Cardiac contractility (GLS) assessed on ECHO : meaningful improvement in 3 of 3 patients (GLS worsened on ERT natural history study). #4d molecular therapeutics logo trial#
Cardiac biopsy available from one patient in the INGLAXA-2 trial. Quality of life status – Change from baseline at 12 months in Kansas City Cardiomyopathy Questionnaire (KCCQ). Exercise capacity – Change from baseline at 12 months in cardiopulmonary exercise testing (peak VO 2 by CPET). Left ventricular contractility – Change from baseline at 12 months in global longitudinal strain on echocardiography (GLS on ECHO). Assessed FDA-recommended pivotal trial cardiac endpoints in three patients who completed 12 months of follow-up (cut-off date of December 5, 2022) including:. Enrolled six patients, each treated with 1E13 vg/kg of 4D-310 and a prophylactic corticosteroid immunosuppressive regimen. Treated patients in three geographies: INGLAXA-1 (U.S.) and INGLAXA-2 (Taiwan and Australia). Dose-escalation and dose-expansion trial assessing a single intravenous infusion of 4D-310 in a broad and diverse Fabry disease patient population. Following an in-depth investigation in collaboration with world experts in immunology and AAV gene therapy to understand and mitigate aHUS, we are confident that the rituximab and sirolimus immunosuppressive regimen and updated exclusion criteria will mitigate safety risks and potentially further improve patient benefit.” In addition, our focus on patient safety led us to voluntarily pause enrollment on our two INGLAXA trials in January 2023 after observing an aHUS dose-limiting toxicity, and FDA subsequently put the program on clinical hold. We are developing 4D-310 for the treatment of Fabry disease cardiomyopathy, which is the primary cause of death and not addressed by current therapies. “This is our third proprietary vector that has been validated in clinical trials across three different therapeutic areas, which further validates our Therapeutic Vector Evolution platform. “As demonstrated by the positive cardiac outcomes and biopsy biomarker data, these clinical proof-of-concept results with 4D-310 mark another important milestone for 4DMT,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. Data will also be presented at the WORLD Symposium™ 2023 in Orlando, Florida on February 25th, 2023. Following a detailed investigation into the etiology of aHUS, 4DMT is engaging with the FDA to resume enrollment based on updated exclusion criteria and the highly effective rituximab/sirolimus immunosuppressive regimen. Treatment was generally well tolerated, with transient acute aHUS being the only significant adverse event. All three patients with 12 months of follow-up demonstrated improvement on cardiac contractility, exercise capacity and quality of life endpoints. 22, 2023 (GLOBE NEWSWIRE) - 4D Molecular Therapeutics (Nasdaq: FDMT, ‘4DMT’), a clinical-stage biotherapeutics company harnessing the power of directed evolution for targeted genetic medicines, today announced updated interim safety and efficacy data from the two 4D-310 INGLAXA Phase 1/2 clinical trials for Fabry disease cardiomyopathy. Company to host live webcast today at 4:30 p.m. Otherwise, generally well-tolerated with no liver, heart, or dorsal root ganglia (“DRG”) toxicity observed. 
Engaging with FDA to lift clinical hold and resume enrollment with updated exclusion criteria and highly effective rituximab/sirolimus immunosuppressive regimen to reduce risk of atypical hemolytic uremic syndrome (“aHUS”).Cardiac biopsy demonstrated selective and widespread transgene expression within ~50% of cardiomyocytes.
All three patients with 12 months of follow-up demonstrated improvement in multiple FDA-recommended cardiac endpoints at relatively low dose of 1E13 vg/kg.
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