Raylumis (tanezumab) / Eli Lilly, Pfizer - LARVOL DELTA

Comparing Joint Safety Outcomes from Phase 2 RCTs of Two Different Neurotrophin Modulators: LEVI-04 (P75NTR-FC, NT-3 Inhibitor) and Fasinumab (Anti-NGF) (EULAR 2026) - "Previous analgesic therapies selectively targeting nerve growth factor (NGF) inhibition, such as fasinumab (FAS) and tanezumab provided analgesia but were dose-dependently associated with significant joint pathologies, including rapidly progressive OA (RPOA1, RPOA2), osteonecrosis (ON) and subchondral insufficiency fractures (SIFs). LEVI-04 demonstrated a safety and tolerability profile comparable to placebo, representing a de-risked therapeutic approach for OA pain. Longer term trials are in planning."

Clinical • P2 data • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • NGFR • NTF3

Analgesic, anti-inflammatory and joint protective effects of ACD137, a selective negative allosteric modulator of TrkA, in models of chemotherapy-induced peripheral neuropathy and osteoarthritis. (PubMed, Scand J Pain) - "The data demonstrates that ACD137 is a potent, selective and in vivo active negative allosteric modulator of TrkA exhibiting analgesic effects in models of neuropathic and nociceptive pain. The molecule possesses promising properties for further pre-clinical development."

Journal • Immunology • Inflammation • Neuralgia • Osteoarthritis • Pain • Peripheral Neuropathic Pain • Rheumatology • NGFR • NTRK2 • NTRK3

Efficacy and Safety of Anti-nerve Growth Factor Monoclonal Antibodies in Managing Chronic Musculoskeletal Pain: A Systematic Review with Network Meta-analysis. (PubMed, Drugs) - "Anti-NGF mAbs, particularly fasinumab and tanezumab, are associated with the greatest levels of pain relief and functional improvement over placebo within this analysis. However, these benefits are counterbalanced by significant risks of joint-related adverse events. Implementation of strict safety protocols is essential when considering these agents for further evaluation."

Journal • Retrospective data • Review • Back Pain • Immunology • Lumbar Back Pain • Musculoskeletal Diseases • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Off-target reactivity in clinical monoclonal antibodies. (PubMed, Structure) - "We further identified new off-target interactions of tanezumab and engineered its variable domains to eliminate off-target binding while preserving target affinity and developability. These findings highlight the prevalence of specific off-target reactivity in therapeutic antibodies and underscore the importance of evaluating specificity early in biologic drug development."

Journal

Comparison of tanezumab and non-steroidal anti-inflammatory drugs in efficacy and safety for chronic low back pain: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Front Neurol) - "The 5 mg dose, shows a comparable safety profile but no significant therapeutic advantages. While joint safety events significantly impacted development of tanezumab for OA, their rare occurrence in peripheral joints with pre-existing OA and absence in the lumbar spine within CLBP trials suggests its risk-benefit profile appears more acceptable in CLBP than in OA."

Journal • Retrospective data • Review • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

Biologic Innovation in Pain Management: Monoclonal Antibodies Targeting IL-6, TNF-α, TRPV1, and Neuroinflammatory Pathways (PAINWeek 2025) - "Similarly, anti-NGF monoclonal antibodies like tanezumab improved osteoarthritis symptoms in non-responders to conventional therapy but have been associated with joint-related adverse events, limiting use... Monoclonal antibodies targeting IL-6 and TNF-α demonstrated significant pain reduction and improved function in inflammatory and neuropathic conditions such as rheumatoid arthritis and sciatica. These therapies were generally well tolerated and had a more favorable safety profile than NSAIDs and opioids. Preclinical studies of anti-TRPV1 antibodies showed decreased nociceptor activation and thermal hyperalgesia, suggesting translational potential."

Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Musculoskeletal Pain • Neuralgia • Pain • Psychiatry • CX3CL1 • IL6 • TNFA • TRPV1

Incorporating Multiple Imputation Into Tanezumab Dose-Response Modeling of WOMAC Pain CFB Across Six Randomized Placebo-Controlled Phase 3 Trials. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "For a pre-defined statistical model, this is relatively straightforward, but for model development as typically conducted in Pharmacometrics, it is unclear how such an approach could be implemented. This case study describes how this was addressed at the time of a regulatory submission and considers alternative approaches which could be adopted in the future."

