4DMT Announces Positive Interim Data from 4D-150 SPECTRA Clinical Trial in DME and Alignment with FDA on Registrational Path
4D Molecular Therapeutics announced positive interim data from Part 1 of the SPECTRA clinical trial evaluating 4D-150 for diabetic macular edema (DME). The data showed that 4D-150 was well tolerated across all dosed DME patients, with no intraocular inflammation observed. The 3E10 vg/eye dose demonstrated significant clinical activity, with a sustained gain in best corrected visual acuity (BCVA) of +8.4 letters and a reduction in central subfield thickness (CST) of -194 µm through Week 32. Additionally, this dose achieved an 86% reduction in injection burden compared to projected on-label aflibercept 2mg Q8W.
The FDA has aligned with 4DMT's proposal for a single Phase 3 trial as a basis for a Biologics License Application (BLA) for 4D-150 in DME. This Phase 3 trial will enroll approximately 300-400 patients, with a primary endpoint of BCVA noninferiority versus on-label aflibercept 2mg.
4DMT plans to present more detailed results and next steps for DME development in a corporate webcast on February 10, 2025. A 52-week interim data update is expected at a scientific conference in mid-2025.
4D Molecular Therapeutics ha annunciato dati interim positivi dalla Fase 1 del trial clinico SPECTRA che valuta 4D-150 per l'edema maculare diabetico (DME). I dati hanno mostrato che 4D-150 è stato ben tollerato da tutti i pazienti affetti da DME a cui è stato somministrato, senza infiammazione intraoculare osservata. La dose di 3E10 vg/occhio ha dimostrato una significativa attività clinica, con un guadagno sostenuto nella migliore acutezza visiva corretta (BCVA) di +8,4 lettere e una riduzione dello spessore del sottocampo centrale (CST) di -194 µm fino alla settimana 32. Inoltre, questa dose ha raggiunto una riduzione dell'86% nel carico di iniezioni rispetto all'aflibercept 2 mg Q8W previsto in etichetta.
La FDA ha concordato con la proposta di 4DMT per un'unica prova di Fase 3 come base per una Domanda di Licenza per Prodotti Biologici (BLA) per 4D-150 nel DME. Questo trial di Fase 3 arruolerà circa 300-400 pazienti, con un obiettivo primario di non inferiorità della BCVA rispetto all'aflibercept 2 mg in etichetta.
4DMT prevede di presentare risultati più dettagliati e i prossimi passi per lo sviluppo del DME in un webcast aziendale il 10 febbraio 2025. Aggiornamenti sui dati interim di 52 settimane sono previsti in una conferenza scientifica a metà del 2025.
4D Molecular Therapeutics anunció datos interinos positivos de la Parte 1 del ensayo clínico SPECTRA que evalúa 4D-150 para el edema macular diabético (DME). Los datos mostraron que 4D-150 fue bien tolerado por todos los pacientes con DME que recibieron la dosis, sin inflamación intraocular observada. La dosis de 3E10 vg/ojo demostró una actividad clínica significativa, con una ganancia sostenida en la mejor agudeza visual corregida (BCVA) de +8.4 letras y una reducción en el grosor del subcampo central (CST) de -194 µm hasta la Semana 32. Además, esta dosis logró una reducción del 86% en la carga de inyecciones en comparación con el aflibercept de 2 mg Q8W previsto en la etiqueta.
La FDA ha alineado con la propuesta de 4DMT para un único ensayo de Fase 3 como base para una Solicitud de Licencia de Productos Biológicos (BLA) para 4D-150 en DME. Este ensayo de Fase 3 inscribirá aproximadamente de 300 a 400 pacientes, con un punto final primario de no inferioridad de la BCVA en comparación con el aflibercept de 2 mg en etiqueta.
4DMT planea presentar resultados más detallados y los próximos pasos para el desarrollo del DME en un webcast corporativo el 10 de febrero de 2025. Se espera una actualización de los datos interinos de 52 semanas en una conferencia científica a mediados de 2025.
