- Novel gene therapy LUXTURNA™
(voretigene neparvovec-ryzl) was approved by
FDA for patients with confirmed biallelic RPE65 mutation-associated
- Approval of gene therapy for
inherited blindness may guide and give the much needed thrust and
understanding to develop similar treatments for other inherited disorders.
therapy for inherited retinal blindness has been approved by the FDA in
December 2017 in a historic move marking the first ever approval for gene
therapy for a genetic disease in the US. The treatment involves injecting the
corrective gene directly into the patient. The method has been pioneered by scientists at the
University of Pennsylvania and Children's Hospital of Philadelphia (CHOP).
approval follows nearly a 25 year research on congenital blindness by Jean
Bennett, MD, PhD
and Albert M. Maguire, MD
, a professor of
Ophthalmology at the Perelman School of Medicine.
‘Approval of gene therapy for retinal blindness may pave the way for development of treatments for other disabling genetic disorders such as hemophilia and sickle cell anemia.’
"I've witnessed the dramatic changes in the vision of
patients who would have otherwise lost their sight, and feel exhilarated that this therapy will now make a difference in the lives of more children and adults," Bennett said.
"I'm hopeful that the path we've made with this research, with the help of our collaborators near and far, will be useful to other groups, so that other gene therapies can be developed faster and help more people with other diseases."
Interestingly,this is the second FDA approval for a
University of Pennsylvania/CHOP-developed gene therapy in
. In August 2017, the personalized cellular therapy known as Kymriah™
was formally approved to treat advanced acute lymphoblastic leukemia in children and young adults.
Gene Therapy for Retinal
Blindness - A Boon to Sufferers
retinal dystrophies refer to a broad group of inherited retinal disorders
associated with progressive loss of vision, caused by mutations in any one of more than 220 different genes.
Bi-allelic RPE65 mutation-associated retinal dystrophy affects around 1,000 to 2,000 patients in the U.S. The RPE65 gene encodes for a protein that is essential for normal vision. Mutations in this RPE65
gene lead to reduced or absent levels of RPE65 protein activity
, affecting the visual cycle and resulting in impaired vision.
Children with the gene mutation often are diagnosed at an early age with disorders such as Leber congenital amaurosis (LCA) or retinitis pigmentosa. Affected individuals experience progressive loss of vision
over time. This loss of vision, seen typically during childhood or adolescence, ultimately progresses to complete blindness
Details of the LUXTURNA
Clinical Trial and Key Findings
this trial, corrected versions of the RPE65
gene was delivered
as a one-time injection, using a genetically engineered, benign adeno-associated
virus into the retina.
- The initial Phase 1/2 clinical
studies at University of Pennsylvania began in late 2007, with a total of
12 patients ranging from eight to 46 years old diagnosed with the disease.
- Within weeks of receiving the injections, most of them had improved
vision; in fact half of them had improvements to the degree they were
no longer considered legally blind.
- The Phase III trial included 29
patients aged 4 to 44 years and some of them were treated at the
University of Iowa.
- Results of the phase III trial
showed improved ability to navigate
in low light, increased sensitivity to light and better side vision.
- Many of the volunteers are now able to recognize faces, read
chalkboard, do grocery shopping, take driving tests, and have
more job opportunities, all of which seemed an impossible dream earlier.
date, 41 participants have received
therapy through the Universities of Pennsylvania and Iowa.
- The safety of the procedure was
comparable to vitrectomy operation and subretinal
- Adverse effects included cataract,
intraocular infection, reduced visual acuity (one patient), altered
intraocular pressure and macular changes.
Precautions to Take
While Giving LUXTURNA
- Luxturna should be administered only
to patients who have viable retinal cells as determined by the treating
- Luxturna therapy must be done
separately in each eye on separate days, with a minimum six-day
gap between the procedures.
- It is given via subretinal injection
by a surgeon skilled in intraocular surgery.
- Patients treated with Luxturna
should also receive a short course of oral prednisone to limit the
potential immune reaction to Luxturna.
approval of Luxturna further opens the door to the potential of gene
therapies," said Peter Marks, M.D., Ph.D., director of the FDA's Center for
Biologics Evaluation and Research (CBER). "Patients with biallelic RPE65
mutation-associated retinal dystrophy now have a chance for improved vision,
where little hope previously existed."
Further Plans for the
- To further evaluate the long-term safety, the manufacturer (Spark
Therapeutics Inc) and the research team plan to perform a post-marketing
observational study involving patients treated with Luxturna.
- FDA plans next year (2018) to begin issuing a series of disease-specific
guidance documents on the development of specific gene therapy agents
using modern and more efficient parameters and clinical measures in order
to evaluate and review of gene therapy for various high-priority disorders
that are currently being trialed.
- FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss - (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm589467.htm)
- FDA Approves Gene Therapy for Inherited Blindness Developed by the University of Pennsylvania and Children's Hospital of Philadelphia - (https://www.pennmedicine.org/news/news-releases/2017/december/fda-approves-gene-therapy-for-inherited-blindness-developed-by-university-of-pennsylvania-and-chop)