4DMT Presents Positive 52-Week Results from Phase 2b Cohort of PRISM Wet AMD Study and Long-term Durability Data Supporting 4D-150 4FRONT Global Registration Program
4D Molecular Therapeutics (FDMT) announced positive 52-week results from its Phase 2b PRISM trial evaluating 4D-150 in wet age-related macular degeneration (wet AMD). The 3E10 vg/eye dose achieved an 83% reduction in injection burden compared to standard aflibercept treatment, with 70% of patients requiring 0-1 supplemental injection and 57% remaining injection-free through 52 weeks.
In the recently diagnosed subgroup, results were even more promising, with 87% requiring 0-1 supplemental injection and 80% remaining injection-free. The treatment demonstrated durable and stable aflibercept expression across all cohorts with up to two years of follow-up. Safety data showed good tolerability with up to three years of follow-up.
The company plans to initiate Phase 3 trials 4FRONT-1 and 4FRONT-2 in Q1 and Q3 2025, respectively, with primary endpoint topline data expected in H2 2027.
4D Molecular Therapeutics (FDMT) ha annunciato risultati positivi a 52 settimane dal suo studio clinico di Fase 2b PRISM che valuta il 4D-150 nella degenerazione maculare senile umida (wet AMD). La dose di 3E10 vg/occhio ha raggiunto una riduzione dell'83% del carico di iniezione rispetto al trattamento standard con aflibercept, con il 70% dei pazienti che ha richiesto 0-1 iniezione supplementare e il 57% che è rimasto senza iniezioni per 52 settimane.
Nel sottogruppo recentemente diagnosticato, i risultati sono stati ancora più promettenti, con l'87% che richiede 0-1 iniezione supplementare e l'80% che è rimasto senza iniezioni. Il trattamento ha dimostrato un'espressione duratura e stabile di aflibercept in tutte le coorti con un follow-up di fino a due anni. I dati sulla sicurezza hanno mostrato una buona tollerabilità con un follow-up di fino a tre anni.
La società prevede di avviare gli studi di Fase 3 4FRONT-1 e 4FRONT-2 nel primo e nel terzo trimestre del 2025, rispettivamente, con i dati principali attesi nella seconda metà del 2027.
4D Molecular Therapeutics (FDMT) anunció resultados positivos a 52 semanas de su ensayo de Fase 2b PRISM que evalúa el 4D-150 en la degeneración macular relacionada con la edad húmeda (wet AMD). La dosis de 3E10 vg/ojo logró una reducción del 83% en la carga de inyecciones en comparación con el tratamiento estándar de aflibercept, con el 70% de los pacientes requiriendo 0-1 inyección suplementaria y el 57% permaneciendo sin inyecciones durante 52 semanas.
En el subgrupo de diagnóstico reciente, los resultados fueron incluso más prometedores, con el 87% requiriendo 0-1 inyección suplementaria y el 80% permaneciendo sin inyecciones. El tratamiento demostró una expresión duradera y estable de aflibercept en todos los grupos con un seguimiento de hasta dos años. Los datos de seguridad mostraron una buena tolerancia con un seguimiento de hasta tres años.
La empresa planea iniciar ensayos de Fase 3 4FRONT-1 y 4FRONT-2 en el primer y tercer trimestre de 2025, respectivamente, con los datos principales esperados en la segunda mitad de 2027.
4D 분자 치료학 (FDMT)은 습성 노인성 황반변성(wet AMD)에 대한 4D-150을 평가하는 2b상 PRISM 시험에서 52주 긍정적인 결과를 발표했습니다. 3E10 vg/눈 용량은 표준 아플리버셉트 치료에 비해 주사 부담을 83% 감소시켰습니다, 환자의 70%가 0-1회의 보조 주사를 필요로 했으며 57%는 52주 동안 주사 없이 지냈습니다.
최근 진단된 하위 그룹에서는 결과가 더욱 유망하여 87%가 0-1회의 보조 주사가 필요했습니다 그리고 80%는 주사 없이 지냈습니다. 치료는 모든 집단에서 최대 2년의 경과 관찰 동안 지속적이고 안정적인 아플리버셉트 발현을 보여주었습니다. 안전성 데이터는 최대 3년의 경과 관찰에서 좋은 내약성을 나타냈습니다.
회사는 각각 2025년 1분기와 3분기에 3상 시험 4FRONT-1 및 4FRONT-2를 시작할 계획이며, 주요 목표 데이터는 2027년 하반기에 예상됩니다.