4D 분자 치료학이 당뇨병성 황반 부종(DME)에 대한 4D-150를 평가하는 SPECTRA 임상 시험의 1부에서 긍정적인 중간 데이터를 발표했습니다. 데이터에 따르면, 4D-150은 모든 투여된 DME 환자에서 잘 견딜 수 있었으며, 안구 내 염증이 관찰되지 않았습니다. 3E10 vg/눈 용량은 +8.4자라는 보정된 시각적 예리도(BCVA) 향상과 함께 -194 µm의 중심 하부 두께(CST) 감소를 통해 32주 동안 상당한 임상 효과를 보여주었습니다. 또한, 이 용량은 예상된 라벨상의 2mg aflibercept와 비교하여 주사 부담을 86% 줄였습니다.
FDA는 DME에 대한 4D-150의 생물 제품 허가 신청(BLA)을 위한 기초로 단일 3상 시험을 4DMT의 제안에 맞추었습니다. 이 3상 시험은 약 300-400명의 환자를 등록할 예정이며, 주요 목표는 라벨상의 아플리버셉트 2mg에 대한 BCVA 비열성을 목표로 합니다.
4DMT는 2025년 2월 10일 기업 웹캐스트에서 DME 개발에 대한 보다 구체적인 결과와 향후 계획을 발표할 예정입니다. 52주 중간 데이터 업데이트는 2025년 중반에 있을 과학 컨퍼런스에서 예상됩니다.
4D Molecular Therapeutics a annoncé des données intermédiaires positives de la Partie 1 de l'
La FDA s'est alignée sur la proposition de 4DMT pour un essai de Phase 3 unique comme base pour une Demande de Licence Biologique (BLA) pour 4D-150 dans le DME. Cet essai de Phase 3 inscrira environ 300 à 400 patients, avec un objectif principal de non-infériorité de la BCVA par rapport à l'aflibercept 2 mg en étiquette.
4DMT prévoit de présenter des résultats plus détaillés et les prochaines étapes du développement du DME lors d'un webcast d'entreprise le 10 février 2025. Une mise à jour des données intermédiaires de 52 semaines est attendue lors d'une conférence scientifique à la mi-2025.
4D Molecular Therapeutics hat positive Zwischenresultate aus Teil 1 der SPECTRA-Studie veröffentlicht, die 4D-150 bei diabetischem Makulaödem (DME) bewertet. Die Daten zeigten, dass 4D-150 von allen dosierten DME-Patienten gut toleriert wurde, ohne dass interne Entzündungen beobachtet wurden. Die Dosis von 3E10 vg/Auge zeigte eine signifikante klinische Aktivität, mit einem nachhaltigen Gewinn der besten korrigierten Sehschärfe (BCVA) von +8,4 Buchstaben und einer Reduktion der zentralen Unterfelddicke (CST) um -194 µm bis zur Woche 32. Darüber hinaus erzielte diese Dosis eine Reduktion der Injektionsbelastung um 86% im Vergleich zum vorgesehenen Aflibercept 2 mg Q8W.
Die FDA hat sich mit dem Vorschlag von 4DMT für eine einzelne Phase-3-Studie als Grundlage für einen Antrag auf Biologika-Lizenz (BLA) für 4D-150 bei DME abgestimmt. Diese Phase-3-Studie wird voraussichtlich etwa 300-400 Patienten aufnehmen, mit einem primären Endpunkt der Nichtunterlegenheit der BCVA im Vergleich zu Aflibercept 2 mg in der Etikettierung.
4DMT plant, am 10. Februar 2025 in einem Unternehmens-Webcast detailliertere Ergebnisse und die nächsten Schritte zur Entwicklung von DME vorzustellen. Ein Update zu den Zwischenresultaten nach 52 Wochen wird im mittleren Jahr 2025 auf einer wissenschaftlichen Konferenz erwartet.
- 4D-150 demonstrated sustained gain of BCVA (+8.4 letters) and reduction in CST (-194 µm) through Week 32.
- The 3E10 vg/eye dose achieved an 86% reduction in injection burden compared to projected on-label aflibercept 2mg Q8W.
