resiniferatoxin (GRT7039) / Grunenthal, Shionogi - LARVOL DELTA

Open-label Trial to Check the Safety and Tolerability of RTX-GRT7039 Injections for Pain Associated With Osteoarthritis of the Knee (clinicaltrials.gov) - P3 | N=930 | Active, not recruiting | Sponsor: Grünenthal GmbH | Trial completion date: Aug 2025 ➔ May 2025 | Trial primary completion date: Aug 2025 ➔ May 2025

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology

Efficacy and Safety of RTX-GRT7039 in Adult Subjects With Knee Osteoarthritis (clinicaltrials.gov) - P3 | N=450 | Completed | Sponsor: Grünenthal GmbH | Active, not recruiting ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

An Evaluation of the Efficacy, Pharmacokinetics and Safety, of the Transient Receptor Potential Vanilloid 1 (TRPV1) Agonist RTX-GRT7039 – a Placebo-controlled Study in Patients with Osteoarthritis Knee Pain (ACR Convergence 2024) - "RTX-GRT7039 is an investigational medicinal product containing the active pharmacological agent, resiniferatoxin (RTX), a potent agonist of TRPV1 and a direct-acting neuronal analgesic that selectively targets and deactivates TRPV1-expressing nociceptors.The aim of this trial was to evaluate the efficacy and safety of a single intra-articular (IA) injection of RTX-GRT7039 in knee OA. This phase II RCT (P03, Part 2) enrolled patients with a baseline VAS pain score >40mm (0-100mm) on motion for average joint pain in the target knee during the last 2 days, with or without analgesic medication, and Kellgren-Lawrence Grade 2-4.Forty patients (25 females, 15 males; mean age of 65.5 years) were randomized and treated with RTX-GRT7039 2 mg [n=11] or 4 mg [n=10; all RTX-GRT7039 doses are presented as equivalent to Euphorbia resinifera latex in the injectate solution] administered consecutively (within 1 minute) to IA local anesthetic (LA; ropivacaine, 5mL, 0.5%); or..."

Clinical • PK/PD data • Anesthesia • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • TRPV1

Comparison of a Single RTX-GRT7039 and Placebo Intra-articular Injection for Pain Associated With Osteoarthritis of the Knee (clinicaltrials.gov) - P3 | N=450 | Completed | Sponsor: Grünenthal GmbH | Active, not recruiting ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

Open-label Trial to Check the Safety and Tolerability of RTX-GRT7039 Injections for Pain Associated with Osteoarthritis of the Knee (clinicaltrials.gov) - P3 | N=930 | Active, not recruiting | Sponsor: Grünenthal GmbH | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology

Targeting the TRPV1 pain pathway in osteoarthritis of the knee. (PubMed, Expert Opin Ther Targets) - "Capsaicin and resiniferatoxin have provided proof-of-concept for the modulation of TRPV1 activity in KOA. Intra-articular administration of TRPV1 agonists enables direct delivery to target nerve terminals in the knee, offering a potentially transformative approach for the management of pain associated with KOA. Here, we explore the advances in understanding innervation of the knee joint in KOA, the role of TRPV1-expressing neurons and progress in developing TRPV1 modulators for KOA."

Journal • Review • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • TRPV1

Safety and Analgesic Effect of the TRPV1 Agonist RTX-GRT7039 in Osteoarthritis Knee Pain (PAINWeek 2024) - "Background: Transient receptor potential vanilloid 1 (TRPV1) expression plays an important role in neuropathic and inflammatory pain and pain sensitization.1,2 TRPV1-expressing neurons are present within the synovium and subchondral bone of the human osteoarthritis (OA) knee joint, making TRPV1 a potential treatment target for OA-related knee pain.2-4 RTX-GRT7039 is an intra-articular (IA) injection comprising resiniferatoxin (RTX), a potent and selective agonist of TRPV1 in injectate solution.5,6 RTX is a direct-acting neuronal analgesic that selectively targets and deactivates TRPV1-expressing nociceptors, which can durably suppress knee OA pain.7,8 Preclinical animal models of OA have demonstrated reduced pain behaviors and long-term pain relief following IA administration of RTX.9,10Purpose/Objectives: The purpose of this study was to evaluate the safety, tolerability, and potential efficacy of RTX-GRT7039, a resiniferatoxin-based intra-articular injection, in..."

