First FDA-approved retinal gene therapy available at Mayo Clinic

Nov. 23, 2024

Gene therapy has the potential to treat previously incurable complex diseases. The first prescription retinal gene therapy product is now available at Mayo Clinic. For eligible patients who have a mutation in both copies of the RPE65 gene, voretigene neparvovec-rzyl is a one-time gene therapy that has the potential to restore the visual cycle and to improve functional vision.

With credentialed physicians to administer voretigene neparvovec-rzyl, Mayo Clinic now provides the first Food and Drug Administration (FDA)-approved gene therapy for people with an inherited retinal disease (IRD). "This is a game changer, not only for ophthalmology but also for all of medicine," says Brittni A. Scruggs, M.D., Ph.D., an ophthalmologist at Mayo Clinic in Rochester, Minnesota, who is trained in administering the therapy. "This treatment sets the stage for other gene therapies, and it's an exciting innovation to be a part of."

Voretigene neparvovec-rzyl is used to treat patients who have both of the following:

Leber congenital amaurosis due to mutations in both copies of the RPE65 gene.
Sufficient viable cells remaining in the outer retina, as determined by an IRD specialist.

If mutations are present in both copies of the RPE65 gene, patients can experience:

Night blindness, also known as nyctalopia.
Loss of contrast sensitivity or color vision.
Loss of central or peripheral vision.
Impaired dark adaptation.
Nystagmus.

Within the United States, a phase 3 clinical trial, published in The Lancet in 2017, showed that voretigene neparvovec-rzyl improved functional vision, which increased patients' ability to perform daily life activities. In this randomized, controlled trial performed at two U.S. sites, eligible participants included individuals with:

A confirmed genetic diagnosis of biallelic RPE65 mutation.
Sufficient viable retina.
Ability to perform standardized multiluminance mobility testing (MLMT) within the luminance range evaluated.

Participants were randomly assigned to intervention or control. It was found that vector administration in both eyes led to clinically meaningful and statistically significant improvements in the ability to navigate independently in low to moderate light conditions, as shown by change in MLMT score in the intervention group compared with that in controls.

"We inject voretigene neparvovec-rzyl under the retina, making a localized retinal detachment. This adeno-associated virus solution infects cells — specifically, the retinal pigment epithelium — that are still present but are not functioning," says Dr. Scruggs. "The virus works quickly, allowing the visual cycle to continue."

RPE65 is one of more than 300 genes that cause IRDs. Confirming a patient's specific gene mutation or mutations with a genetic test is the first step to determining whether this gene therapy is a relevant treatment option.

"Determining the exact genetic cause of a patient's disease allows our team to accurately make a diagnosis and counsel on prognosis, clinical trial opportunities and vision rehabilitation strategies," says Raymond Iezzi Jr., M.D., an ophthalmologist at Mayo Clinic in Minnesota who treats patients with IRDs.

At Mayo Clinic, highly skilled medical geneticists and board-certified genetic counselors meet with patients of all ages. Lisa A. Schimmenti, M.D., a board-certified clinical geneticist at Mayo Clinic, along with Mayo Clinic genetic counselors Kahlen R. Darr, M.S., CGC, and Lea M. Coon, M.S., CGC, provide timely, detailed and compassionate care.

"In a shared decision-making model, genetic testing is offered to individuals with suspected IRDs," says Dr. Schimmenti. "Our team gives individuals and families the knowledge needed to make informed decisions regarding genetic testing. Results are returned to individuals and families in the context of genetic counseling to understand the impact of their results and their eligibility for gene therapy."

"We've built an incredible collaboration with Mayo Clinic genetic consultants and counselors," says Raymond Iezzi Jr., M.D., an ophthalmologist at Mayo Clinic in Minnesota who treats patients with IRDs. "They see all patients with presumed IRDs within our ophthalmology clinic, where they provide consultations, talk through diagnoses, and work with patients and their families to make informed decisions."

Using state-of-the-art imaging modalities and collaborative relationships across Mayo Clinic, the Ophthalmology team has a breadth of resources available for each patient's unique needs.

Currently, clinical trials are ongoing in the following research areas:

Evaluating treatment for Stargardt disease.
Retinal dystrophies associated with rare disease-causing genetic variants.
Evaluating oral treatments in patients with retinitis pigmentosa.
Evaluating treatments for male participants with X-linked retinitis pigmentosa.

"Some patients with IRDs might not have a clinical trial or treatment as an option yet, and our priority is to optimize our patients' quality of vision and quality of life with the resources that we have," says Dr. Scruggs. "For patients who are candidates for voretigene neparvovec-rzyl, we're excited to be at the forefront of providing cutting-edge gene therapy — providing our patients a more vibrant view of the world."