VX-150 / Vertex - LARVOL DELTA

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 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

State-dependent inhibition of Nav1.8 sodium channels by VX-548, VX-150, A-887826, and LTGO-33: relief of inhibition by depolarization (Neuroscience 2024) - "Relief from A-887826 required weaker depolarizations (midpoint ~+10 mV) and was much faster, so some relief occurred during each AP waveform and accumulated during 20 Hz trains. Interestingly, LTGO-33 required even weaker depolarizations for relief (midpoint near -10 mV) and relief was even faster than for A-887226, but reinhibition between AP waveforms was much faster than for A-887826, so that relief did not accumulate during AP trains at 20 Hz."

Late-breaking abstract • CNS Disorders • Pain • NAV1

State-dependent inhibition of Nav1.8 channels by VX-150 and VX-548. (PubMed, Mol Pharmacol) - "This work describes the potency, selectivity, and state-dependent characteristics of inhibition of Nav1.8 channels by VX-150 and VX-548, compounds that have recently shown efficacy for relief of pain in clinical trials but whose mechanism of interaction with channels has not been described. The results show that the compounds share an unusual property whereby inhibition is relieved by depolarization, demonstrating a state-dependence different than most sodium channel inhibitors."

Journal • Pain • NAV1

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

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

Identification of N-(((1S,3R,5S)-adamantan-1-yl)methyl)-3-((4-chlorophenyl)sulfonyl)benzenesulfonamide as novel Nav1.8 inhibitor with analgesic profile. (PubMed, Bioorg Med Chem Lett) - "Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain."

Journal • Pain • NAV1

A Microneurography Study of NaV1.8 Inhibition in Healthy Adults (clinicaltrials.gov) - P1 | N=40 | 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=40 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P1 trial • Pain

Discovery of a novel series of pyridone amides as NaV1.8 inhibitors. (PubMed, Bioorg Med Chem Lett) - "The molecule VX-150 was initially promising in targeting this channel, but the phase II trials of VX-150 did not show expected pain relief results...One compound, named 2j, stood out with notable activity against the NaV1.8 channel and showed effective pain relief in models of chronic inflammatory pain and neuropathic pain. Our research points to 2j as a strong contender for developing safer pain-relief treatments."

Journal • Neuralgia • Pain • NAV1

A Microneurography (MNG) Study of VX-150 in Healthy Participants (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Vertex Pharmaceuticals Incorporated | Recruiting ➔ Completed

Trial completion • Pain

A Microneurography (MNG) Study of VX-150 in Healthy Participants (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Vertex Pharmaceuticals Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

A Microneurography (MNG) Study of VX-150 in Healthy Participants (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Vertex Pharmaceuticals Incorporated

New P1 trial • Pain

"Did $VRTX discontinue VX-150 (after discontinuing VX-961)? So VX-548 is its third shot at Nav1.8?" (@JacobPlieth)

Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets. (PubMed, Front Pain Res (Lausanne)) - "Despite this, peripheral voltage-gated cation channels retain their promise as therapeutic targets. The way forward may include (i) further structural refinement of K channel activators such as retigabine and ASP0819 to improve selectivity and limit toxicity; use or modification of Na channel blockers such as vixotrigine, PF-05089771, A803467, PF-01247324, VX-150 or arachnid toxins such as Tap1a; the use of Ca channel blockers such as TTA-P2, TTA-A2, Z 944, ACT709478, and CNCB-2; (ii) improving methods for assessing "pain" as opposed to nociception in rodent models; (iii) recognizing sex differences in pain etiology; (iv) tailoring of therapeutic approaches to meet the symptoms and etiology of pain in individual patients via quantitative sensory testing and other personalized medicine approaches; (v) targeting genetic and biochemical mechanisms controlling channel expression using anti-NGF antibodies such as tanezumab or re-purposed drugs such as vorinostat, a..."

Journal • Review • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lymphoma • Neuralgia • Oncology • Pain • Rheumatoid Arthritis • Rheumatology • T Cell Non-Hodgkin Lymphoma • TAP1

[VIRTUAL] Discovery of Hbw-3-80, a Potent, Bioavailable Sodium Channel Nav.1.8 Blocker for Pain (ANA 2021) - "Recently, a number of potent, selective and bioavailable small molecule NaV1.8 blockers, such as VX 150, have demonstrated clinical proof-of-concept with a small molecule investigational treatment targeting NaV1.8 in multiple pain indications including acute pain, neuropathic pain and musculoskeletal pain... We have discovered a novel Sodium Channel NaV.1.8 Blocker HBW-3-80 that has a superior potency, efficacy and safety profile than other known ones. HBW 3-80 provides a valuable clinical candidate for treating acute pain, neuropathic pain and musculoskeletal pain."

Late-breaking abstract • CNS Disorders • Musculoskeletal Pain • Neuralgia • Pain • Peripheral Neuropathic Pain

A Phase 1, Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a highly selective NaV1.8 inhibitor, in Healthy Male Adults. (PubMed, Pain Med) - "Maximum median concentration for the active moiety was 4.30 ug/mL at 4 h post-dose. Results of this proof-of-mechanism study are supportive of the potential of VX-150, a highly selective NaV1.8 channel inhibitor, to treat various pain indications."

Clinical • Journal • P1 data • PK/PD data • Pain

Vertex drops VX-961 to continue search for perfect pain drug (FierceBiotech) - "Vertex has stopped development of VX-961 after getting a look at phase 1 data....Vertex will open a new stage of its search for the perfect NaV1.8 inhibitor when it moves another of VX-150’s siblings into phase 1 later in the first half of 2020. Data from that trial will inform Vertex’s decision about which pain drug to advance into later-stage development."

Discontinued • New P1 trial

40,000 people die each year from narcotic analgesics [Google Translation] (The Korea Economic Daily) - "US-based Heron Teraputix's HTC-011, a non-narcotic painkiller, is waiting for FDA approval after completing Phase III....Vertex Pharmaceuticals' oral non-narcotic painkiller 'VX-150' has the effect of relieving acute pain after surgery. After releasing positive results from Phase II clinical trials last year, he is planning to phase III clinical trials."

New P3 trial • Non-US regulatory