dm+d

Unassigned

New Medicines

X-linked retinitis pigmentosa (XLRP)

Information

New molecular entity
Applied Genetic Technologies Corporation
Applied Genetic Technologies Corporation

Development and Regulatory status

None
None
Phase II Clinical Trials
Yes
Yes
Nov 20Has orphan drug status in EU and US [5].

Category

A recombinant adeno-associated virus vector (AAV) expressing the human RPGR-ORF15 gene.
The prevalence of RP is estimated at ~1 in 5,000 individuals. XLRP accounts for 6-10% of cases [1,2]. This means ~ 1000 people in England are likely to affected at on time but not all will be eligible for this.
X-linked retinitis pigmentosa (XLRP)
Subretinal injection
Parenteral

Trial or other data

Nov 20The PII/III Vista trial will include a low-dose group (the 1.2E+11 vg/mL, Group 2 dose from the ongoing PI/II trial), a high-dose group (the 1.1E+12 vg/mL, Group 5 dose from the ongoing PI/II trial), and an untreated control group. The primary endpoint will be based on visual sensitivity defined having at least a 7 decibel improvement in visual sensitivity in at least 5 pre-specified loci at month 12. This primary endpoint was informed by recent comments that the Company received from the FDA on what evidence would help support a showing of a clinically meaningful improvement on microperimetry at the Group 2 and Group 5 doses. The Company plans to use this endpoint as one of several measures of visual sensitivity that have the potential to support a clinically meaningful benefit [4].
Nov 20AGTC plans to initiate enrolment in a planned PI/II expansion trial (Skyline) in 4Q 2020 and a Phase II/III trial (Vista) in 1Q 2021. The Skyline trial will enrol 12 additional patients total in Group 2 (1.2E+11 vg/mL) and Group 5 (1.1E+12 vg/mL). The Vista trial will enrol 60 patients in the US. AGTC plans to submit a six-month interim analysis of the data from this study to the US FDA to obtain feedback on its development plan to support drug approval. The company plans to discuss the possible final dose selection for the treatment of the contralateral eye based on this six-month interim data, with the US FDA [4].
Nov 20AGTC announces positive data from its ongoing PI/II trial. Visual sensitivity, visual acuity and safety data were reported for 12-month timepoints for Groups 2 and 4, and 6-month time points for Groups 5 and 6. Eight of the 11 patients in Groups 5 and 6 would meet the eligibility criteria for AGTC’s future XLRP trials, and five of these eight (62%), met the definition for response based on an improvement of at least 7 decibels in at least 5 loci [4].
Apr 18PI/II dose escalation study to assess the safety and efficacy of AGTC 501 in patients with X-linked retinitis pigmentosa starts (AGTC-RPGR001; NCT03316560). Low, middle and high dose of an adeno associated virus (AAV) vector expressing human RPGR gene will be received by individuals in groups 1, 2 and 3, while the maximum tolerated dose as determined by the first three groups will be received by participants in group 4, enrolled sequentially in four groups. 30 patients aged 6 years and older will be recruited in the US (no UK sites). Collection of primary safety outcome data is expected to complete Mar 23 and other efficacy data Mar 25 [3].