VX-407 / Vertex - LARVOL DELTA

Emerging Therapies in Autosomal Dominant Polycystic Kidney Disease. (PubMed, Kidney360) - "Tolvaptan, a vasopressin V2 receptor antagonist, established cAMP modulation as a disease-modifying strategy but is limited by aquaretic effects and hepatotoxicity risk...Gene-directed therapies aim to restore polycystin dosage, including anti-miR-17 oligonucleotides (e.g., farabursen) and pharmacochaperones that rescue misfolded PC1 and restore trafficking in select PKD1 missense variants (e.g., VX-407)...Metabolic reprogramming is targeted by agents such as metformin, bempedoic acid, GLP-1 receptor agonists, and structured dietary interventions...Collectively, these advances signal a transition toward a layered, mechanism-guided framework in which vasopressin blockade is integrated with metabolic, other signaling, and genotype-specific therapies. As biomarkers and risk stratification tools mature, ADPKD management is poised to become increasingly precise, tolerable, and effective."

Journal • Autosomal Dominant Polycystic Kidney Disease • Gene Therapies • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • IGF1 • MIR17 • PKD1 • PRKD1

THE NEED FOR NOVEL THERAPEUTIC DIRECTIONS IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PATIENT CARE. (PubMed, Clin J Am Soc Nephrol) - "At present, the only drugs approved to slow disease progression are the vasopressin V2-receptor antagonist tolvaptan and, in Italy, the somatostatin analogue octreotide long-acting release for the subset of patients with stage 4 chronic kidney disease...These include not only repurposed pharmacological agents, namely sodium-glucose cotransporter-2 inhibitors, metformin, and glucagon-like peptide-1 receptor agonists, but also innovative therapies, as it is the case for a monoclonal antibody against pregnancy-associated plasma protein-A, microRNA-17 inhibitors, and the polycystin-1 correcting agent VX-407. Dietary interventions, such as caloric restriction and ketogenic diets, are being tested in clinical trials as well, and could complement pharmacotherapy to slow disease progression. Moreover, the rapid advancements in the field of gene therapy for ADPKD suggest that this approach, though as yet only explored at experimental level, could be translated into clinical..."

Journal • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • Gene Therapies • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • MIR17 • PKD1

A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of VX-407 in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Completed ➔ Recruiting | N=24 ➔ 32 | Trial completion date: Sep 2025 ➔ Mar 2026 | Trial primary completion date: Sep 2025 ➔ Mar 2026

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of VX-407 in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Recruiting ➔ Completed

Trial completion • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

AGLOW: Phase 2a Study of VX-407 in Participants With ADPKD Who Have a Subset of PKD1 Gene Variants (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

AGLOW: Phase 2a Study of VX-407 in Participants With ADPKD Who Have a Subset of PKD1 Gene Variants (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P2 trial • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

A Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of VX-407 in Healthy Participants (clinicaltrials.gov) - P1 | N=159 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Active, not recruiting ➔ Completed

Trial completion • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of VX-407 in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

Effects of VX-407 on the Pharmacokinetics of Oral Contraceptives in Healthy Participants (clinicaltrials.gov) - P1 | N=148 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P1 trial • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

Effects of VX-407 on the Pharmacokinetics of Oral Contraceptives in Healthy Participants (clinicaltrials.gov) - P1 | N=148 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

Therapies in autosomal dominant polycystic kidney disease: beyond tolvaptan. (PubMed, Curr Opin Nephrol Hypertens) - "The treatment landscape for ADPKD is rapidly evolving, with multiple innovative therapies advancing toward clinical implementation. Integration of pharmacologic, dietary, and genetic strategies represents a comprehensive approach to modifying disease trajectory. Further large-scale, long-term studies are essential to validate these approaches and optimize individualized patient care."

Journal • Autosomal Dominant Polycystic Kidney Disease • Gene Therapies • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • MIR17

A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of VX-407 in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P1 trial • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

A Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of VX-407 in Healthy Participants (clinicaltrials.gov) - P1 | N=159 | Active, not recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Recruiting ➔ Active, not recruiting | N=119 ➔ 159

Enrollment change • Enrollment closed • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) (Vertex Press Release) - "Vertex is developing small molecule correctors that restore function to the variant polycystin 1 (PC1) protein, with the goal of addressing the underlying cause of ADPKD; Vertex has completed the Phase 1 study of VX-407 in healthy volunteers; Vertex expects to advance VX-407 into a Phase 2 proof-of-concept study this year in patients with a subset of variants in the PKD1 gene, which encodes the PC1 protein, estimated to be up to ~30,000 (or ~10%) of the overall patient population."

New P2 trial • Trial completion • Autosomal Dominant Polycystic Kidney Disease

A Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics (PK) of VX-407 in Healthy Participants (clinicaltrials.gov) - P1 | N=95 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

A Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics (PK) of VX-407 in Healthy Participants (clinicaltrials.gov) - P1 | N=95 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P1 trial • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease