Spark's gene therapy gets FDA breakthrough status

Spark Therapeutics has become the first company to get breakthrough status from the US Food and Drug Administration for a gene therapy.

The West Philadelphia company won the recognition for its lead product candidate SPK‐RPE65, a treatment for night blindness (nyctalopia) in patients with a genetic disorder called Leber congenital amaurosis.

The disease is one of a group called the inherited retinal dystrophies (IRDs) which prevent the eye responding normally to light and are a leading cause of blindness in children. It affects 2 to 3 per 100,000 newborns and has no pharmacological treatment available.

SPK-RPE65 is a genetic treatment designed to correct a defect in the RPE65 and is currently in a phase III trial which is due to report preliminary results next year. There are around 30 genes involved in Leber congenital amaurosis and RPE65 accounts for between 6 and 16 per cent of all cases of this condition.

The drug takes the form of an adeno-associated virus (AAV) vector that encapsulates a functional version of the mutated RPE65 gene and is injected directly into the eye as a one-off treatment.

Breakthrough designation will give SPK-RPE65 a speedy review and a higher level of interaction with the FDA once it is submitted for marketing. It has been awarded on the back of earlier studies which showed promising evidence of its ability to restore vision in patients affected by this disease.

The trials showed that patients treated with the gene therapy were able to perform activities of daily living with greater independence than prior to treatment, while the treatment had long‐lasting effects in restoring functional vision.

Early treatment seems to be best, with children who received a single injection of SPK-RPE65 in one eye no longer requiring visual aids to participate in classroom activities, and "ablt to walk and play more like normally-sighted children," according to the company.

"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," commented Spark chief executive Jeffrey Marrazzo.

Other companies working on gene therapies for eye diseases include Eyevensys - which is backed by Boehringer Ingelheim and is focusing initially on uveitis and age-related macular degeneration - and GenSight Biologics which is testing AAV-based therapies for Leber's hereditary optic neuropathy (LHON) and retinitis pigmentosa.

After decades of disappointment, gene therapy seems to be finally emerging as a viable treatment approach, passing a major milestone last year when Dutch biotech UniQure was granted approval for Glybera (alipogene tiparvovec), a treatment for patients with the inherited disease lipoprotein lipase deficiency (LPLD).

Some other gene therapies have been approved in emerging markets, including Shenzhen SiBiono Gene Technologies' Gendicine for head and neck cancer which is sold in China.