Journal • P3 data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Re: Re: Laboratory safety evaluation of bedinvetmab, a canine anti-nerve growth factor monoclonal antibody, in dogs. (PubMed, Vet J) - "Their questions appear to have stemmed from an anti-NGF mAb developed for the treatment of osteoarthritis in humans (tanezumab; FDA, 2021) which in 2021 failed to achieve marketing approval due to an unfavorable benefit: risk profile, primarily due to a syndrome called Rapidly Progressive Osteoarthritis (RPOA) which occurred more commonly in treatment groups when compared to controls...These findings have previously been determined to be incidental and not bedinvetmab-associated. To address the questions posed, it is important to briefly define RPOA and summarize the syndrome in humans, review why the bone/joint findings in bedinvetmab safety studies in dogs are not indicative of RPOA or an RPOA-like condition, provide an update on joint health after use of bedinvetmab since market approval (>3 years in some markets), and summarize why Zoetis, the manufacturer of Librela, has confidence in joint safety after use of bedinvetmab in dogs."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology

Effect size varies based on calculation method and may affect interpretation of treatment effect: an illustration using randomised clinical trials in osteoarthritis. (PubMed, Adv Rheumatol) - P3 | "Differences in ES affect interpretation of treatment effect. Therefore, we advocate clearly reporting individual elements of ES in addition to its overall calculation. This is particularly important when ES estimates are used to determine sample sizes for clinical trials, as larger ES will lead to smaller sample sizes and potentially underpowered studies."

Journal • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Phase 2 Randomized, Double-blind, Placebo-controlled Study of the Anti-nerve Growth Factor (NGF) Antibody Tanezumab in Subjects with Moderate to Severe Pain Due to Schwannomatosis (AAN 2024) - "Among schwannomatosis patients with moderate-to-severe pain, tanezumab reduced pain intensity; although these changes reflect clinically meaningful differences (2 points), they lacked statistical significance. Limited enrollment during the pandemic resulted in an underpowered study. A larger trial is needed to assess tanezumab's potential for treating SWN-related pain."

Clinical • P2 data • Brain Cancer • Immunology • Neuralgia • Osteoarthritis • Pain • Rheumatology • Solid Tumor • NGF

Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis (clinicaltrials.gov) - P2 | N=9 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Mar 2024 ➔ Sep 2024

Trial completion date • Brain Cancer • Pain • Solid Tumor

Characterization of adverse joint outcomes in patients with osteoarthritis treated with subcutaneous tanezumab. (PubMed, Osteoarthritis Cartilage) - P3 | "In placebo- and NSAID controlled studies of SC tanezumab for OA, adjudicated CJSE, RPOA, and TJR most commonly occurred in patients treated with tanezumab and with more severe radiographic or symptomatic OA. NCT02697773; NCT02709486; NCT02528188."

Adverse events • Journal • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology

Various Doses of Tanezumab in the Management of Chronic Low Back Pain (CLBP): A Pooled Analysis of 4,514 Patients. (PubMed, Cureus) - "However, tanezumab 5 mg showed significantly less reduction of LBPI compared to 10 mg at two, four, eight, and 12 weeks (MD ranging from 0.19 to 0.32). These findings suggest that tanezumab is an effective treatment for CLBP, with 5 mg and 10 mg doses providing clinically meaningful reductions in LBPI."

Journal • Retrospective data • Review • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

Phase 2 Randomized, Double-blind, Placebo-Controlled Study of the Anti-Nerve Growth Factor (NGF) Antibody Tanezumab in Subjects with Moderate to Severe Pain Due to Schwannomatosis (SNO 2023) - "Nine subjects were enrolled (median age 44 years, 7 females). At baseline, mean NRS-11 score was 7.6 (SD 2.1) and mean PROMIS-PI T-score was 63.2 (SD 6.6). During double-blind treatment, four participants were randomized to receive tanezumab (early group) and five were randomized to placebo (delayed group)."

Clinical • P2 data • Brain Cancer • Immunology • Osteoarthritis • Pain • Rheumatology • Solid Tumor • NGF

Prediction of relative change in free nerve growth factor (NGF) following subcutaneous administration of tanezumab, a novel monoclonal antibody to NGF. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P3 | "Free NGF concentration was predicted to return to baseline level at ~8 weeks (95% prediction interval: 5-16 weeks) after the last tanezumab dose. This model adequately described plasma tanezumab and serum total NGF concentrations following subcutaneous administration of tanezumab 2.5 or 5 mg Q8W, allowed prediction of relative change in systemic free NGF following subcutaneous (SC) administration of tanezumab."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology

Peripheral Nerve Safety of Nerve Growth Factor Inhibition by Tanezumab: Pooled Analyses of Phase III Clinical Studies in Over 5000 Patients with Osteoarthritis. (PubMed, Clin Drug Investig) - P3 | "Tanezumab IV or SC had an increased incidence of AEs of APS, such as paresthesia and hypoesthesia, and diagnoses of mononeuropathy compared with placebo. However, tanezumab was not associated with generalized peripheral neuropathy."

Journal • P3 data • Immunology • Osteoarthritis • Pain • Peripheral Neuropathic Pain • Rheumatology

A Randomized Placebo-Controlled Trial of the Anti-Nerve Growth Factor Antibody Tanezumab in Subjects With Cancer Pain Due to Bone Metastasis. (PubMed, Oncologist) - P3 | "Tanezumab 20 mg met the primary efficacy endpoint at week 8. Conclusions on longer-term efficacy are limited since the study was not designed to evaluate the durability of the effect beyond 8 weeks. Safety findings were consistent with adverse events expected in subjects with cancer pain due to bone metastasis and the known safety profile of tanezumab. Clinicaltrials.gov identifier: NCT02609828."

