- |||||||||| Raylumis (tanezumab) / Eli Lilly, Pfizer
Journal: Re: Re: Laboratory safety evaluation of bedinvetmab, a canine anti-nerve growth factor monoclonal antibody, in dogs. (Pubmed Central) - Aug 15, 2024 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.
- |||||||||| Raylumis (tanezumab) / Eli Lilly, Pfizer
Trial completion date: Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis (clinicaltrials.gov) - Mar 12, 2024 P2, N=9, Active, not recruiting, 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. Trial completion date: Mar 2024 --> Sep 2024
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Retrospective data, Review, Journal: Various Doses of Tanezumab in the Management of Chronic Low Back Pain (CLBP): A Pooled Analysis of 4,514 Patients. (Pubmed Central) - Nov 13, 2023 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.
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Review, Journal: Role of imaging for eligibility and safety of a-NGF clinical trials. (Pubmed Central) - Jun 7, 2023 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).
- |||||||||| Raylumis (tanezumab) / Eli Lilly, Pfizer
Barriers to participation in a prospective clinical trial for schwannomatosis-related pain (Both in-person and online) - Mar 12, 2023 - Abstract #AAN2023AAN_2780; 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.
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P3 data, Retrospective data, Journal: Efficacy and safety of tanezumab, NSAIDs, and placebo in patients with moderate to severe hip or knee osteoarthritis and a history of depression, anxiety, or insomnia: post-hoc analysis of phase 3 trials. (Pubmed Central) - Nov 22, 2022 P3 Patients with OA and a history of depression, anxiety, or insomnia did not appear to experience reduced efficacy outcomes or an altered safety profile in response to tanezumab or NSAID treatment as compared with those without. NCT02697773; NCT02709486; NCT02528188.
- |||||||||| Raylumis (tanezumab) / Eli Lilly, Pfizer
Journal: A Two-Step, Trajectory-Focused, Analytics Approach to Attempt Prediction of Analgesic Response in Patients with Moderate-to-Severe Osteoarthritis. (Pubmed Central) - Oct 28, 2022 P3 Analyzing initial 8-week analgesic responses using a two-step, trajectory-based approach can predict future response in patients with moderate-to-severe osteoarthritis treated with NSAIDs or 2.5 mg tanezumab. These findings demonstrate that prediction of treatment response based on a single dose of a novel therapeutic is possible and that predicting future outcomes based on initial response offers a way to potentially advance the approach to clinical management of patients with osteoarthritis.
- |||||||||| Raylumis (tanezumab) / Eli Lilly, Pfizer
Enrollment closed, Enrollment change, Trial primary completion date: Phase 2 Study of Tanezumab in Subjects With Moderate to Severe Pain Due to Schwannomatosis (clinicaltrials.gov) - Oct 18, 2022 P2, N=9, Active, not recruiting, It aims to establish a model for future pain studies in SWN and other rare diseases. Recruiting --> Active, not recruiting | N=46 --> 9 | Trial primary completion date: Jun 2023 --> Sep 2022
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Preclinical, Journal: Analgesic effects of nerve growth factor-directed monoclonal antibody on diabetic neuralgia in an animal model. (Pubmed Central) - Jul 8, 2022 Tanezumab, a monoclonal antibody that blocks nerve growth factor (NGF) signaling, has been shown to be effective in relieving the clinical symptoms of osteoarthritis pain, chronic low back pain, cancer pain induced by bone metastasis, and diabetic neuralgia...In a mouse diabetic neuralgia model, huAb45 effectively relieved neuropathic pain. This study may serve as a necessary foundation for future studies of the use of huAb45 to potentially treat diabetic neuralgia.
- |||||||||| Review, Journal: Monoclonal Antibody Therapy for the Treatment of Interstitial Cystitis. (Pubmed Central) - May 29, 2022
Anti-nerve growth factor (anti-NGF) agents were also reviewed, including tanezumab, which showed both positive and negative efficacy results compared to placebo, and fulranumab, the study of which was discontinued owing to adverse events. In summary, monoclonal antibody therapy remains to be further researched in order for it to be proposed as a promising future treatment option for PBS/IC.
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Retrospective data, Review, Journal: Efficacy and Safety of Anti-Nerve Growth Factor Antibody Therapy for Hip and Knee Osteoarthritis: A Meta-analysis. (Pubmed Central) - May 3, 2022 Sensitivity analysis was conducted to evaluate the effectiveness of tanezumab and the effectiveness of anti-NGF antibodies compared to active comparator drugs...Anti-NGF antibody treatment significantly relieved pain and improved function in patients with hip and knee OA. However, no conclusion could be drawn regarding the optimal treatment plan for anti-NGF antibodies when all 3 variables (dose, administration mode, and treatment duration) were combined in the analyses.
- |||||||||| lorecivivint (SM04690) / Biosplice Therap, Samil Pharma, Raylumis (tanezumab) / Eli Lilly, Pfizer
Journal: Osteoarthritis: what's new? (Pubmed Central) - Apr 30, 2022 Unfortunately, the results of the phase 2 study on the Wnt inhibitor lorecivivint are barely encouraging. However, the results of the according phase 3 study are eagerly awaited.
- |||||||||| Raylumis (tanezumab) / Eli Lilly, Pfizer
Journal: Tanezumab for the treatment of osteoarthritis pain. (Pubmed Central) - Apr 19, 2022 In 2017, tanezumab was granted fast track designation in the U.S. for the treatment of chronic pain in patients with OA, as well as for the treatment of chronic low-back pain. This review discusses the mechanism of action, preclinical data and phase I, II and III studies of efficacy and safety of tanezumab in patients with OA.
- |||||||||| Raylumis (tanezumab) / Eli Lilly, Pfizer
Journal: Neurological safety of subcutaneous tanezumab versus NSAID in patients with osteoarthritis. (Pubmed Central) - Apr 14, 2022 P3 Tanezumab had an increased incidence of AEs of APS versus NSAID; these were typically mild/moderate in severity, resolved during the study, and rarely resulted in discontinuation. Tanezumab was not associated with peripheral neuropathy and did not adversely affect the sympathetic nervous system.
- |||||||||| Review, Journal: Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets. (Pubmed Central) - Mar 18, 2022
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 histone methyltransferase inhibitor used in the management of T-cell lymphoma, or cercosporamide a MNK 1/2 inhibitor used in treatment of rheumatoid arthritis; (vi) combination therapy using drugs that are selective for different channel types or regulatory processes; (vii) directing preclinical validation work toward the use of human or human-derived tissue samples; and (viii) application of molecular biological approaches such as clustered regularly interspaced short palindromic repeats (CRISPR) technology.
- |||||||||| Raylumis (tanezumab) / Eli Lilly, Pfizer
Journal: Preparation and characterization of a high-affinity monoclonal antibody against nerve growth factor. (Pubmed Central) - Feb 8, 2022 Moreover, the specific reactivity of 58F10G10H was demonstrated by TF-1 cell proliferation activity experiments, competitive binding Enzyme-linked immunosorbent assay (ELISA) and the arthritis animal models in mice, respectively. In conclusion, in this study, a method for the preparation of high-yield NGF-HFC and NGF-His proteins was designed, and a high-affinity monoclonal antibody against NGF with potential for basic research and clinical application was prepared.
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