Using custom AAV capsids to improve drug delivery ophthalmic gene therapy Phase 1 trial results are positive

On October 10, 2021, 4D Molecular Therapeutics (4DMT) announced that its intravitreal injection of gene therapy 4D-125 has achieved a positive mid-term in a phase 1/2 clinical trial for patients with advanced X-linked retinitis pigmentosa (XLRP) Safety and clinical activity data

X-linked retinitis pigmentosa is a slowly progressing hereditary retinal dystrophy, caused by mutations in the RPGR gene, which can lead to vision loss and even blindness

4D-125 uses the R100 AAV vector developed by this platform, which can target retinal photoreceptor cells to specifically deliver the PRGR gene

▲4D-125 mechanism of action (picture source: reference [2])

As of September 1, 2021, the ongoing dose-escalation and dose-amplification phase 1/2 clinical trial has enrolled 8 patients with advanced X-linked retinitis pigmentosa due to mutations in the RPGR gene

The key data obtained in the mid-term are as follows:

4D-125 was well tolerated in all 8 patients, including 5 patients who received the highest dose of 1E12 vg/eye

No dose-limiting toxicity or serious adverse events were observed

The data of 2 patients with evaluable efficacy showed that the photoreceptor cells of the treated eyes were better preserved compared with the untreated control eyes of the same patient at a follow-up of at least 6 months

Based on the interim data, the researchers plan to continue to recruit patients in the dose expansion cohort at the highest dose level of 1E12 vg/eye, including patients with earlier disease

Reference materials:

[1] 4D Molecular Therapeutics Presents Interim Results from the Ongoing 4D-125 Phase 1/2 Clinical Trial in Patients with Advanced X-linked Retinitis Pigmentosa at the ASRS Annual Meeting.

[2] 4D Molecular Therapeutics.