FDA Approves Gene Therapy for Inherited Vision Loss

The FDA Wednesday approved Spark Therapeutics Inc.’s voretigene neparvovec-rzyl (Luxturna), the first gene therapy for inherited vision loss caused by faulty gene mutations.

Luxturna is approved for the treatment of both pediatric and adult patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy that leads to vision loss and may cause complete blindness in certain patients. Luxturna is the first directly administered gene therapy approved in the United States that targets a disease caused by mutations in a specific gene.

“Today’s approval marks another first in the field of gene therapy—both in how the therapy works and in expanding the use of gene therapy beyond the treatment of cancer to the treatment of vision loss—and this milestone reinforces the potential of this breakthrough approach in treating a wide-range of challenging diseases,” said FDA Commissioner Scott Gottlieb, MD, in a statement.

While a price for the treatment has not been announced, in a conference call with analysts last month announcing third-quarter results, the chief executive officer of the company said an expected price point may be about $1 million per patient, based on their estimate of what curing blindness might mean to both patients and families in terms of direct and indirect medical costs.

However, the Institute for Clinical an Economic Review (ICER), a Boston-based, non-profit drug-pricing watchdog, has released a draft evidence report on Luxterna that says $1 million is too high, and suggests a more cost-effective threshold, depending on the age treatment starts and the quality-adjusted life-year used, may be more in line with $231,134 to $573,200.

Hereditary retinal dystrophies are a group of genetic retinal disorders. They are caused by mutations in any one of more than 220 different genes. About 1000 to 2000 patients in the United States are affected. Carriers have a mutation (not necessarily the same mutation) in both copies of a particular gene (a paternal and a maternal mutation).

The RPE65 gene provides instructions for making an enzyme that is essential for normal vision. Mutations in the RPE65 gene lead to reduced or absent levels of RPE65 activity, resulting in impaired vision. Individuals see a progressive deterioration of vision over time, and may ultimately end in complete blindness.

Luxturna works by delivering a normal copy of the RPE65 gene directly to retinal cells. These retinal cells then produce the normal protein that converts light to an electrical signal in the retina to restore vision loss. Luxturna uses a naturally occurring adeno-associated virus, which has been modified using recombinant DNA techniques, as a vehicle to deliver the normal human RPE65 gene to the retinal cells to restore vision.

Luxturna should be given only to patients who have viable retinal cells. Treatment with Luxturna must be done separately in each eye on separate days, with at least 6 days between surgical procedures. It is given via subretinal injection by a surgeon experienced in performing intraocular surgery. Patients should be treated with a short course of oral prednisone to limit the potential immune reaction to Luxturna.

Spark plans to conduct a post-marketing observational study involving patients treated with Luxturna. The most common adverse reactions from treatment with Luxturna included eye redness (conjunctival hyperemia), cataract, increased intraocular pressure, and retinal tear.

The FDA granted this application priority peview and breakthrough therapy designations. Luxturna also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The company also received a rare pediatric disease priority review voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.