Topline results from a mid-stage study show that 4D Molecular Therapeutics’ investigational gene therapy cut annual rates of Eylea injections by 85% and 89% for the low and high doses, respectively.
Pictured: Healthcare worker conducting an eye exam on a female patient/iStock, peakSTOCK
4D Molecular Therapeutics on Saturday unveiled topline results from its Phase II PRISM study, showing that its investigational gene therapy 4D-150 can significantly ease treatment burden in patients with wet age-related macular degeneration.
Over 24 weeks of follow-up, 84% of patients treated with 4D-150’s higher 3E10-vg/eye dose did not need supplemental injections with Regeneron and Bayer’s Eylea (aflibercept), a cornerstone anti-VEGF therapy for wet age-related macular degeneration (AMD). At the lower dose group of 1E10 vg/eye, only one patient needed supplemental Eylea.
Also, 63% and 50% of patients in the high- and low-dose groups, respectively, did not need supporting Eylea treatment. Overall, the high dose level of 4D-150 reduced annual Eylea injections by 89%, while the lower dose cut Eylea rates by 85%.
In terms of safety, PRISM found no instance of significant inflammation, even in the high-dose group. In addition, 97% of treated patients completed their 20-week prophylactic topical corticosteroid taper according to schedule, while none of the patients were on steroids at the time of data collection.
4DMT reported these data at the Angiogenesis, Exudation, and Degeneration 2024 Conference, held virtually on Friday.
CEO David Kirn said in a statement that the company is “thrilled” about these data, which “strongly validate 4D-150’s potential as a safe, convenient, durable and transformational intravitreal therapeutic for wet AMD patients, with a goal of preserving vision for the longer term.”
“We believe 4D-150 has the potential to disrupt the current treatment paradigm in these patients,” Kirn added.
4D-150 is an investigational gene therapy that delivers a transgene cassette that expresses both aflibercept and an RNA interference molecule that blocks the VEGF-C protein. The double-payload approach allows 4D-150 to inhibit four VEGF family members—VEGF A, B, C and PIGF—which are central to the pathology of wet AMD and diabetic macular edema.
The investigational gene therapy also uses 4DMT’s proprietary R100 vector, which enables its single, low-dose intravitreal delivery that avoids significant inflammation.
4DMT is planning to take 4D-150 into late-stage studies based on ongoing talks with the FDA and European Medicines Agency. The first Phase III study, which is set to launch in the first quarter of 2025, will be a non-inferiority study versus Eylea using the higher dose of 4D-150.
In the latter half of 2024, the company is expecting interim 24-week landmark data analysis from PRISM’s population extension cohort, which is looking at 4D-150 in a patient population with broader disease severity.
4DMT is also trialing the gene therapy in diabetic macular edema, for which it is running the Phase II SPECTRA study. Initial data and analysis are also expected in the latter half of 2024.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
