Skip to main content

AAV5-RPGR Gene Therapy for RPGR-Associated X-Linked Retinitis Pigmentosa- Janssen (Johnson & Johnson) & MEIRAGTx

Highlights of AAV5-RPGR Gene Therapy Program

- AAV5-RPGR is an investigational gene therapy product for RPGR-Associated X-Linked Retinitis Pigmentosa
- Developed by Janssen (Johnson & Johnson) & MEIRAGTx
- 12-months ongoing Phase 1 & 2 clinical trial data  were presented at AAO 2020 conference
- Data showed that low and intermediate doses were well-tolerated
-  Demonstrated statistically significant sustained or increased vision improvement across multiple metrics and modalities

RPGR-Associated X-Linked Retinitis Pigmentosa

In patients with XLRP, the photoreceptors that are responsible for converting light into signals that are sent to the brain, function poorly, leading to a degeneration of the retina and legal blindness in adulthood. 

Gene Therapy Platform
AAV5-RPGR is an investigational gene therapy product. It is delivered via subretinal injection targeting the central retina in the eye that was more affected at baseline.

Regulatory Status of AAV5-RPGR Gene Therapy Program

U.S. Food and Drug Administration (FDA)
Received Fast Track designation from the FDA, Orphan designations from the FDA.

The European Medicines Agency (EMA)
EMA granted PRIME (PRIority MEdicines) and Advanced Therapy Medicinal Product (ATMP) designations to AAV-RPGR. Orphan designations from the EMA.

Clinical Trial Update of AAV5-RPGR Gene Therapy Program

GT009 (NCT03252847) is an open-label, multi-center, dose-escalation trial, which enrolled patients aged five years and older with XLRP caused by mutations in RPGR at multiple sites in the United States and the United Kingdom. 

The primary endpoint was safety and tolerability; secondary endpoints assessed retinal sensitivity, visual function, functional vision, and quality of life measurements. The ongoing Phase 1/2 clinical trial consists of three phases: dose-escalation, dose-confirmation, and dose-expansion. In the dose-escalation phase (n=10), adults were administered low, intermediate, or high dose AAV-RPGR. AAV-RPGR is delivered via subretinal injection targeting the central retina in the eye that was more affected at baseline. The patient's other eye served as an untreated control.

Safety

Safety data to date has demonstrated ocular and systemic safety profiles that are anticipated and manageable. The most common adverse events were related to the surgical procedure, transient, and resolved without intervention. In the high dose cohort (n=3), inflammation was evident in two of three adults, and measures of visual function were not improved.

Efficacy
Statistically significant differences in mean retinal sensitivity were observed between treated and untreated eyes in the intermediate dose cohort: 1.05 decibel (dB); (90% CI: 0.81, 1.29).
Statistically significant differences were observed in central visual field progression rate (V30) between treated and untreated eyes in the low: 1.10 dB-sr (steradian)/year; (90% CI: 0.10, 2.10) and intermediate: 1.26 dB-sr/year; (90% CI: 0.65, 1.86) dose cohorts.

Efficacy signals were observed at first post-treatment assessments at three months with improvements sustained or increased at 12 months.



Reference
https://www.janssen.com/
https://meiragtx.com/
https://www.prnewswire.com/news-releases/late-breaking-12-month-data-of-investigational-rpgr-gene-therapy-shows-statistically-significant-and-continued-vision-improvement-in-patients-with-x-linked-retinitis-pigmentosa-301173016.html
https://meiragtx.com/wp-content/uploads/2020/11/AAO_2020_RPGR_12_month.pdf

Comments

Popular posts from this blog

Carbohydrate Metabolism: MCQs and answers on Glycolysis & Gluconeogenesis

                                      MCQ on Glycolysis & Gluconeogenesis 1) Which of the following enzyme is not involved in galactose metabolism? a) Glucokinase b) Galactokinase c) Galactose-1-Phosphate Uridyl transferase d) UDP-Galactose 4- epimerase 2) Which of the following enzyme is defective in galactosemia (type I) - a fatal genetic disorder in infants? a) Glucokinase b) Galactokinase c) Galactose-1-Phosphate Uridyl transferase d) UDP-Galactose 4- epimerase 3) In the liver, the accumulation of which of the following metabolite attenuates the inhibitory of ATP on phosphofructokinase? a) Glucose-6-Phosphate b) Citrate c) Fructose-1,6-Bisphosphate d) Fructose-2,6-Bisphosphate 4) Mutation in which of the following enzymes leads to a glycogen storage disease known as "Tarui’s disease"? a) Glucokinase b) Phosphofructokinase c) Phosphoglucomutase d) Pyruvate Kinase 5) E...

MCQs and Answers on cultivation (culture/incubation), Isolation and Identification of microorganisms: Medical Microbiology

40 plus questions - Multiple Choice Questions on Classification, Culture, and Identification of the microorganisms 1. Which of the following microorganism has the cocci cell shapes and sizes arranged usually in tetrad structures? a)  Streptococcus pneumoniae b)  Staphylococcus aureus c)  Chlamydia trachomatis d)  Neisseria meningitidis 2. What are the different growth morphology and cell structures used for the classification of fungi? Select all the correct answers: a) Yeast b) Mold c) Mycelia d) Protozoa 3. Which of the following media is formulated with additional nutrients to support the growth of fastidious or nutritionally demanding bacteria that may not grow well on basic media? a) Differential media b) Enriched media c) Nutrient agar (media) d) Selective media 4. Which of the following metabolic characteristic is a distinguishing characteristic and identification of colonies of  E. coli ? a) Hydrogen sulfide formation b) Indole Formation c) Lactose fe...

Multiple Choice Questions (MCQs) on Diabetes Mellitus: Pathogenesis, Diagnosis and Treatment

                                        MCQs on Diabetes mellitus 1) Diabetes mellitus is a disorder characterized by hyperglycemia.  Which of the following is not the common characteristic features of type 2 diabetes mellitus ? a) Impaired insulin secretion b) Increased Insulin resistance  c) Diabetic ketoacidosis d) Excessive hepatic glucose production 2) Which of the following are the characteristic features of type 1 diabetes mellitus? a) Type 1 diabetes is caused by an absolute deficiency of insulin. b) Type 1 diabetes is associated with the autoimmune destruction of beta cells.  c) Patients with  uncontrolled type 1 diabetes present with diabetic ketoacidosis d) All of the above   3) Which of the following serum measurements are not used for the diagnosis of diabetes mellitus? a) Fasting blood glucose d) Postprandial blood glucose  c) Insulin ...