4D Molecular Therapeutics (FDMT) a annoncé des résultats positifs à 52 semaines de son essai de Phase 2b PRISM, évaluant le 4D-150 dans la dégénérescence maculaire liée à l'âge humide (wet AMD). La dose de 3E10 vg/œil a permis une réduction de 83% de la charge d'injection par rapport au traitement standard par aflibercept, 70% des patients nécessitant 0-1 injection supplémentaire et 57% restant sans injection pendant 52 semaines.
Dans le sous-groupe récemment diagnostiqué, les résultats étaient encore plus prometteurs, avec 87% nécessitant 0-1 injection supplémentaire et 80% restant sans injection. Le traitement a montré une expression durable et stable d'aflibercept dans toutes les cohortes avec un suivi allant jusqu'à deux ans. Les données de sécurité ont montré une bonne tolérance avec un suivi allant jusqu'à trois ans.
La société projette de lancer les essais de Phase 3 4FRONT-1 et 4FRONT-2 au premier et au troisième trimestre de 2025, respectivement, avec des données clés attendues au second semestre de 2027.
4D Molecular Therapeutics (FDMT) hat positive 52-Wochen-Ergebnisse aus seiner Phase-2b-PRISM-Studie mit 4D-150 bei feuchter altersbedingter Makuladegeneration (wet AMD) bekannt gegeben. Die Dosis von 3E10 vg/Auge erzielte eine Reduktion der Injektionsbelastung um 83% im Vergleich zur Standardbehandlung mit Aflibercept, wobei 70% der Patienten 0-1 zusätzliche Injektionen benötigten und 57% über 52 Wochen injektionsfrei blieben.
In der Subgruppe mit kürzlich Diagnostizierten waren die Ergebnisse noch vielversprechender, mit 87%, die 0-1 zusätzliche Injektionen benötigten und 80%, die injektionsfrei blieben. Die Behandlung zeigte eine langanhaltende und stabile Expression von Aflibercept in allen Kohorten mit einer Nachbeobachtungszeit von bis zu zwei Jahren. Die Sicherheitsdaten zeigten eine gute Verträglichkeit mit einer Nachbeobachtungszeit von bis zu drei Jahren.
Das Unternehmen plant, die Phase-3-Studien 4FRONT-1 und 4FRONT-2 im 1. und 3. Quartal 2025 zu initiieren, wobei die primären Endpunktdaten für das 2. Halbjahr 2027 erwartet werden.
- 83% reduction in injection burden vs. standard treatment
- 70% of patients required 0-1 supplemental injection
- 87% success rate in recently diagnosed subgroup
- Durable efficacy demonstrated up to two years
- Strong safety profile with 3-year follow-up data
- Visual acuity improvement of +2.2 letters in overall population
- Phase 3 trials won't start until 2025
- Primary endpoint data not expected until H2 2027
- 2.8% of patients experienced treatment-related inflammation
Insights
The latest PRISM trial results for 4D-150 represent a potential paradigm shift in wet AMD treatment. The 83% reduction in injection burden compared to standard aflibercept treatment is groundbreaking, as current therapies require frequent hospital visits that significantly impact patient compliance and quality of life.
The data is particularly compelling in newly diagnosed patients, where 80% remained injection-free through 52 weeks. This suggests 4D-150 could fundamentally transform the treatment approach for new patients, potentially positioning it as a first-line therapy. The sustained aflibercept expression over two years indicates that the treatment effect is not just powerful but remarkably durable.
The safety profile is equally impressive, with only 2.8% of patients experiencing mild, transient inflammation. This favorable safety profile, combined with the strong efficacy data, positions 4D-150 as a potential backbone therapy for vascular retinal diseases. The planned initiation of Phase 3 trials (4FRONT-1 and 4FRONT-2) in 2025 puts the company on track for potential commercialization, with primary endpoint data expected in H2 2027.
These results position 4DMT strongly in the lucrative wet AMD market, where current treatments generate billions in annual sales. The dramatic reduction in injection frequency addresses a critical market need and could drive rapid adoption upon approval. The robust efficacy data, particularly in treatment-naïve patients, suggests 4D-150 could become the preferred first-line therapy.
The durability profile could revolutionize the treatment paradigm and significantly reduce the healthcare resource burden. Current standard-of-care treatments require frequent hospital visits, creating substantial costs for healthcare systems and patients. 4D-150's potential to provide multi-year efficacy with minimal supplemental injections could lead to significant cost savings and improved resource allocation.
