fasinumab (REGN475) / Teva, Mitsubishi Tanabe, Regeneron - LARVOL DELTA

The Effects of Fasinumab on Peripheral Nerve Function and Ganglion Anatomy: Results From a Randomized, Double-Blind, Placebo-Controlled Study in Patients With Pain Due to Osteoarthritis of the Knee or Hip, and a Series of Nonclinical Studies. (PubMed, Curr Ther Res Clin Exp) - P2/3 | "In the nonclinical studies, no significant changes could be detected in adult rat ganglion anatomical parameters or hemodynamic parameters at a variety of fasinumab doses. Results from these studies demonstrated that fasinumab did not affect the tested nervous system parameters in adult humans or rats.Trial registration number: NCT02447276; https://clinicaltrials.gov/study/NCT02447276."

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

Efficacy of Fasinumab, An Anti-Nerve Growth Factor Monoclonal Antibody, in Managing Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis (ACR Convergence 2025) - "This meta-analysis shows that Fasinumab has promising results in managing chronic musculoskeletal pain and suggests it may be superior to placebo or conventional analgesics. Further studies involving more intervention arms are needed to come up with a more definitive answer."

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

Efficacy and safety of fasinumab in the treatment of osteoarthritis. (PubMed, Clin Exp Rheumatol) - "Fasinumab is a monoclonal antibody medication used to treat osteoarthritis and lessen pain. Fasinumab enhanced scores on the WOMAC function, WOMAC pain subscale, and numerical rating scale. Naturally, one cannot overlook the restrictions or difficulties brought on by limited sample sizes and demographic variety. Future research should promote the inclusion of bigger populations and larger sample sizes in order to develop an osteoarthritis treatment that is both affordable and effective."

Journal • Review • Immunology • Osteoarthritis • Pain • Rheumatology

Efficacy and safety of fasinumab in an NSAID-controlled study in patients with pain due to osteoarthritis of the knee or hip. (PubMed, BMC Musculoskelet Disord) - P3 | "Fasinumab significantly improved WOMAC pain and physical function scores versus placebo in < 24 weeks in difficult-to-treat patients with pain due to OA of the knee/hip. Adjudicated arthropathies were more frequent with fasinumab; there were no differences in the proportions of patients with joint replacements."

Clinical • Journal • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology

Certain Dosages of Fasinumab Provides Superior Benefits over Placebo in Mitigating Osteoarthritis Symptoms Albeit at Increased Health Detriments: A Systematic Review and Meta-Analysis (ACR Convergence 2024) - "Specific Fasinumab dosages showed greater efficacy in alleviating pain and improving function and PGA scores compared to placebo. However, Fasinumab use may be associated with increased health detriments, such as increased risk of adjudicated arthropathy and all-cause joint replacement."

Retrospective data • Review • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

A phase III study to evaluate the long-term safety and efficacy of fasinumab in patients with pain due to osteoarthritis of the knee or hip. (PubMed, Osteoarthr Cartil Open) - "AAs and JRs showed a dose relationship to fasinumab and were associated with baseline OA status. Fasinumab achieved statistically significant improvements in WOMAC pain and physical function scores compared with placebo."

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

Prevalence of preexisting articular bone pathology in patients with osteoarthritis screened for fasinumab clinical trials identified by X-ray or magnetic resonance imaging. (PubMed, Osteoarthritis Cartilage) - P3 | "Approximately one in 20 participants with OA who met the clinical screening criteria for fasinumab phase 3 trials were later excluded due to preexisting severe articular bone pathology findings by X-ray or MRI."

Journal • MRI • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Osteoporosis • Pain • Rheumatology

Population Pharmacokinetics of Fasinumab in Healthy Volunteers and Patients With Pain Due to Osteoarthritis of the Knee or Hip. (PubMed, Clin Pharmacol Drug Dev) - "Body weight had the largest predicted impact on fasinumab steady-state exposures, participants at the 5th and 95th percentiles had a 43%-45% higher/22%-23% lower exposure versus reference, respectively. Other covariates had small but clinically irrelevant impacts."

Journal • PK/PD data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Clinical efficacy and safety of monoclonal antibody against Nerve Growth Factor and Fibroblast Growth Factor-18 therapy of osteoarthritis (EULAR 2022) - "Currently osteoarthritis treatment includes acetaminophen, NSAIDs and/or opioids, intra-articular corticosteroid injections...Among 23 studies, 16 used anti-NGF monoclonal antibodies (Tanezumab, Fasinumab, Fulranumab), and 7 used recombinant human FGF-18 (Sprifermin)... In recent years significant progress has been achieved in search for pathogenetic therapy of OA. Based on the results of current research findings, NGF inhibitors relieved pain and enhance joint function and may be considered as the most effective for functional improvement. FGF-18 decrease the cartilage loss and may improve cartilage thickness."

Clinical • Back Pain • Gene Therapies • Immunology • Infectious Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Osteoarthritis • Otorhinolaryngology • Pain • Peripheral Neuropathic Pain • Respiratory Diseases • Rheumatology • Sinusitis • NGF

Mitsubishi Tanabe Pharma: Operating loss of 15.7 billion yen is expected to increase in FY2010, but sales are expected to increase in FY2010. [Google translation] (Mix Online) - "In addition, we reviewed the business plan for MT-5547 (anti-NGF antibody facinumab), which was introduced by Regeneron of the United States and is in the phase 2/3 study stage in Japan for osteoarthritis, in response to changes in the business environment. As a result, an impairment loss on intangible assets of 15.8 billion yen was recorded. The operating loss was 15.7 billion yen..."

