galegenimab (RG6147) / Roche - LARVOL DELTA

Deep Learning-Based Quantification of Vitreous Hyperreflective Foci as a Biomarker for Intraocular Inflammation. (PubMed, Ophthalmol Sci) - P1, P1/2, P2 | "A clinical analysis cohort of 369 patients from the GALLEGO clinical trial (Galegenimab vs. placebo in patients with geographic atrophy, clinical trial ID: NCT03972709)...These findings support automated vHRF quantification as a promising imaging biomarker for inflammation assessment, although further validation in larger and more diverse datasets is needed. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article."

Biomarker • Clinical • Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Inflammation • Macular Degeneration • Macular Edema • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

GATA4-Driven Transcription of HtrA1 Promotes Cellular Senescence in Ménière's Disease and Age-Related Audio-Vestibular Dysfunction. (PubMed, Adv Sci (Weinh)) - "Inhibition of HDAC6 or AAV-mediated HtrA1 overexpression exacerbates MD-like symptoms, whereas inhibition of HtrA1 by Galegenimab ameliorates these phenotypes in mice. In aged mice, GATA4 deletion reduces age-related audio-vestibular deficits and senescence markers. Collectively, our findings establish GATA4 as a critical regulator of cellular senescence and inflammaging in inner ear pathologies, providing promising therapeutic targets for MD and age-related audio-vestibular disorders."

Journal • Inflammation • Otorhinolaryngology • HTRA1

Comment on "Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration". (PubMed, Am J Ophthalmol) - No abstract available

Journal • P2 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • HTRA1

Reply to Comment on Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration. (PubMed, Am J Ophthalmol) - No abstract available

Journal • P2 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • HTRA1

Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration. (PubMed, Am J Ophthalmol) - "Galegenimab administration did not show a difference in mean change in GA area from baseline to Week 72 compared with sham. Inhibition of HtrA1 with a Fab did not slow down GA progression."

Clinical • Journal • P2 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • HTRA1

Targeting both C5 and HTRA1 provides additional rescue effect in NaIO3-induce GA model (ARVO 2024) - "Only 2 complement inhibitors, Syfovre (APL-2) and izervay (avacincaptad pegol), were approved by FDA in 2023. IAR045-001 shows complement cascade and HTRA1 dual blockade activity with superior potency in vitro.IAR045-001 also shows better in vivo efficacy than ARC1905 and galegenimab in a NaIO3-induced GA mouse model.IAR045-001 retains well PK data in rabbit intravitreal study with molecule mass of about 40kD.IAR045-001 are potential to provide better therapeutic efficacy in GA patients."

Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology • HTRA1

Early termination of a Phase 2 study of FHTR2163 in patients with geographic atrophy secondary to age-related macular degeneration (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • P2 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • HTRA1

GALLEGO: A Study Assessing the Safety, Tolerability, and Efficacy of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=360 | Terminated | Sponsor: Genentech, Inc. | Completed ➔ Terminated; The benefit to risk balance did not support further treatment with galegenimab (FHTR2163).

Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study Assessing the Long-Term Safety and Tolerability of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P2 | N=144 | Terminated | Sponsor: Genentech, Inc. | Completed ➔ Terminated; The benefit to risk balance did not support further treatment with FHTR2163.

Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

GALLEGO: A Study Assessing the Safety, Tolerability, and Efficacy of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=360 | Completed | Sponsor: Genentech, Inc. | Terminated ➔ Completed

Trial completion • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study Assessing the Long-Term Safety and Tolerability of Galegenimab (FHTR2163) in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P2 | N=144 | Completed | Sponsor: Genentech, Inc. | Terminated ➔ Completed

Trial completion • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

GALLEGO: A Study Assessing the Safety, Tolerability, and Efficacy of FHTR2163 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=373 | Terminated | Sponsor: Genentech, Inc. | Trial completion date: Dec 2023 ➔ Oct 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Oct 2022; The benefit to risk balance did not support further treatment with FHTR2163.

Trial completion date • Trial primary completion date • Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study Assessing the Long-Term Safety and Tolerability of FHTR2163 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P2 | N=144 | Terminated | Sponsor: Genentech, Inc. | N=360 ➔ 144 | Trial completion date: Dec 2025 ➔ Nov 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Nov 2022; The benefit to risk balance did not support further treatment with FHTR2163.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

GALLEGO: A Study Assessing the Safety, Tolerability, and Efficacy of FHTR2163 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=360 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study Assessing the Long-Term Safety and Tolerability of FHTR2163 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P2 | N=360 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

GALLEGO: A Study Assessing the Safety, Tolerability, and Efficacy of FHTR2163 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2; N=360; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Jun 2024 ➔ Dec 2023; Trial primary completion date: Jun 2024 ➔ Dec 2023

Clinical • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study Assessing the Long-Term Safety and Tolerability of FHTR2163 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P2; N=360; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Dec 2023 ➔ Dec 2025; Trial primary completion date: Dec 2023 ➔ Dec 2025

Clinical • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Phase I Study of the Anti-HtrA1 Antibody-Binding Fragment FHTR2163 in Geographic Atrophy Secondary to Age-Related Macular Degeneration. (PubMed, Am J Ophthalmol) - "FHTR2163, a novel Fab directed against HtrA1, was well tolerated with no DLTs or significant ocular AEs. The molecule when injected intravitreally for 3 doses, showed a sustained pharmacodynamic effect at the maximum tested dose of 20 mg."

Journal • P1 data • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Hematological Disorders • Macular Degeneration • Ophthalmology • Pain • Retinal Disorders • DKK3 • HTRA1

GALLEGO: A Study Assessing the Safety, Tolerability, and Efficacy of RG6147 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2; N=360; Recruiting; Sponsor: Genentech, Inc.; Trial completion date: Mar 2022 ➔ Jun 2024; Trial primary completion date: Mar 2022 ➔ Jun 2024

Clinical • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

Nonclinical Safety Assessment of FHTR2163, An Antigen-Binding Fragment Against HTRA1 for the Treatment of Geographic Atrophy. (PubMed, Toxicol Pathol) - "Observed transient and reversible ocular effects included inflammation and perivascular infiltrates, consistent with an immune response attributed to the administration of heterologous (humanized) protein. Overall, FHTR2163 was well tolerated, and the nonclinical package supported the continued clinical development of FHTR2163 in patients with GA."

Clinical • Journal • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • HTRA1

A Study Assessing the Long-Term Safety and Tolerability of RG6147 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P2; N=360; Recruiting; Sponsor: Genentech, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

A Study Assessing the Long-Term Safety and Tolerability of RG6147 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (clinicaltrials.gov) - P2; N=360; Not yet recruiting; Sponsor: Genentech, Inc.

Clinical • New P2 trial • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders

GALLEGO: A Study Assessing the Safety, Tolerability, and Efficacy of RO7171009 in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2; N=285; Recruiting; Sponsor: Genentech, Inc.

Clinical • New P2 trial

Safety and Tolerability Study of RO7171009 in Participants With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P1; N=28; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed; N=44 ➔ 28

Clinical • Enrollment change • Trial completion