- FDA alignment on a single Phase 3 trial for 4D-150 in DME, facilitating the BLA submission.
- None.
Insights
The interim data from the SPECTRA trial demonstrates compelling efficacy and safety metrics for 4D-150 in treating diabetic macular edema (DME). The 3E10 vg/eye dose achieved notable improvements with a +8.4 letter gain in best corrected visual acuity and a substantial -194 µm reduction in central subfield thickness through Week 32. Most remarkably, the treatment reduced injection burden by
The absence of intraocular inflammation and successful completion of steroid tapering by all patients indicates an excellent safety profile. These results suggest 4D-150 could revolutionize DME treatment by potentially replacing frequent injections with a single dose providing multi-year VEGF inhibition.
The FDA's alignment on a single Phase 3 trial pathway for DME represents a significant regulatory breakthrough. This streamlined approach, leveraging data from both DME and wet AMD trials, could accelerate the path to market. The agency's acceptance of a 300-400 patient trial with BCVA noninferiority endpoint versus aflibercept is particularly favorable from a development timeline and cost perspective.
The removal of the requirement for SPECTRA Part 2 and immediate progression to Phase 3 signals strong regulatory confidence in the current data package. This expedited pathway could potentially reduce the development timeline by 12-18 months, representing substantial value creation potential for shareholders.
With approximately one million DME patients in the U.S. alone, 4D-150's market opportunity is substantial. The
The therapy's demonstrated efficacy combined with the simplified treatment regimen could command premium pricing and drive strong market penetration. The streamlined regulatory pathway reduces development costs and accelerates time to market, potentially leading to earlier revenue generation than previously anticipated.
- Across all DME patients dosed to date, 4D-150 continues to be well tolerated with no intraocular inflammation observed at any timepoint or dose level
- 3E10 vg/eye demonstrated strong signals of clinical activity with sustained gain of BCVA of +8.4 letters and reduction of CST of -194 µm from baseline through Week 32
- 3E10 vg/eye achieved an
86% reduction in injection burden vs. projected on-label aflibercept 2mg Q8W and dose response with61% reduction vs. 1E10 vg/eye, with 0.6 mean supplemental injections per patient through Week 32 - FDA aligned with proposed single Phase 3 clinical trial being acceptable for the basis of a BLA submission for 4D-150 in DME, based on review of data from SPECTRA and PRISM (wet AMD) clinical trials to date and planned global Phase 3 clinical development program for wet AMD
EMERYVILLE, Calif., Jan. 10, 2025 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company), a leading clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat large market diseases, today announced positive topline interim data from Part 1 of the SPECTRA clinical trial evaluating 4D-150 in diabetic macular edema (DME) and alignment with the U.S. Food and Drug Administration (FDA) on registrational pathway for 4D-150 in DME.
“The promising initial safety and clinical activity data of 4D-150 in DME patients, together with the promising results in wet age-related macular degeneration (wet AMD), reinforces the potential applicability of 4D-150 across multiple VEGF-driven retinal diseases,” said Carlos Quezada-Ruiz, M.D., FASRS, SVP, Therapeutic Area Head, Ophthalmology. “4D-150 represents a potentially transformative new therapeutic option for the approximately one million DME patients in the U.S. alone. 4D-150 has the potential to set a new backbone therapy providing multi-year sustained VEGF inhibition in the retina with a single, safe, intravitreal injection. If approved, 4D-150 could significantly reduce the need for frequent bolus injections and address the current real-world challenge of patient adherence to therapy, thereby leading to better disease management and vision outcomes.”