Clinical • CNS Disorders • Musculoskeletal Pain • Pain • TRPV1

First-in-Human Study of the TRPV1 Agonist RTX-GRT7039 for Knee Osteoarthritis Pain (PAINWeek 2024) - "Background: Transient receptor potential vanilloid 1 (TRPV1) expression plays an important role in neuropathic and inflammatory pain and pain sensitization.1,2 TRPV1-expressing neurons are present within the synovium and subchondral bone of the human osteoarthritis (OA) knee joint, making TRPV1 a potential treatment target for OA-related knee pain.2-4 RTX-GRT7039 is an intra-articular (IA) injection comprising resiniferatoxin (RTX), a potent and selective agonist of TRPV1 in injectate solution.5,6 RTX is a direct-acting neuronal analgesic that selectively targets and deactivates TRPV1-expressing nociceptors, which can durably suppress knee OA pain.7,8 Preclinical animal models of OA have demonstrated reduced pain behaviors and long-term pain relief following IA administration of RTX.9,10Purpose/Objectives: The study aimed to evaluate the safety and exploratory efficacy of intra-articular (IA) injections of RTX-GRT7039 in individuals with chronic knee osteoarthritis (OA)..."

P1 data • CNS Disorders • Musculoskeletal Pain • Pain • TRPV1

Comparison of a Single RTX-GRT7039 and Placebo Intra-articular Injection for Pain Associated With Osteoarthritis of the Knee (clinicaltrials.gov) - P3 | N=450 | Active, not recruiting | Sponsor: Grünenthal GmbH | Trial completion date: Feb 2024 ➔ Aug 2024 | Trial primary completion date: Feb 2024 ➔ Aug 2024

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology

Efficacy and Safety of RTX-GRT7039 in Adult Subjects With Knee Osteoarthritis (clinicaltrials.gov) - P3 | N=450 | Active, not recruiting | Sponsor: Grünenthal GmbH | Trial completion date: Feb 2024 ➔ Nov 2024 | Trial primary completion date: Feb 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology

PRELIMINARY EVALUATION OF THE SAFETY AND ANALGESIC EFFICACY OF THE TRPV1 AGONIST RTX-GRT7039 IN KNEE OSTEOARTHRITIS: A RANDOMISED, DOUBLE-BLIND, EXPLORATORY PHASE II STUDY (EULAR 2024) - "Background: RTX-GRT7039 (resiniferatoxin; RTX), is a potent and selective agonist of the transient receptor potential vanilloid 1 (TRPV1) being developed for treatment of pain related to knee osteoarthritis (KOA)...Seven SAEs were reported in 6 subjects [2 subjects (0.5 mg), 3 subjects (2 mg) 1 subject (placebo)], none of which were considered to be related to the IMP or ropivacaine... This exploratory trial indicates that single IA doses of RTX (0.5 mg and 2 mg; Euphorbia resinifera latex in the injectate solution) have the potential to deliver meaningful pain relief for patients with knee OA. Analgesic onset occurred within one week of administration and was evident for at least 3 months during the follow-up period. Injection site pain was expected and transient."

Clinical • P2 data • Back Pain • Immunology • Infectious Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • TRPV1

Open-label Trial to Check the Safety and Tolerability of RTX-GRT7039 Injections for Pain Associated With Osteoarthritis of the Knee (clinicaltrials.gov) - P3 | N=930 | Active, not recruiting | Sponsor: Grünenthal GmbH | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Osteoarthritis • Pain • Rheumatology

Evaluation of the safety and analgesic effect of the TRPV1 agonist RTX-GRT7039 – an open-label, single dose study in patients with chronic osteoarthritic knee joint pain (Study P02) (OARSI 2024) - "Purpose (the aim of the study): RTX-GRT7039 (RTX), previously known as MTX-071, is a potent and selective agonist of the transient receptor potential vanilloid 1 (TRPV1). Activation of TRPV1-expressing neurones is followed by reversible defunctionalisation of the peripheral terminals of C- and A-delta nerve fibres that can lead to prolonged analgesia"

Clinical • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • TRPV1

Preliminary evaluation of the safety and analgesic effect of the TRPV1 agonist RTX-GRT7039 – an open-label, first-in-human study in patients with chronic pain due to knee osteoarthritis (Study P01) (OARSI 2024) - "Purpose (the aim of the study): RTX-GRT7039 (resiniferatoxin; RTX), is a potent and selective agonist of the transient receptor potential vanilloid 1 (TRPV1). Activation of TRPV1-expressing neurones, by RTX, is followed by reversible defunctionalisation of the peripheral terminals of C- and A-delta nerve fibres that can lead to prolonged analgesia."

Clinical • P1 data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • TRPV1

Grünenthal’s resiniferatoxin receives Breakthrough Therapy Designation from U.S. FDA for pain associated with osteoarthritis of the knee (PRNewswire) - "Grünenthal today announced that its investigational non-opioid medicine resiniferatoxin (RTX), currently undergoing clinical Phase III development, received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for pain associated with osteoarthritis (OA) of the knee. The decision is based on clinical phase I and II data indicating significant pain relief and a favourable safety profile."

