4DMT Presents Injection-Free Subgroup Analyses from 4D-150 Phase 2 PRISM Randomized Dose Expansion Cohort in Wet AMD Patients with Severe Disease Activity & High Treatment Burden at the Clinical Trials at the Summit 2024 Meeting
4D Molecular Therapeutics (Nasdaq: FDMT) presented injection-free subgroup analyses from its Phase 2 PRISM clinical trial evaluating 4D-150 in wet age-related macular degeneration (wet AMD) patients. Results showed that a single dose of 4D-150 maintained or improved visual acuity compared to the standard bimonthly aflibercept injections over 24 weeks. The treatment also resulted in a significant reduction in central subfield thickness (CST). The company plans to present interim results from the Population Extension cohort at the ASRS Annual Meeting on July 17, 2024, and will provide updates on Phase 3 trial designs later in the year.
- Single 3E10 vg/eye dose of 4D-150 maintained or improved visual acuity through Week 24.
- 4D-150 showed a significant reduction in central subfield thickness (CST) compared to aflibercept.
- Injection-free treatment can reduce the treatment burden for severe wet AMD patients.
- Upcoming interim results from the Population Extension cohort to be presented in July 2024.
- Phase 3 clinical trial design updates expected in Q3 2024.
- 4D-150 demonstrated a favorable safety profile in clinical trials.
- The trial results are still interim, and full efficacy and safety are yet to be confirmed.
- The smaller sample size (n=22 for injection-free) may limit the generalizability of the findings.
- Potential delays in Phase 3 clinical trial initiation could affect investor confidence.
Insights
The results of the Phase 2 PRISM trial evaluating 4D-150 in wet AMD patients showcase promising advancements. A single dose of 4D-150 demonstrated stable or improved visual acuity and a significant reduction in central subfield thickness (CST) without requiring supplemental anti-VEGF injections. This is noteworthy because it highlights a potential reduction in treatment burden for patients who typically need frequent injections. Reduced treatment frequency could improve patient adherence and quality of life while maintaining or improving treatment efficacy.
The stability and improvement in visual acuity and CST observed with 4D-150 are substantial findings. Visual acuity is a critical measure, as it directly relates to the patient's ability to perform daily activities. CST stabilization indicates control over the disease’s progression, aligning with the long-term management goals of wet AMD. If these results are replicated in broader trials, 4D-150 could potentially become a game-changer in treating wet AMD.
However, caution is needed as these are interim results from a subgroup analysis. Larger, more diverse populations in subsequent trials will be essential to validate these findings and ensure they are generalizable. Investors should watch the upcoming ASRS presentation and the Phase 3 trial design update closely to gauge the long-term potential and market impact of 4D-150.
The Phase 2 PRISM trial results for 4D-150 have significant implications for 4D Molecular Therapeutics. The data indicate that the treatment could reduce the frequency of injections needed for wet AMD patients, which is a substantial market differentiator. Fewer injections not only improve patient quality of life but also reduce healthcare costs. This could position 4D-150 favorably against existing anti-VEGF therapies, potentially capturing market share from leading products such as Eylea and Lucentis.
From a financial perspective, the reduction in treatment frequency could translate into higher gross margins for 4DMT. If commercialized, 4D-150 could command a premium price due to its improved convenience and similar, if not superior, efficacy compared to current treatments. Investors should also note the upcoming milestones, including the 24-week analysis from the Population Extension cohort and the Phase 3 trial initiation. Positive data from these stages would likely drive stock price appreciation and increase market confidence in 4DMT’s pipeline.
However, investors should remain mindful of the risks inherent in clinical trials. The transition from Phase 2 to Phase 3 is fraught with challenges, including regulatory hurdles and the need for reproducibility of results in a larger patient population. Monitoring these developments will be important for assessing the long-term financial impact on the company.
The reported stabilization and improvement in retinal anatomy and visual acuity with a single dose of 4D-150 in wet AMD patients hold considerable clinical significance. Wet AMD is a leading cause of blindness and current treatments often require frequent intravitreal injections, posing a significant burden on patients and healthcare systems. The potential for a single-dose therapy to maintain or enhance visual outcomes could revolutionize patient management.
The reduction in CST, particularly the mean difference of -31 microns compared to aflibercept, suggests strong anatomical control over fluid accumulation in the retina. This is critical as excessive retinal fluid is a hallmark of disease progression. Clinically, the results imply that 4D-150 may offer a more convenient and equally effective alternative to existing treatments, potentially improving adherence and outcomes in real-world settings.
However, the long-term effects and safety profile will need further validation through extended follow-up and larger scale studies. It's essential to confirm that these initial benefits are sustained over time without unforeseen adverse effects. The upcoming Phase 3 trial will be pivotal in establishing the robustness and reliability of 4D-150's efficacy and safety profile in a larger, more diverse patient population.
