VX-993 oral / Vertex - LARVOL DELTA

VX24-993-103: Evaluation of Efficacy and Safety of VX-993 for Pain Associated With Diabetic Peripheral Neuropathy (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Trial completion date: May 2026 ➔ Apr 2027 | Trial primary completion date: Apr 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Mapping the Extended Pain Pathway: Human Genetic and Multi-Omic Strategies for Next-Generation Analgesics. (PubMed, Int J Mol Sci) - "The 2025 approval of the selective NaV1.8 blocker suzetrigine for acute pain marked a pivotal advance in analgesic drug development. Yet the subsequent failure of Vertex's next-generation NaV1.8 inhibitor VX993 to demonstrate clinical analgesia underscores enduring challenges in translating mechanistic promise into patient benefit...I propose a practical framework for target validation that integrates: (i) rigorous human genetic support; (ii) cell-type and site-of-action mapping; (iii) human-relevant electrophysiology and PK/PD with verified target engagement; (iv) species-appropriate models; (v) consideration of modality (small molecule, biologic, RNA, targeted protein degradation). Advancing genetically and anatomically aligned targets, tested at the right sites and exposures, offers the best path to genuinely effective, better-tolerated pain therapeutics."

Journal • Review • Genetic Disorders • Immunology • Inflammation • Obesity • Osteoarthritis • Pain • Rheumatology • Targeted Protein Degradation • NAV1 • TRPA1

A Study Evaluating Efficacy and Safety of VX-993 for Acute Pain After a Bunionectomy (clinicaltrials.gov) - P2 | N=367 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Active, not recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ May 2025 | Trial primary completion date: Oct 2025 ➔ May 2025

Trial completion • Trial completion date • Trial primary completion date • Pain

A Study to Evaluate How the Body Processes 14C-VX-993 After a Single Oral Dose (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Active, not recruiting ➔ Completed

Trial completion • Pain

A Study Evaluating Efficacy and Safety of VX-993 for Acute Pain After a Bunionectomy (clinicaltrials.gov) - P2 | N=367 | Active, not recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Recruiting ➔ Active, not recruiting

Enrollment closed • Pain

A Study to Evaluate How the Body Processes 14C-VX-993 After a Single Oral Dose (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Recruiting ➔ Active, not recruiting

Enrollment closed • Pain

A Study to Evaluate How the Body Processes 14C-VX-993 After a Single Oral Dose (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

A Microneurography Study of NaV1.8 Inhibition in Healthy Adults (clinicaltrials.gov) - P1 | N=92 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Recruiting ➔ Completed

Trial completion • Pain

A Study to Evaluate How the Body Processes 14C-VX-993 After a Single Oral Dose (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P1 trial • Pain

Evaluation of the Pharmacokinetic Drug-drug Interactions Between VX-993 and Metformin in Healthy Adults (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Active, not recruiting ➔ Completed

Trial completion • Pain

A Microneurography Study of NaV1.8 Inhibition in Healthy Adults (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Completed ➔ Recruiting | N=40 ➔ 92 | Trial completion date: Jul 2024 ➔ Apr 2025 | Trial primary completion date: Jul 2024 ➔ Mar 2025

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Pain

Evaluation of the Pharmacokinetic Drug-drug Interactions Between VX-993 and Metformin in Healthy Adults (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Recruiting ➔ Active, not recruiting

Enrollment closed • Pain

A Study Evaluating Efficacy and Safety of VX-993 for Acute Pain After a Bunionectomy (clinicaltrials.gov) - P2 | N=355 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

Evaluation of the Pharmacokinetic Drug-drug Interactions Between VX-993 and Metformin in Healthy Adults (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Sep 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Pain

Evaluation of Efficacy and Safety of VX-993 for Pain Associated With Diabetic Peripheral Neuropathy (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

A Study to Evaluate the Relative Bioavailability and Food Effect of a New Tablet Formulation of VX-993 (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Active, not recruiting ➔ Completed

Trial completion • Pain

A Study Evaluating Efficacy and Safety of VX-993 for Acute Pain After a Bunionectomy (clinicaltrials.gov) - P2 | N=355 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P2 trial • Pain

Evaluation of Efficacy and Safety of VX-993 for Pain Associated With Diabetic Peripheral Neuropathy (clinicaltrials.gov) - P2 | N=300 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P2 trial • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

A Study to Evaluate the Relative Bioavailability and Food Effect of a New Tablet Formulation of VX-993 (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Recruiting ➔ Active, not recruiting

Enrollment closed • Pain

Evaluation of the Pharmacokinetic Drug-drug Interactions Between VX-993 and Metformin in Healthy Adults (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

A Study to Evaluate the Relative Bioavailability and Food Effect of a New Tablet Formulation of VX-993 (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

A Phase 1, Open-label Study Evaluating the Pharmacokinetics and Drug-drug Interaction of VX-993 in Healthy Adults (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Active, not recruiting ➔ Completed

Trial completion • Pain

Evaluation of the Pharmacokinetic Drug-drug Interactions Between VX-993 and Metformin in Healthy Adults (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P1 trial • Pain

A Study to Evaluate the Relative Bioavailability and Food Effect of a New Tablet Formulation of VX-993 (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P1 trial • Pain

A Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics, of VX-993 (clinicaltrials.gov) - P1 | N=39 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Active, not recruiting ➔ Completed

Trial completion • Pain