sefaxersen (RG6299) / Ionis, Roche - LARVOL DELTA

Suppression of complement alternative pathway by monthly dosing of sefaxersen, a novel antisense oligonucleotide therapy in development for IgAN (ERA 2025) - No abstract available

Glomerulonephritis • IgA Nephropathy

Inhibiting the alternative pathway of complement by reducing systemic complement factor B: Randomized, double-blind, placebo-controlled phase 1 studies with Sefaxersen. (PubMed, Immunobiology) - "The long duration of lowering of FB levels following the last dose supports monthly dosing in future clinical trials. These clinical results support the ongoing Phase 2 development for geographic atrophy secondary to age-related macular degeneration and Ph 2/3 development for IgA nephropathy."

Clinical • Journal • P1 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Macular Degeneration • Ophthalmology • Renal Disease • Retinal Disorders • CFB

Inhibition of the Complement Alternative Pathway Attenuates Hemolysis and Preserves Renal Function in a Mouse Model of Sickle Cell Disease (ASH 2024) - "Notably, ASO factor B (alone or in combination) markedly decreased RBC opsonization by C3/C3b (p<0.001)...Improvement in renal function is particularly significant, as renal impairment is a common and severe complication in SCD, impacting patient morbidity and mortality. These findings support further exploration of complement-targeted therapies to ameliorate hemolysis and preserve organ function in SCD patients."

Preclinical • Genetic Disorders • Hematological Disorders • Renal Disease • Sickle Cell Disease • CD55 • CD59 • KIM1 • LCN2

Phase II Results of an Investigational RNA Therapeutic to Complement Factor B, IONIS-FB-LRx, for Treatment of IgA Nephropathy (KIDNEY WEEK 2024) - P2, P3 | "IONIS-FB-LRx met primary endpoints in patients with biopsy-confirmed IgAN. This Ph2 open-label study provides consistent clinical evidence supporting ongoing Ph3 study of IONIS-FB-LRx /RO7434656 to reduce the progression of IgAN (NCT05797610)."

Late-breaking abstract • P2 data • Glomerulonephritis • IgA Nephropathy • Renal Disease • CFB

GOLDEN STUDY: A Study to Assess Safety and Efficacy of Multiple Doses of IONIS-FB-LRx in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=332 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

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

IONIS-FB-LRx, An Antisense Oligonucleotide to Complement Factor B for Treatment of IgA Nephropathy. (ERA-EDTA 2024) - P2, P3 | "This Ph2 open-label study provides continuing clinical evidence that IONIS-FB-L Rx reduces complement levels and proteinuria in patients with IgAN, supporting Ph3 development (NCT05797610) to determine the potential of IONIS-FB-L Rx to reduce the progression of IgAN."

Glomerulonephritis • IgA Nephropathy • Renal Disease • CFB

A Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Participants With Primary IgA Nephropathy (clinicaltrials.gov) - P2 | N=23 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Glomerulonephritis • IgA Nephropathy • Renal Disease

IMAGINATION: A GLOBAL PHASE 3 TRIAL OF RO7434656, AN ANTISENSE OLIGONUCLEOTIDE INHIBITOR OF COMPLEMENT FACTOR B, IN IGA NEPHROPATHY (ISN-WCN 2024) - P2, P3 | "The unique antisense modality and long tissue half-life of RO7434656 enables Q4W SC administration to inhibit the alternative complement pathway. IMAGINATION aims to evaluate the efficacy and safety of RO7434656 in adults with IgAN using a broad range of assessments over 105 weeks. This abstract was also submitted and accepted for presentation at ASN Kidney Week 2023."

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Renal Disease • CFB

A Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Participants With Primary IgA Nephropathy (clinicaltrials.gov) - P2 | N=23 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Phase classification: P2a ➔ P2 | Trial completion date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: Dec 2023 ➔ Apr 2024

Phase classification • Trial completion date • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

GOLDEN STUDY: A Study to Assess Safety and Efficacy of Multiple Doses of IONIS-FB-LRx in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=332 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc.

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

An Exploratory Trial of an Investigational RNA Therapeutic, IONIS-FB-LRx, for Treatment of IgA Nephropathy: New Interim Results (KIDNEY WEEK 2023) - P2a, P3 | "This Ph2 open-label study provides continuing clinical evidence that IONIS-FB-LRx, reduces complement levels and proteinuria in patients with IgAN, supporting Ph3 development (NCT05797610) to determine the potential of IONIS-FB-LRx to reduce the progression of IgAN."

Glomerulonephritis • IgA Nephropathy • Renal Disease • CFB

IMAGINATION: A Global Phase 3 Trial of RO7434656, an Antisense Oligonucleotide Inhibitor of Complement Factor B, in IgA Nephropathy (KIDNEY WEEK 2023) - P2a, P3 | "The unique antisense modality and long tissue half-life of RO7434656 enables Q4W SC administration to inhibit the alternative complement pathway. IMAGINATION aims to evaluate the efficacy and safety of RO7434656 in adults with IgAN using a broad range of assessments over 105 weeks."

