funapide (XEN-402) / Xenon - LARVOL DELTA

Familial Primary Erythromelalgia: Diagnostic and Therapeutic Challenges (EADV 2025) - "Treatment with gabapentin, SSRIs, and aspirin led to slight improvement...Reported options include beta- blockers, tricyclic antidepressants, gabapentin, calcium channel blockers, opioids, lidocaine, mexiletine, and novel NaV1.7 blockers (e.g., funapide, vixotrigine)... Familial primary erythromelalgia is a rare and debilitating condition with limited effective treatments. A multidisciplinary and individualized approach is vital. Psychological support is crucial to improve quality of life and treatment adherence."

Dermatology • Hematological Disorders • Myeloproliferative Neoplasm • Psychiatry • Thrombocytosis • NAV1

Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials. (PubMed, Int J Mol Sci) - "A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN."

Journal • Review • Neuralgia • Pain

Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia. (PubMed, Pain) - "We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker...While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain."

Journal • Neuralgia • Pain

Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review. (PubMed, Pharmaceutics) - "The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series...The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy."

Clinical • Journal • Review • Neuralgia • Pain • Peripheral Neuropathic Pain

[VIRTUAL] Selective Pharmacology Of A Na V 1.7 Antagonist Hydrogel In A Pig Model Of Nerve Block (ASA 2020) - "The effects of FX301 on sensory and motor function following sciatic nerve block were assessed in a validated pain model in pigs, and the pharmacokinetics of funapide release from the hydrogel formulation were measured in plasma and local tissue following injection. 18 young adult pigs were anesthetized, 10 mL of vehicle, FX301 (13 mg/mL), or liposomal bupivacaine (LB) (13.3 mg/mL) was injected via ultrasound-guidance close to the sciatic nerve, and a 5cm surgical incision was created in the ipsilateral hind leg. Prior to the procedure and at 1, 4, 8, 12, 24, 36, 48, and 72h post-procedure, analgesic effect was evaluated by von Frey testing and General Behavior Scoring (GBS), and plasma samples were collected... von Frey testing showed an increase in withdrawal force following FX301 treatment. (Figure 1A ) Withdrawal force (vs vehicle) was significantly higher in pigs treated with FX301 at 36h, but only through 8h with LB. GBS scores were highest in vehicle, indicating..."

Anesthesia • Pain

Xenon Pharmaceuticals reports first quarter 2020 financial results and provides corporate update (GlobeNewswire) - "Flexion Therapeutics, Inc. acquired the global rights to develop and commercialize XEN402...In April 2020, Flexion presented new animal data in an ePoster presentation on the American Society of Regional Anesthesia and Acute Pain website that showed FX301 provided sustained, post-operative analgesic effect with no impairment in motor function compared to liposomal bupivacaine and placebo....A GLP toxicology study with FX301 commenced in April 2020, triggering a $0.5 million milestone payment to Xenon. Flexion anticipates initiating human clinical trials in 2021."

New trial • Preclinical • CNS Disorders • Pain

Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker (Pain) - P=NA, N=04; The ability to induce pain in inherited erythromelalgia (IEM) patients was significantly attenuated by XEN402 compared with placebo; XEN402 increased the time to maximal pain induction and significantly reduced the amount of pain (42 percent less) after induction

Clinical data • Pain

A Study to Evaluate the Safety and Efficacy of Topically Applied TV 45070 Ointment in Patients With Postherpetic Neuralgia (PHN) (clinicaltrials.gov) - P2; N=330; Recruiting; Sponsor: Teva Branded Pharmaceutical Products, R&D Inc.; Trial primary completion date: May 2016 ➔ May 2017

Trial primary completion date • Biosimilar • Pain

Xenon Pharma will offer business, milestone update at Needham Conference (Benzinga) - "Xenon Pharmaceuticals...today announced that Dr. Simon Pimstone...will present a business update, including progress toward milestones, at the Needham Healthcare Conference at 12:50 pm ET on Tuesday, April 12, 2016, in New York City....Xenon's partner Teva Pharmaceutical Industries Ltd. is currently conducting a...Phase 2b clinical trial for TV-45070 in patients with post-herpetic neuralgia....Teva updated its forecast and now expects results in the first half of 2017....Genentech intends to initiate a Phase 2 clinical trial (for GDC-0276) in 2016."

Anticipated conference • Anticipated new P2 trial • Anticipated P2b data • Pain

Xenon Pharmaceuticals reports 2014 financial results and provides corporate update (GlobeNewswire) - "Xenon's partner Teva...is currently conducting a 300-patient...Phase 2b clinical trial for TV-45070 in osteoarthritis. Data from the trial are expected in the third quarter of 2015....Has initiated a Phase 2b clinical trial of TV-45070 in patients with post-herpetic neuralgia, or PHN. The first patient is anticipated to be dosed in March 2015. The anticipated completion date for the Phase 2b clinical trial is mid-2016....The Phase 1 clinical trial (for GDC-0276) has recently been expanded and is expected to complete enrollment in the second half of 2015."

Anticipated P2b data • Anticipated trial completion date • Anticipated trial initiation date • Pain

Flexion Therapeutics and Xenon Pharmaceuticals Announce Flexion’s Acquisition of an Investigational NaV1.7 Inhibitor for the Treatment of Post-Operative Pain (GlobeNewswire, Flexion Therapeutics, Inc.) - "Flexion’s new locally delivered product candidate, FX301, will combine Xenon’s NaV1.7 inhibitor, XEN402, with a novel thermosensitive hydrogel. Acquisition of XEN402 expands Flexion’s portfolio focused on developing and commercializing non-opioid pain management therapies for musculoskeletal conditions....Flexion anticipates initiating FX301 clinical trials in 2021."

Commercial • Preclinical