Breakthrough therapy designation • CNS Disorders • Osteoarthritis • Pain

Grünenthal GmbH: Grünenthal reports record revenue and profit in 2022 full-year results and strong pipeline progress (news with additional features) (Yahoo News) - "Grünenthal...released its 2022 full-year results, announcing record revenue and adjusted EBITDA....Grünenthal further advanced the investigational medicines in its research pipeline. A key priority is the development of Resiniferatoxin (RTX). The investigational treatment is being developed for treating pain in patients with knee osteoarthritis and entered clinical phase III in August 2022. A readout of the data is expected in the second half of 2024. The phase III programme aims to enable market authorisation in the E.U., U.S. and Japan by 2025/2026."

European regulatory • Japanese regulatory • NDA • P3 data • CNS Disorders • Osteoarthritis • Pain

Grünenthal starts Phase III trials for resiniferatoxin in osteoarthritis-related pain (PRNewswire) - "Grünenthal announced today that the company has enrolled the first patient in its global clinical Phase III programme for resiniferatoxin (RTX)....Grünenthal's Phase III programme will include more than 1800 patients with knee osteoarthritis who have exhausted available treatment options and still suffer from moderate to severe pain. Grünenthal will conduct three trials across approximately 200 sites across Europe, the US, Latin America, South Africa and Japan to investigate the efficacy and safety of intra-articular injections of RTX in adults. The efficacy endpoints observed in the trials mainly focus on an improvement in the pain and physical function score in the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index from baseline up to 52 weeks. Upon completion, the Phase III programme is intended to enable marketing approval for RTX in the EU, the US, and Japan. Grünenthal aims to submit a new drug application..."

Enrollment open • Launch US • NDA • CNS Disorders • Osteoarthritis • Pain

Grünenthal and NovaQuest Enter Agreement to Advance the Resiniferatoxin Global Phase III Program in Osteoarthritis (Businesswire) - "Grünenthal and NovaQuest announced today that they have entered an agreement to advance the global clinical Phase III programme of Grünenthal's asset resiniferatoxin (RTX)....The Phase III trials will investigate the efficacy, safety and tolerability of RTX in patients with pain associated with osteoarthritis of the knee. The trials will start in 2022 and are designed to meet the requirements for marketing approval in the EU, the US, and Japan....Under the terms of the agreement, NovaQuest will reimburse Grünenthal’s investments into the clinical phase III programme of RTX and share the clinical development and approval risks with Grünenthal. In case of successful development and marketing approval, NovaQuest receives one-time payments or milestones and revenue-based payments over the course of the commercialization."

Licensing / partnership • New P3 trial • CNS Disorders • Osteoarthritis • Pain

First participants enrolled in Clinical Trial with Nociceptin/Orphanin peptide receptor (NOP) agonist (PRNewswire) - "Today, Grünenthal announced that the first participants have been enrolled in a randomised, placebo- and active-controlled clinical trial for its peripherally restricted Nociceptin/Orphanin FQ peptide receptor (NOP) agonist....The results of the trial are expected to be available in early 2022....In addition, Grünenthal intends to start a Phase IIa trial to evaluate the compound's efficacy in patients with painful diabetic peripheral neuropathy in 2022....In addition, Grünenthal intends to enrol the first patients with painful osteoarthritis of the knee in a Phase III clinical trial to investigate the efficacy, safety and tolerability of Resiniferatoxin by Q1 2022."

Clinical data • Enrollment status • New P2a trial • CNS Disorders • Diabetic Neuropathy • Neuralgia • Osteoarthritis • Peripheral Neuropathic Pain

Grünenthal acquires Mestex AG and its Phase-III-ready investigational medicine MTX-071 for the treatment of pain associated with osteoarthritis of the knee (PRNewswire) - "Today, Grünenthal has announced the acquisition of Mestex AG through the takeover of all of its shares and options. Mestex AG is a Swiss biotech company that has developed the innovative investigational medicine MTX-071 (resiniferatoxin) for the intra-articular treatment of pain associated with osteoarthritis of the knee. The investigational medicine is currently concluding Phase II of clinical development and is about to enter Phase III...Grünenthal is currently preparing two pivotal Phase III studies to investigate the efficacy, safety and tolerability of MTX-071 in patients with pain associated with osteoarthritis of the knee. The studies will start in 2021 and they are part of a global development programme aimed at meeting the requirements for approval in the EU, the US, Japan and China."

M&A • New P3 trial • CNS Disorders • Osteoarthritis • Pain