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Renal Disease • CFB

A Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Participants With Primary IgA Nephropathy (clinicaltrials.gov) - P2a | N=23 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • IgA Nephropathy • Renal Disease

IMAGINATION: A Study to Evaluate the Efficacy and Safety of RO7434656 in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression (clinicaltrials.gov) - P3 | N=428 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • IgA Nephropathy • Renal Disease

IMAGINATION: A Study to Evaluate the Efficacy and Safety of RO7434656 in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression (clinicaltrials.gov) - P3 | N=428 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

GOLDEN STUDY: A Study to Assess Safety and Efficacy of Multiple Doses of IONIS-FB-LRx in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=330 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2024 ➔ Jul 2024 | Trial primary completion date: Jan 2024 ➔ Apr 2024

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

Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway. (PubMed, Immunol Rev) - "This review explains key concepts of RNA and DNA targeting and discusses assets in clinical development for the treatment of diseases driven by the alternative pathway, including the RNA-targeting therapeutics ALN-CC5, ARO-C3, and IONIS-FB-LRX, and the gene therapies GT005 and HMR59. These therapies are but the spearhead of potential drug candidates that might revolutionize the field in coming years."

Journal • Review • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Gene Therapies • Hematological Disorders • Inflammation • Macular Degeneration • Ophthalmology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Retinal Disorders

An Exploratory Trial of an Investigational RNA Therapeutic, IONIS-FB-LRx, for Treatment of IgA Nephropathy (KIDNEY WEEK 2022) - P2a | "All subjects completed the study (wk 29). Conclusion This Ph 2 open label study provides initial clinical evidence that IONIS-FB- L Rx, reduces complement and proteinuria in patients with IgAN, supporting further development to determine the potential of IONIS-FB-L Rx to reduce the progression of IgA nephropathy."

Glomerulonephritis • IgA Nephropathy • Renal Disease • CFB

GOLDEN STUDY: A Study to Assess Safety and Efficacy of Multiple Doses of IONIS-FB-LRx in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD) (clinicaltrials.gov) - P2 | N=330 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial completion date: Oct 2022 ➔ Jan 2024 | Trial primary completion date: Oct 2022 ➔ Jan 2024

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

A Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Participants With Primary IgA Nephropathy (clinicaltrials.gov) - P2a | N=25 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | N=10 ➔ 25

Enrollment change • Glomerulonephritis • IgA Nephropathy • Renal Disease

Baseline Characteristics in the Phase 2 GOLDEN Study of IONIS-FB-LRx, an Investigational Antisense Oligonucleotide Designed to Treat AMD-Associated Geographic Atrophy (ASRS 2022) - No abstract available

P2 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration

A Study to Evaluate the Effectiveness and Safety of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Adult Participants With Primary IgA Nephropathy (clinicaltrials.gov) - P2a; N=10; Recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Trial completion date: Jan 2021 ➔ Dec 2023; Trial primary completion date: Jan 2021 ➔ Dec 2023

Trial completion date • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

[VIRTUAL] Systemic Antisense Oligonucleotide Inhibition of Complement Factor B for Treatment of Geographic Atrophy: Results of a Placebo-controlled Phase 1 Dose-Escalation Study (ARVO 2021) - P2 | "IONIS-FB-LRX, is a novel antisense oligonucleotide drug, administered subcutaneously with a potential for monthly dosing. This first-in-human IONIS-FB-LRx study found the antisense drug to exhibit robust lowering of systemic FB and excellent safety profile. Based on these data, a Phase 2 double-masked, randomized placebo- controlled trial (N=330), the GOLDEN study, is currently underway to determine the potential of systemic IONIS-FB-L Rx in reducing progression of GA (NCT03815825)."

Clinical • P1 data • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Ophthalmology • Retinal Disorders • CFB

[VIRTUAL] Systemic administration of an antisense oligonucleotide, IONIS-FB-LRx for treatment of geographic atrophy (EURETINA 2020) - P2 | "IONIS-FB-LRX, is a novel antisense oligonucleotide drug, administered subcutaneously with a potential for monthly dosing. This Phase 1 study demonstrated that IONIS-FB-LRx provided a dose dependent reduction in FB and the ACP activity and was safe, supporting further development. Based on these data, a Phase 2 double-masked, randomized placebo-controlled trial (the GOLDEN study) is currently underway to determine the potential of systemic IONIS-FB-LRx in reducing progression of GA (NCT03815825)."

Age-related Macular Degeneration • Complement-mediated Rare Disorders • Dry Age-related Macular Degeneration • Hematological Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders

Newly added product (Ionis Pharmaceuticals Press Release) - P2, Age-related Macular Degeneration

Pipeline update • Age-related Macular Degeneration • Ophthalmology