The planned global registration program with 4FRONT-1 and 4FRONT-2 trials demonstrates confidence in the commercial potential. With primary endpoint data expected in H2 2027, 4DMT is well-positioned to potentially capture significant market share in the expanding wet AMD market.
- 3E10 vg/eye achieved an
83% reduction in injection burden vs. projected on-label aflibercept 2 mg Q8W,70% required 0-1 supplemental injection, and57% were injection-free through 52 weeks - In the recently diagnosed subgroup, which most resembles the Phase 3 4FRONT-1 and 4FRONT-2 patient populations,
87% required 0-1 supplemental injection and80% were injection-free through 52 weeks - Durable and stable aflibercept expression demonstrated across all 3E10 vg/eye PRISM cohorts, with up to two years of follow-up
- 4D-150 continues to be well tolerated, with up to three years of follow-up
- 4FRONT-1 and 4FRONT-2 are on target to initiate in Q1 and Q3 2025, respectively
- Company to host webcast on Monday, February 10, 2025 at 8:00 a.m. ET
EMERYVILLE, Calif., Feb. 08, 2025 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (Nasdaq: FDMT; 4DMT or the Company), a leading clinical-stage company focused on unlocking the full potential of genetic medicines to treat large market diseases, today announced positive initial interim 52-week data from the Phase 2b Population Extension cohort of the PRISM clinical trial evaluating 4D-150 in a broad wet age-related macular degeneration (wet AMD) patient population. Additional data were provided on the durability of aflibercept expression for up to two years. The data were presented by Dante Pieramici, M.D., in an oral presentation titled “Phase 2b Population Extension Cohort Evaluating 4D-150 in Neovascular Age-Related Macular Degeneration: 52-Week Results” at Angiogenesis, Exudation, and Degeneration 2025.
“We believe 4D-150 has paradigm-shifting potential. 4D-150 is designed to achieve favorable tolerability and robust and durable multi-year efficacy following routine intravitreal administration that enables seamless integration into retina clinics,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “The data from the PRISM clinical trial, which evaluated wet AMD patients with a broad range of disease severity and duration, and the initial data from SPECTRA in diabetic macular edema (DME), demonstrate 4D-150’s potential to become the first backbone therapy forming the foundation for the treatment of vascular retinal diseases. The ability to deliver disease control with long-lasting freedom from frequent bolus injections addresses the primary unmet need for patients and physicians.”
Topline 52-Week Efficacy Results for 4D-150 3E10 vg/eye (Planned Phase 3 Dose) from Phase 2b Population Extension Cohort of PRISM (Data Cut-Off January 15, 2025):
- Phase 2b (n=30): Broad Wet AMD Disease Activity
- Supplemental aflibercept injections:
83% reduction, representing 0.97 mean supplemental injections per patient over 52-weeks vs. 6.0 injections projected with on-label aflibercept 2 mg Q8W70% 0-1 injection57% injection-free
- Improved and maintained best corrected visual acuity (BCVA) of +2.2 letters
- Durable central subfield thickness (CST) improvement with fewer fluctuations, as measured by optical coherence tomography (OCT), of -11 µm; -13 µm in supplemental injection-free patients
- Supplemental aflibercept injections:
- Phase 2b (n=15): Recently Diagnosed Subgroup
- Supplemental aflibercept injections:
94% reduction, representing 0.33 mean supplemental injections per patient over 52-weeks vs. 6.0 injections projected with on-label aflibercept 2 mg Q8W87% 0-1 injection80% injection-free
- Improved and maintained BCVA of +3.1 letters
- Durable CST improvement with fewer fluctuations, as measured by OCT, of -10 µm; -20 µm in supplemental injection-free patients
- Supplemental aflibercept injections:
4D-150 Safety Update from PRISM (Data Cut-Off January 15, 2025):
- 4D-150 continues to be well tolerated during up to three years of follow up in all patients treated with 3E10 vg/eye
2.8% (2 of 71) had 4D-150–related 1+ intraocular inflammation (IOI) (SUN/NEI scales), which were transient 1+ vitreous cells noted at a single timepoint, as previously reported99% (70 of 71) completed steroid prophylaxis taper on schedule99% (70 of 71) remained completely off steroids
- No 4D-150–related hypotony, endophthalmitis, vasculitis, occlusive/non-occlusive retinal vasculitis, or choroidal effusions observed to date
"The promise of 4D-150 for both patients and clinicians lies in its potential to tackle one of the most pressing unmet needs in vascular retinal diseases—providing a long-lasting, effective treatment option that reduces the frequent burden of bolus anti-VEGF injections,” said Dante Pieramici, M.D., a principal investigator of the PRISM study and member of the 4DMT Ophthalmology Advisory Board. “4D-150 offers a profound shift in how we manage our patients’ care, potentially freeing them from the ongoing challenges of injection frequency while ensuring they maintain the vision improvement characteristic of current standard of care. The data from the PRISM study gives me great hope that 4D-150 can become the backbone of future retinal treatments for wet AMD, offering both clinical benefit and better quality of life for our patients."