- Injection-free subgroup results demonstrated that a single intravitreal dose of 4D-150 without any supplemental anti-VEGF injections resulted in stable mean visual acuity that was equal to or higher than in the standard bimonthly aflibercept control group at all six timepoints through Week 24
- Single intravitreal 3E10 vg/eye dose resulted in sustained reduction and stabilization of mean central subfield thickness (CST) compared to aflibercept at all timepoints
- In the 3E10 vg/eye injection-free subgroup, the mean difference versus aflibercept in CST change from baseline for Weeks 20 and 24 was -31 microns in favor of 4D-150
- Injection-free subgroup analyses reinforce previously reported positive 4D-150 Phase 2 PRISM topline results
- Interim 24-week landmark analysis from Phase 2 PRISM Population Extension cohort evaluating 4D-150 in broader wet AMD population expected to be presented at the American Society of Retina Specialists (ASRS) Annual Scientific Meeting on July 17, 2024
EMERYVILLE, Calif., June 08, 2024 (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 presented supplemental aflibercept injection-free subgroup analyses of the previously reported 24-week landmark results from the randomized Dose Expansion cohort from the Phase 2 PRISM clinical trial evaluating intravitreal 4D-150 in wet age-related macular degeneration (wet AMD) patients with severe disease activity and a high treatment burden. The data were presented today at Clinical Trials at the Summit 2024 in Park City, Utah, by Carl Danzig, M.D., Rand Eye Institute, Deerfield Beach, Florida.
“The injection-free subgroup analyses demonstrate the potential for a single intravitreal 3E10 vg dose of 4D-150 to improve and stabilize retinal anatomy while improving or stabilizing vision in the most severe form of wet AMD with the highest VEGF treatment burden, without the need for any supplemental treatment through 24 weeks in the majority of patients treated,” said Robert Kim, M.D., Chief Medical Officer of 4DMT. “4D-150 to date has shown robust clinical activity with a favorable safety profile, and the data provide additional evidence that 4D-150 has the potential to treat all patients suffering from wet AMD. We look forward to sharing interim results from the Population Extension cohort of PRISM at ASRS in July 2024, and an update on our Phase 3 clinical trial design in the third quarter of 2024.”
Phase 2 PRISM Supplemental Injection-Free Subgroup Analyses
- Stable visual acuity observed through Week 24 in both 4D-150 dose groups (n=22 injection-free patients); BCVA equal to or numerically higher than bimonthly aflibercept (n=10 patients) at all six time points through Week 24
- High dose (3E10 vg/eye; n=12 patients):
- Sustained reduction and stabilization of CST fluctuations compared to bimonthly aflibercept at all six timepoints through Week 24
- The average mean change from baseline in CST at Weeks 20 and 24 was -52.2 mm in the 3E10 vg/eye group and -21.4 in the aflibercept group (mean difference, -30.8 mm)
For additional details, click here to view the scientific presentation, which is available on the 4DMT website: https://4dmoleculartherapeutics.com/pipeline/#posters-and-publications
Upcoming 4D-150 Milestones
- Phase 2 PRISM Population Extension cohort (N=32) in the broader wet AMD patient population:
- Initial interim 24-week landmark analysis expected to be presented at the ASRS Annual Scientific Meeting on July 17, 2024
- Phase 3 planning:
- Update on Phase 3 clinical trial design expected in Q3 2024
- First Phase 3 clinical trial initiation expected in Q1 2025
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 (major markets), and Japan, will be greater than 4 million individuals in the next five years. Wet AMD is a type of macular degeneration where 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 4D-150 for Wet AMD
4D-150 combines our customized and evolved intravitreal vector, R100, and a transgene cassette that expresses both aflibercept and a VEGF-C inhibitory RNAi. This dual-transgene payload inhibits four members of the VEGF angiogenic family of 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; we developed this platform utilizing principles of directed evolution, a Nobel Prize-winning technology. 4D-150 is designed for single, low-dose intravitreal delivery for transgene expression from the retina without significant inflammation.
About 4DMT
4DMT is a leading clinical-stage genetic medicines 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 the Nobel Prize-winning technology, 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 product design, development, and manufacturing engine helps us efficiently create and advance our diverse product pipeline with the goal of revolutionizing medicine with potential curative therapies for millions of patients. Currently, 4DMT is advancing five clinical-stage and two preclinical product candidates, each tailored to address rare and large market diseases in ophthalmology, pulmonology and cardiology. In addition, 4DMT is also advancing programs in CNS through a gene editing partnership. 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 U.S. Food and Drug Administration (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 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 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.
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