Commercial • CNS Disorders • Osteoarthritis • Pain

Regeneron Pharmaceuticals : Annual Report (Form 10-K) (Market Screener) - "As of December 31, 2021, we had received an aggregate $120.0 million of development milestones from Teva, and we are entitled to receive up to an aggregate of $340.0 million in additional development milestones and up to an aggregate of $1.890 billion in contingent payments upon achievement of specified annual net sales amounts. We are responsible for the manufacture and supply of fasinumab globally."

Commercial • CNS Disorders • Immunology • Osteoarthritis • Pain

Nerve Growth Factor (NGF) Inhibitors and Related Agents for Chronic Musculoskeletal Pain: A Comprehensive Review. (PubMed, BioDrugs) - "Several phase 2/3 studies have been accomplished for these drugs, such as tanezumab, fasinumab, and tyrosine receptor kinase A (TrkA) inhibitors. In this narrative review, we briefly overview the disease burden of musculoskeletal pain, the role of NGF signaling and its receptors in the genesis of pain, and the mechanisms of action of inhibitors of NGF signaling and downstream pathways, and then discuss the efficacy and safety of each investigational drug in OA and LBP. Finally, we briefly review two serious adverse effects of NGF inhibitors, namely rapidly progressive OA and sympathetic system effects, and conclude with possible barriers and potential research directions to overcome these."

Journal • Review • Back Pain • Gastrointestinal Disorder • Immunology • Lumbar Back Pain • Musculoskeletal Diseases • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • NGF

Efficacy and Safety of MT-5547 in Patients With Osteoarthritis Accompanied by Moderate to Severe Pain (clinicaltrials.gov) - P2/3; N=626; Completed; Sponsor: Mitsubishi Tanabe Pharma Corporation; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

FACT OA1: A Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Naproxen for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip (clinicaltrials.gov) - P3; N=3307; Completed; Sponsor: Regeneron Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

FACT LTS & OA: Long-Term Safety and Efficacy Study of Fasinumab in Patients With Pain Due to Osteoarthritis (OA) of the Knee or Hip (clinicaltrials.gov) - P3; N=5331; Completed; Sponsor: Regeneron Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

FACT CLBP 1: Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate-to-Severe Chronic Low Back Pain and Osteoarthritis of the Hip or Knee (clinicaltrials.gov) - P3; N=63; Terminated; Sponsor: Regeneron Pharmaceuticals; Completed ➔ Terminated; Due to implementation of an urgent safety measure, enrollment and dosing in R475-PN-1612 was stopped; enrolled participants entered the 20-week safety follow-up

Clinical • Trial termination • Back Pain • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Antibodies to watch in 2021. (PubMed, MAbs) - "Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan...Based on the information publicly available as of November 2020, 44 antibody therapeutics are in late-stage clinical studies for non-cancer indications, including 6 for COVID-19, and marketing applications for at least 6 (leronlimab, tezepelumab, faricimab,..."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

FACT DEVICE: To Assess the Patients' Ability to Self-Administer Fasinumab (clinicaltrials.gov) - P1; N=100; Completed; Sponsor: Regeneron Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

Regeneron Reports Fourth Quarter and Full Year 2020 Financial and Operating Results (PRNewswire) - "Fourth quarter 2020 Dupixent® global net sales, which are recorded by Sanofi, increased 56% to $1.17 billion versus fourth quarter 2019 and full year 2020 Dupixent global net sales increased 75% versus 2019....Fasinumab (NGF Antibody): Report additional longer-term safety results from Phase 3 studies in osteoarthritis pain of the knee or hip. Continue discussions with regulatory authorities and determine next steps for the program."

P3 data • Sales • Asthma • Atopic Dermatitis • CNS Disorders • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Pruritus

Study to Evaluate the Effects of Fasinumab on Peripheral Nerve Function in Patients With Pain Due to Osteoarthritis of the Hip or Knee (clinicaltrials.gov) - P2; N=180; Completed; Sponsor: Regeneron Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

Fasinumab effective for chronic low back pain. (PubMed, Nat Rev Rheumatol) - No abstract available

Journal • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain

FACT OA2: Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip (clinicaltrials.gov) - P3; N=1650; Completed; Sponsor: Regeneron Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

Study to Evaluate Arthroplasty Specimens for Osteoarthritis of the Knee and Hip (clinicaltrials.gov) - P2; N=23; Terminated; Sponsor: Regeneron Pharmaceuticals; N=50 ➔ 23; Trial completion date: Jun 2021 ➔ Aug 2020; Enrolling by invitation ➔ Terminated; Trial primary completion date: Jun 2021 ➔ Aug 2020; Lack of enrollment

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

Efficacy and safety of fasinumab in patients with chronic low back pain: a phase II/III randomised clinical trial. (PubMed, Ann Rheum Dis) - "Fasinumab highest doses, but not lower dose, improved both CLBP pain and function. Most joint AEs occurred in pOA patients, consistent with earlier findings in symptomatic OA. Further study is needed of patients with CLBP with and without pOA to determine optimal benefit-risk."

Clinical • Journal • P2/3 data • Back Pain • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Nerve Growth Factor Inhibitor Study Highlights Promise as an OA Pain Treatment (The Rheumatologist) - "'We've recognized that there seems to be some very significant efficacy with nerve growth factor inhibitors that has been limited by the toxicity profile,' says Dr. Kivitz....'Because of such a dire need for help in our patients with OA pain, the limitations we have with our current interventions, I think there is a great need for treatments with new modes of action,' he says. 'I think nerve growth factor inhibitors could fill that role, as long as we carefully balance safety and efficacy.'"

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