BACKGROUND

Botaretigene sparoparvovec is an investigational adeno-associated virus vector type 5 (AAV5) gene therapy being studied for the treatment of X-linked retinitis pigmentosa (XLRP) associated with disease causing sequence variants in the retinitis pigmentosa GTPase regulator (RPGR) gene.^1-4 Botaretigene sparoparvovec is designed to deliver a stable gene sequence to rod and cone photoreceptors to drive expression of functional RPGR protein in the area of rescuable retina which is currently being investigated in its role to preserve vision.^1,2,5

CLINICAL DATA

Study Design

The LUMEOS study⁶(MGT-RPGR-021) is a phase 3, randomized, controlled, multicenter, clinical trial conducted to evaluate the efficacy and safety of bilateral subretinal administration of botaretigene sparoparvovec in participants with XLRP due to variants in the RPGR gene. Please visit https://clinicaltrials.gov (identifier NCT04671433) for more information.⁷

The LUMEOS study⁶ includes a phase 3, randomized, controlled, multicenter, follow-up clinical trial (MGT-RPGR-022). Please visit https://clinicaltrials.gov (identifier NCT04794101) for more information.⁸

There are 3 treatment arms in the clinical trial with an enrollment of 97 participants: immediate treatment groups (n=64) are given either low dose or intermediate or deferred treatment group (n=33) receives no intervention and will be administered intermediate dose in the follow-up study (MGT-RPGR-022). Treatment is bilateral subretinal and all participants will be followed for 60 months.^7,8

Inclusion and Exclusion Criteria

Inclusion criteria include male or female sex, 3 years of age or older, and have XLRP confirmed by a retinal specialist and has a predicted disease causing sequence variant in RPGR confirmed by an accredited laboratory.⁷

Exclusion criteria includes:⁷

• Had ocular surgery within 3 months prior to screening or is anticipated to require ocular surgery within 6 months after student intervention administration
• Any investigational ocular treatment or any other ocular treatment that could confound the interpretation of the efficacy results or affect participant compliance with the visit schedule
• Has undergone prior retinal surgery involving the macula, macular laser photocoagulation, external-beam radiation therapy, transpupillary thermotherapy, glaucoma filtration surgery or corneal surgery

Primary and Secondary Outcomes

The primary outcome is change from baseline to week 52 in vision-guided mobility assessment (VMA) as measured by the ability to navigate through a VMA maze.⁷

The secondary outcomes, measured from baseline to week 52, are as follows:⁷

• Change in mean retinal sensitivity within the central 10 degrees excluding scotoma in static perimetry
• Change in mean retinal sensitivity of worse-seeing eye within the central 10 degrees excluding scotoma in static perimetry
• Change in retinal function as assessed by:
  • Pointwise response in full visual field
  • Pointwise response in worse-seeing eye in full visual field
  • Pointwise response in the central 30 degrees visual field
  • Pointwise response in worse-seeing eye in the central 30 degrees visual field
  • Mean retinal sensitivity within the full visual field in static perimetry
• Change in functional vision by using VMA assessment in the worse-seeing eye
• Change in the Modified Low Luminance Questionnaire Extreme Lighting Domain score
• Change in visual function as assessed by:
  • Monocular low luminance visual acuity using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score
  • Monocular best corrected visual acuity using the ETDRS chart letter score
  • Low luminance visual acuity using the ETDRS chart letter score in worse-seeing eye
• Safety and tolerability as assessed day 1 to week 52 by:
  • Number of participants with ocular and non-ocular adverse events
  • Number of participants with abnormalities in laboratory assessments

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 21 May 2024.