Clinical Trial Design & Interim Data from 4D-150 SPECTRA Part 1 Clinical Trial (Data Cutoff of December 13, 2024):
- Objectives: Evaluate safety and tolerability and identify dose level for further evaluation
- Utilized stringent supplemental aflibercept criteria and enrolled patients with high central subfield thickness (CST) to maximize patient safety and assess initial clinical activity
- Study Population:
- 22 patients enrolled across 3 dose levels: 3E10 vg/eye (n=9), 1E10 vg/eye (n=12), 5E9 vg/eye (n=1); 1 patient in 1E10 vg/eye arm terminated the study due to death unrelated to 4D-150, prior to completion of a post-baseline assessment
- Safety (n=21):
- 4D-150 was well tolerated with no intraocular inflammation at any timepoint
- All patients completed the 16-week topical corticosteroid taper on schedule and remained completely off steroids
- No hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions
- 4D-150 was well tolerated with no intraocular inflammation at any timepoint
- Efficacy Results Through 32 Weeks:
- 3E10 vg/eye arm:
- Sustained gain of best corrected visual acuity (BCVA) of +8.4 letters
- Sustained reduction of CST, as measured by optical coherence tomography (OCT), of -194 µm
- Supplemental injections: Post-aflibercept loading doses (3), 3E10 vg/eye achieved substantially fewer supplemental injections compared to 1E10 vg/eye and projected on-label aflibercept 2mg Q8W:
- Mean injections per patient:
- 3E10 vg/eye: 0.6, 1E10 vg/eye: 1.4, projected on-label aflibercept 2mg Q8W: 4.0
- 3E10 vg/eye demonstrated a reduction of
61% vs. 1E10 vg/eye - 3E10 vg/eye demonstrated a reduction of
86% vs. projected on-label aflibercept 2mg Q8W
- 0-1 injections:
- 8 of 9 overall (3E10 vg/eye) vs. 5 of 10 (1E10 vg/eye, 1 patient missed Week 24-32 visits)
- Injection-free:
- 5 of 9 overall (3E10 vg/eye) vs. 2 of 10 overall (1E10 vg/eye)
- 5 of 8 in patients treated per protocol (3E10 vg/eye)
- Mean injections per patient:
- 3E10 vg/eye arm:
- Results to be presented in a corporate webcast on February 10, 2025
- 52-week interim data update expected at a scientific conference in mid-2025
- Data slides can be found on the “Investors” section of the 4DMT website at https://ir.4dmoleculartherapeutics.com/
4D-150 DME Phase 3 Regulatory Update & Next Steps
- 3E10 vg/eye has been selected as the Phase 3 dose
- Based on data generated to date for 4D-150 in both the SPECTRA and PRISM clinical trials, FDA is aligned that a single Phase 3 clinical trial, combined with data from the two planned Phase 3 clinical trials in the 4FRONT wet AMD program, would be acceptable as the basis of a BLA submission for 4D-150 in DME
- Per FDA feedback, the Company may proceed to Phase 3 (SPECTRA Part 2 no longer needed) and is aligned with key design elements of a Phase 3 clinical trial with approximately 300-400 patients total with a primary endpoint of BCVA noninferiority vs. on-label aflibercept 2mg (5 loading doses and Q8W), and revised supplemental injection criteria (less stringent compared to Part 1 SPECTRA, in line with prior successful Phase 3 DME clinical trials)
- Next steps for DME development to be presented in a corporate webcast on February 10, 2025
“The highly differentiated tolerability and promising clinical activity profile to date for 4D-150, and supportive feedback we received from the FDA in both wet AMD and DME, is a testament to 4D-150’s differentiated product design based on our proprietary R100 vector and our strong team, including our global Ophthalmology Advisory Board,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “The alignment with the FDA on the design and path forward for a single Phase 3 trial in DME is a positive step forward in our ability to realize 4D-150’s potential as a pipeline-in-a-product, which may unlock DME as a second large market indication shortly after wet AMD."
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 DME
DME, or diabetic macular edema, is a complication of diabetic retinopathy and is a highly prevalent disease with significant unmet medical need and poor treatment adherence. It is estimated that there are approximately one million individuals with DME in the U.S. according to published data. DME is characterized by inflammation swelling in the macula due to leakage from blood vessels, which can lead to vision loss. DME is typically treated with intravitreal anti-VEGF agents administered approximately every 4-12 weeks, although patient compliance with therapy is poor and results in high unmet medical need.
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, 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:
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Inizio Evoke Comms
Media@4DMT.com
Investors:
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Head of Investor Relations and Corporate Finance
Investor.Relations@4DMT.com
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