PRISM Durability Update from All 3E10 vg/eye Cohorts
- Aqueous humor concentrations were studied serially every three months
- Durable and stable aflibercept expression demonstrated, with up to two years of follow-up, with aqueous humor concentrations consistently within projected therapeutic range
4D-150 Program Milestones
- 4FRONT-1 and 4FRONT-2 expected to initiate in Q1 and Q3 2025, respectively
- Two-year Phase 1/2a and 18-month Phase 2b PRISM data expected in Q4 2025
- Primary endpoint 52-week topline data from both 4FRONT-1 and 4FRONT-2 expected in H2 2027
Corporate Webcast Details
Title: 4D-150 in Broad Wet AMD Population: Interim 52-week Data from Phase 2b & Program Durability Update for 3E10 vg/eye (Phase 3 Dose)
Date/Time: Monday, February 10, 2025, at 8:00 a.m. ET
Registration: Link
An archived copy of the webcast will be available for up to one year by visiting the “Investors & Media” section of the 4DMT website: https://ir.4dmoleculartherapeutics.com/events.
The presentation from Angiogenesis, Exudation, and Degeneration 2025 will also be available on the 4DMT website: https://4dmoleculartherapeutics.com/pipeline/#posters-and-publications
About 4D-150
4D-150 is a potential backbone therapy that is designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) from the retina with a single, safe, intravitreal injection. 4D-150 utilizes our customized and evolved intravitreal vector, R100, which was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform. 4D-150 is being developed for wet AMD and DME, which both affect millions of patients globally, with the goal of freeing patients from burdensome injections while preserving vision.
About Wet AMD
Wet AMD is a highly prevalent disease with estimated incidence rate of 200,000 new patients per year in the United States. It is estimated that the total prevalence of wet AMD in certain major markets, including the United States and the European Union, and Japan, will be greater than 4 million individuals in the next five years. Wet AMD is a type of macular degeneration in which abnormal blood vessels (macular neovascularization or MNV) grow into the macula, the central area of the retina. As a consequence, MNV causes swelling and edema of the retina, bleeding, and scarring, and causes visual distortion and reduced visual acuity. The proliferation and leakage of abnormal blood vessels is stimulated by VEGF. This process distorts and can potentially destroy central vision and may progress to blindness without treatment.
About 4DMT
4DMT is a late-stage biotechnology company focused on unlocking the full potential of genetic medicines to treat large market diseases in ophthalmology and pulmonology. 4DMT’s proprietary invention platform, Therapeutic Vector Evolution, combines the power of directed evolution with approximately one billion synthetic AAV capsid-derived sequences to invent customized and evolved vectors for use in our wholly owned and partnered product candidates. Our lead program, 4D-150, is a potential backbone therapy that is designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) targeted to the retina with a single, safe, intravitreal injection. Our second core program is 4D-710, which is the first known genetic medicine to demonstrate, in the lungs of people with cystic fibrosis (CF), successful delivery and expression of the CFTR transgene and initial clinical activity signals after aerosol delivery of a gene therapy. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT.
All of our product candidates are in clinical or preclinical development and have not yet been approved for marketing by the FDA or any other regulatory authority. No representation is made as to the safety or effectiveness of our product candidates for the therapeutic uses for which they are being studied.
Learn more at www.4DMT.com and follow us on LinkedIn.
Forward Looking Statements:
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the therapeutic potential, and clinical benefits and market potential of 4DMT’s product candidates, including 4D-150, as well as the plans, announcements, and related timing for the clinical development of and regulatory interactions regarding 4D-150. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including risks and uncertainties that are described in greater detail in the section entitled "Risk Factors" in 4D Molecular Therapeutics’ most recent Quarterly Report on Form 10-Q filed on November 13, 2024 as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent 4D Molecular Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. 4D Molecular Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Contacts:
Media:
Jenn Gordon
dna Communications
Media@4DMT.com
Investors:
Julian Pei
Head of Investor Relations and Corporate Finance
Investor.Relations@4DMT.com
FAQ
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