According to the company, initial interim Phase 2 efficacy data is expected to be presented in H1 2024. It also is expected to provide an update regarding Phase 3 pivotal trial plans in Q1 2024 after discussion with the FDA later this year.
4D Molecular Therapeutics this week announced that it has completed enrollment of the Phase 2 Dose Expansion stage of the PRISM clinical trial for patients with wet age-related macular degeneration (wet AMD) over approximately two quarters and that no significant 4D-150 safety events or inflammation have been reported to date.
In a news release, Robert Kim, MD, chief medical officer of 4DMT, pointed out the speed of enrollment demonstrates the need for therapies for wet AMD.
“The rapid enrollment of the Phase 2 Dose Expansion stage of the PRISM trial is indicative of the high demand by wet AMD patients and physicians for a new safe and effective therapy delivered by routine outpatient intravitreal injection with the potential to significantly reduce the need for frequent anti-VEGF injections,” Kim said in the news release. “We thank the PRISM investigators and patients for their enthusiasm for this important study as we rapidly advance 4D-150 towards the next stage of development.”
The company noted in its news release 4D-150 is comprised of its customized and evolved intravitreal vector, R100, and a transgene payload that expresses both aflibercept and a VEGF-C inhibitory RNAi. This dual transgene payload inhibits 4 angiogenic factors that drive wet AMD and DME: VEGF A, B, C and PlGF. R100 was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform. 4D-150 is designed for single, low-dose intravitreal delivery.
According to 4DMT, the Dose Expansion stage of the PRISM trial is a multicenter, randomized study designed to evaluate the safety and efficacy of 4D-150 at two different dose levels in wet AMD patients with high anti-VEGF need (annualized mean anti-VEGF injection frequency in preceding 12 months was approximately 10). The targeted enrollment of the trial was 50 wet AMD patients randomized 2:2:1 to 3E10 vg/eye or 1E10 vg/eye of 4D-150 or aflibercept. The Best-Corrected Visual Acuity (BCVA) inclusion criteria at baseline for this stage was 34-83 Early Treatment Diabetic Retinopathy Study (ETDRS) letters compared to 25-78 for the Phase 1 Dose Exploration stage.
The company noted that as of July 3, 2023, for patients enrolled in Dose Expansion with maximum follow-up through 20 weeks, no treatment-emergent Grade ≥1 inflammatory cells or required deviations from the 20-week protocol-specified corticosteroid eyedrop taper were reported. In addition, no hypotony, no vasculitis and no treatment-related serious adverse events were reported.
Moreover, the company pointed out initial interim Phase 2 clinical activity data, and further safety data updates, are expected to be reported in H1 2024. Company officials noted in the news release they expect to have initial discussions with the FDA on Phase 3 pivotal trial design for 4D-150 for patients with wet AMD in Q4 2023, and we expect to provide an update on pivotal trial plans in Q1 2024.
David Kirn, MD, co-founder and CEO of 4DMT, said company officials are pleased by the rapid pace and completion of enrollment of the Phase 2 PRISM trial driven by strong patient and physician interest.
“We believe it speaks to 4D-150’s clinical differentiation, including its potential as a safe, single-dose, routine, intravitreal injection-based durable therapeutic, its multitargeted mechanism-of-action with inhibition of four VEGF family members, and our strong Phase 1 clinical activity signals reported to date,” he said in the news release. “We believe that 4D-150’s differentiated profile has the potential to also drive rapid enrollment in our DME program, and we expect to enroll our first patient in the Phase 2 SPECTRA trial in Q3 2023. We remain committed to the advancement of our large market ophthalmology product candidates, including 4D-150 for wet AMD and DME as well as 4D-175 for geographic atrophy.”
The company pointed out in its news release data from the Phase 2 PRISM clinical trial are preliminary and will need additional confirmation from longer follow-up. Preliminary data from 4DMT’s clinical trials that it announces or publishes may change as more patient data becomes available and are subject to audit and verification procedures that could result in material changes in the final data.