Clinical • Journal • Musculoskeletal Diseases • Musculoskeletal Pain • Neuralgia • Oncology • Pain • Solid Tumor

Role of imaging for eligibility and safety of a-NGF clinical trials. (PubMed, Ther Adv Musculoskelet Dis) - "In 2021, an FDA advisory committee voted against approving tanezumab (one of the a-NGF compounds being evaluated) and declared that the risk evaluation and mitigation strategy was not sufficient to mitigate potential safety risks...In OA efficacy trials image acquisition and evaluation aims at maximizing sensitivity in order to capture structural effects between treated and non-treated participants in longitudinal fashion. In contrast, the aim of imaging in a-NGF trials is to enable detection of structural tissue alterations that either increase the risk of a negative outcome (eligibility) or may result in termination of treatment (safety)."

Journal • Review • Immunology • Osteoarthritis • Pain • Rheumatology

Barriers to participation in a prospective clinical trial for schwannomatosis-related pain (AAN 2023) - P2 | "A clinical trial of tanezumab, an anti-nerve growth factor antibody, was initiated for SWN-related pain (NCT04163419)...Importantly, participants did not cite the double-blind design as a reason for non-participation. These results will inform design of future prospective clinical trials for SWN-related pain."

Clinical • Brain Cancer • Immunology • Oncology • Osteoarthritis • Pain • Rheumatology • Solid Tumor

The Current Role of Disease-modifying Osteoarthritis Drugs. (PubMed, Arch Bone Jt Surg) - "It was encountered that many publications have analyzed the impact of several DMOAD methods, including anti-cytokine therapy (tanezumab, AMG 108, adalimumab, etanercept, anakinra), enzyme inhibitors (M6495, doxycycline, cindunistat, PG-116800), growth factors (bone morphogenetic protein-7, sprifermin), gene therapy (micro ribonucleic acids, antisense oligonucleotides), peptides (calcitonin) and others (SM04690, senolitic, transient receptor potential vanilloid 4, neural EGFL-like 1, TPCA-1, tofacitinib, lorecivivint and quercitrin). In conclusion, even though DMOADs seem promising, their clinical effectiveness has not yet been demonstrated for managing OA. Until forthcoming studies can proved the medications' capacity to repair and regenerate tissues affected by OA, physicians should keep using treatments that only intend to alleviate pain."

Journal • Review • Gene Therapies • Immunology • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • NELL1

Examining the Relationships Among Treatment, Pain, and Physical Function in Patients with Osteoarthritis: A Mediation-Modeling Approach. (PubMed, Clin J Pain) - P3 | "At least 75% of the treatment effect of tanezumab on physical functioning can be explained by the improvements in pain. However, tanezumab had an additional effect on physical functioning (~25%), which was independent of improvements in pain. Such independent effects are of considerable interest and require further research to determine their mechanisms."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology

Predicting Treatment Responses in Patients with Osteoarthritis: Results from Two Phase 3 Tanezumab Randomized Clinical Trials. (PubMed, Clin Pharmacol Ther) - P3 | "These secondary-data analyses identified distinct and common patient-based variables to predict response to placebo or tanezumab. These findings will inform the design of future clinical trials helping to move forward clinical pharmacology and translational science."

Clinical • Journal • P3 data • Immunology • Osteoarthritis • Pain • Rheumatology

Clinical characteristics of immune checkpoint inhibitor-related type 1 diabetes mellitus (PubMed, Zhonghua Yi Xue Za Zhi) - "The drugs used in 10 patients were all programmed cell death receptor 1 (PD-1) inhibitors, including 5 cases of pembrolizumab, 3 cases of sintilimab, 1 case of tanezumab, and 1 case of toripalimab. All the 10 patients were successfully treated and depended on insulin therapy. Immune checkpoint inhibitors can cause type 1 diabetes, including fulminant type 1 diabetes, which mostly begins with DKA, requiring early identification and aggressive insulin therapy."

Checkpoint inhibition • Journal • Diabetes • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Immune Modulation • Inflammation • Lung Cancer • Metabolic Disorders • Nasopharyngeal Carcinoma • Oncology • Renal Cell Carcinoma • Solid Tumor • Type 1 Diabetes Mellitus

Different Dosage Regimens of Tanezumab for the Treatment of Chronic Low Back Pain: A Meta-analysis of Randomized Controlled Trials. (PubMed, Clin Neuropharmacol) - "Intravenous and subcutaneous tanezumab injections as treatment for improving CLBP have promising clinical application as its great improvement on all efficacy and its controllable safety issues. Furthermore, intravenous and subcutaneous tanezumab injections were proved to achieve excellent and long-term curative effect on CLBP through our subgroup analysis and comparison."

Journal • Retrospective data • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

Time to first and sustained improvement in WOMAC domains among patients with osteoarthritis receiving tanezumab. (PubMed, Osteoarthr Cartil Open) - P3 | "Time to improvement of 50% was more variable, with first and sustained events expected within 4-16 and 8-24 weeks, respectively. NCT02697773; NCT02709486; NCT02528188."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology