations of the RPE65 gene.
The gene therapy product, SPK-RPE65, treats a family of vision-destroying genetic conditions called inherited retinal dystrophies (IRDs), which are caused by autosomal recessive mutations in the RPE65 gene. The breakthrough therapy designation was granted for one particular form of IRD, called nyctalopia (night blindness) in patients with a rare Leber's congenital amaurosis condition. There is currently no cure for this disease, which ultimately causes irreversible blindness.
"FDA's breakthrough therapy designation for SPK-RPE65 underscores the serious unmet medical needs faced by patients with genetic blinding conditions," said Jeffrey D. Marrazzo, co-founder and chief executive officer, Spark Therapeutics. "We look forward to working closely with FDA to facilitate the review of SPK-RPE65 as we work to bring this potentially transformative treatment to patients."
SPK-RPE65 is currently in a fully-enrolled pivotal Phase 3 clinical trial for the nyctalopia indication. Spark expects to report data from this Phase 3 trial in the second half of 2015 and hopes to file a Biologics License Application with FDA in 2016. The breakthrough therapy designation is provided to treatments for serious or life-threatening conditions, to help speed up the development of these therapies.
SPK-RPE65 was granted breakthrough therapy designation on the basis of promising results from two earlier clinical trials which demonstrated its potential to safely restore functional vision in patients with inherited retinal dystrophies (IRDs) due to the mutated RPE65 gene. The study also showed the long-lasting effects of SPK-RPE65 in restoring functional vision over a period of at least five years, as well as its abilities to help patients perform their normal daily activities more independently than they were able to before the treatment.
The clinical team also observed that a single injection of SPK-RPE65 in one eye allowed children in the trials who were almost completely blind, to be able to carry out classroom activities without visual aids, recognize faces, and behave more like normally sighted children.
A spin-out of the Children's Hospital of Philadelphia, Spark was launched in October 2013 to develop gene-based medicines for various debilitating conditions, including inherited blindness and hematologic and neurodegenerative disorders. The company has another gene therapy product candidate in a Phase 1/ 2 clinical trial for hemophilia B.
Gene therapy involves identifying a faulty or improperly functioning gene responsible for the disease, and replacing the faulty gene with a healthy copy or ‘knocking out’ the mutated gene, to help cure the condition. While increasing popular in research circles and new biotech companies, gene therapy is still in the investigational stage due to possible safety issues and is currently evaluated only for diseases with no cure.
According to Spark’s press release, the company’s unique gene therapy products use adeno-associated virus (AAV) vectors as the vehicles to deliver the healthy genes into targeted cells, as AAV is known to be safe and effective and has several advantages over other delivery methods.