4D-150

Dive Brief:People with a common form of macular degeneration needed far fewer injections to manage their eye condition following treatment with an experimental gene therapy developed by 4D Molecular Therapeutics, the company said Wednesday.Study investigators found 4D Moleculars therapy reduced patients treatment burden by between 83% and 98%, depending on the severity of their disease and when they were diagnosed. The therapy, which is delivered via an eye injection, appeared to have a safety profile roughly in-line with available medicines, like Eylea and Vabysmo.4D Molecular also shared its plans for a Phase 3 study program of its gene therapy, which will involve two randomized trials comparing the experimental treatment to Eylea. However, investors didnt receive news of the data well, sending shares in the biotechnology company down by as much as 25% Thursday.Dive Insight:4D Molecular is one of a handful of developers testing genetic treatments for conditions of the eye. Seven years ago, the field produced the first gene therapy approved in the U.S. for an inherited disease, Spark Therapeutics Luxturna.But progress has been rockier since then, despite periodic investments by large pharmaceutical companies in biotechs like Spark that have driven research forward. A big acquisition by Biogen never panned out, as did another by Novartis. Several biotechs that have remained independent have hit either research or business roadblocks.4D Moleculars research is led by a treatment dubbed 4D-150, which its developing for wet age-related macular degeneration and diabetic macular edema. The results it unveiled Wednesday are in the former condition and come from several cohorts of patients enrolled in a Phase 1/2 trial.In wet AMD, 4D Moleculars goal is to lessen the frequent eye injections used to slow vision loss from the common condition, in which abnormal blood vessels grow into the center of the retina and cause visual distortion. Without treatment, the condition can eventually progress to blindness.4D focused its analysis of the results on the percentage of patients who remained injection free after its treatment, or needed only one supplemental injection. Among the 24 people with severe disease enrolled into the Phase 1/2a portion of the trial, 44% were injection free through one year. Overall, investigators reported an annualized reduction in injections of 83%. Those figures were 70% and 89%, respectively, in a broader group of 30 patients, and 98% and 87% among 15 newly diagnosed patients.Only 2 of the 71 patients overall who received the companys target dose of 4D-150 experienced intraocular inflammation, on the high end but within range of rates observed in testing of Eylea, Vabysmo and a new, longer-lasting formulation of Eylea.Analysts who follow 4D Molecular viewed the results as positive, but acknowledged a debate over how efficacious the companys treatment might ultimately be.Bears will point to eroding injection-free rates, especially in severe patients, while bulls will point to stabilization of efficacy in the post-24 week period, Mani Foroohar, an analyst at Leerink Partners, wrote in a client note, using the metonyms by which Wall Street refers to skeptics and optimists.Kelly Shi, an analyst at Jefferies, wrote that 4D-150s benefits seem correlated with disease severity, which she said should bode well for Phase 3 trials the company has planned. We think the highest bar is on safety, for which 4D continues to differentiate.4D Molecular said it plans to test 4D-150 in two Phase 3 studies that compare it to a once-every-two-month dose of 2 milligram Eylea. It expects to begin enrolling the first in the first quarter of next year.Regenxbio is also developing a gene therapy for AMD with partner AbbVie. Phase 3 studies are already underway. Adverum Biotechnologies is advancing a prospect towards late-stage testing as well. '

iStock, Love Employee 4D Molecular Therapeutics reported its experimental gene therapy demonstrated a nearly 90% reduction in the need for annualized standard-of-care injections in patients with wet age-related macular degeneration. 4D Molecular Therapeutics announced on Wednesday that its investigational gene therapy 4D-150 demonstrated durable clinical activity in the Phase I/II PRISM study of patients with wet age-related macular degeneration. In a 30-patient cohort, 4D-150 cut the need for standard-of-care injections by 89% through 52 weeks of follow-up, and 70% of these patients were injection-free, according to 4DMT’s announcement. In another cohort of 27 patients with severe disease, the need for standard-of-care treatment dropped by 83% and 44% were injection-free. The gene therapy also resulted in sustained benefits in terms of central subfield thickness and mean best-corrected visual acuity. In terms of safety, PRISM found 4D-150 to be well-tolerated. The frequency for of intraocular inflammation (IOI) was consistent with approved anti-VEGF therapies, which are currently widely used to treat age-related macular degeneration (AMD). Overall, 4DMT documented two IOI episodes in all 71 wet AMD patients enrolled, yielding an incidence rate of 2.8%. There were no cases of retinal artery occlusions, hypotony, vasculitis, choroidal effusions and endophthalmitis related to the gene therapy. 4DMT CEO David Kirn in a statement called 4D-150 a “potentially paradigm shifting product candidate,” noting that PRISM’s findings highlight “clear reduction in overall treatment burden and potential multiyear clinical benefit in previously treated patients.” The California-based biotech will continue to invest in 4D-150’s development, Kirn said, and push it into late-stage studies. Alongside the PRISM readout on Wednesday, 4DMT detailed the design of its Phase III 4FRONT development program for 4D-150, which is set to include two double-masked, randomized non-inferiority trials, compared with on-label treatment with Bayer and Regeneron’s Eylea (aflibercept). The gene therapy will be given at a single 3E10 vg/eye dose. The first study under this program, dubbed 4FRONT-1, has a target enrollment of 500 patients and is set to start in the first quarter of 2025, Kirn said. The Phase III program design is in alignment with feedback from the FDA under its Regenerative Medicine Advanced Therapy Designation, according to 4DMT. 4D-150 is an investigational gene therapy that uses an intravitreal vector to deliver a transgene that encodes for aflibercept—the active ingredient of Eylea—and an RNAi molecule that blocks the VEGF-C protein. This mechanism of action allows 4D-150 to suppress four different VEGF proteins in the eye, disrupting the key disease pathway in wet AMD. With 4D-150, 4DMT is seeking to offer a one-time alternative to Eylea, which is injected into the eye every eight weeks , following an initiation regimen. Eylea has become a top-selling treatment in the ophthalmology space. In 2023, the product brought in $5.9 billion in sales worldwide.