dm+d

Unassigned

New Medicines

Information

New molecular entity
REGENXBIO
REGENXBIO

Development and Regulatory status

None
None
Phase III Clinical Trials
Jan 22BLA expected to be submitted to FDA in 2024 based on tow pivotal trials, ASCENT and the ongoing ATMOSPHERE trial [9]
Sep 21AbbVie and REGENXBIO enters into a partnership to develop and commercialise RGX 314. AbbVie will lead the clinical development and commercialisation of RGX 314 globally and will lead manufacturing of RGX 314 for commercial supply outside the US. [2-4]
Jan 21REGENXBIO announces intention to submit Biologics license application (BLA) to the US FDA for wet AMD in 2024. [8]

Category

AAV8 vector carries gene encoding for monoclonal antibody fragment, ranibizumab, which binds to & neutralises activity of vascular endothelial growth factor (VEGF), modifying the pathway new leaky blood vessel formation and retinal fluid accumulation.
The estimated prevalence of AMD in the UK is 4.8% of those over 65 years of age and 12.2% of those aged 80 years or more. There are around 70,000 new diagnoses in the UK each year [1].
Choroidal neovascularization (CNV) secondary to wet age-related macular degeneration (AMD) in people aged ≥50 years
Subretinal injection
Parenteral

Trial or other data

Jan 22REGENXIBO initiates PIII ASCENT trial to evaluate RGX-314 in patients with wet AMD. ASCENT is a multi-center, randomized, active-controlled trial evaluating the efficacy and safety of RGX-314 across two dose arms, 6.4x1010 genomic copies per eye (GC/eye) and 1.3x1011 GC/eye, versus intravitreal injections of aflibercept. The primary endpoint of the trial is non-inferiority to aflibercept based on the change from baseline in Best Corrected Visual Acuity (BCVA) at one year. The trial will enroll approximately 465 patients across the two dose arms and the aflibercept control arm [9].
Oct 21The pivotal PII/III RCT, ATMOSPHERE, (n=300, NCT04704921) is recruiting pts to assess the mean change in BCVA to 54 weeks in pts with wet AMD randomised to single dose of RGX 314 or monthly Lucentis. The estimated primary completion date is March 2023 with full data expected March 2024. Another pivotal trial is also planned in Q4 2021.[2-4,7]
Oct 21Interim data from PI/II AAVIATE trial (NCT04514653) showed that 14 pts dosed with RGX 314 in cohort 1 demonstrated stable visual acuity (VA) at 6 months with a mean Best Corrected Visual Acuity (BCVA) change of -2.8 letters (95% CI: -7.0 to 1.4) from day 1 and -0.6 letters (-5.2 to 4.0) from week 1. Stable central retinal thickness (CRT)at 6 months was reported. Five pts receiving monthly injections of ranibizumab demonstrated mean BCVA change at 6 months of +6.8 letters (-3.3 to 16.9) from day 1 and +3.0 letters (-4.7 to 10.7) from week 1. Pts on monthly injections of ranibizumab also demonstrated stable CRT at 6 months from day 1. A significant reduction in anti-vascular endothelial growth factor (anti-VEGF) treatment burden was reported with RGX 314 vs. monthly injections. The trial is due to complete in Feb 22. [2-4,6]
Feb 21REGENXBIO initiated an open label, PII interventional trial (n=60, NCT04832724) for the estimation of pharmacodynamics of two doses in two formulations of RGX 314 gene therapy administered via subretinal delivery in pts with wet AMD. Results are expected mid 2022. [2-5]

Diabetic retinopathy without center-involved diabetic macular oedema

Information

New molecular entity
REGENXBIO
REGENXBIO

Development and Regulatory status

None
None
Phase II Clinical Trials

Category

AAV8 vector carries gene encoding for monoclonal antibody fragment, ranibizumab, which binds to & neutralises activity of vascular endothelial growth factor (VEGF), modifying the pathway new leaky blood vessel formation and retinal fluid accumulation.
Diabetic retinopathy is the most common form of diabetic eye disease. 1,280 new cases of blindness caused by diabetic retinopathy are reported each year in England alone, while a further 4,200 people in the country are thought to be at risk of retinopathy-related vision loss. [1]
Diabetic retinopathy without center-involved diabetic macular oedema
Subretinal injection
Parenteral

Trial or other data

Feb 22Company announces positive interim analysis data for PII ALTITUDE trial (NCT04567550). Cohort 1 (n= 20) were randomised to receive RGX-314 at a dose level of 2.5x10^11 gc/eye vs observational control at a 3:1 ratio. At 6 months, of 15 pts were dosed with RGX-314 in cohort 1, 47% demonstrated a ≥2 step improvement from baseline on the ETDRS-DRSS at six months, compared to 0% of pts in observational control; increase from 33% of pts at three months. RGX-314 was well tolerated in 15 pts from cohort 1 with no drug-related serious adverse events at six months. No intraocular inflammation observed. Enrollment is continuing for the remainder cohorts [4]
Nov 20PII randomised, dose-escalation, observation-controlled trial (ALTITUDE) of RGX 314 for the treatment of pts with diabetic retinopathy was initiated in the US (NCT04567550, n=60). Pts were aged 25-89 with moderately severe or severe nonproliferative diabetic retinopathy or mild proliferative diabetic retinopathy. Primary outcome measures include evaluating the effect of RGX-314 on diabetic retinopathy by the Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (-DRSS) at week 48. Safety and tolerability were secondary outcome measures. Doses to be administered are reported to be 2.5x10^11 gc/eye and 5.0x10^11 gc/eye. Estimated primary study completion is Feb 2022 [2, 3]