fulranumab (AMG-403) / Amgen - LARVOL DELTA

Standardized efficacy and safety evaluation of fulranumab for osteoarthritis. (PubMed, Clin Rheumatol) - "Patients with osteoarthritis can have a considerable improvement in their WOMAC, short pain inventory, patient global assessment scores, clinical symptoms, and overall quality of life. One possible therapeutic approach for the condition might be to use fulranumab."

Journal • Review • Immunology • Osteoarthritis • Pain • Rheumatology

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

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

Monoclonal Antibody Therapy for the Treatment of Interstitial Cystitis. (PubMed, Biologics) - "The monoclonal antibodies included in the review were the anti-tumor necrosis factor-α (anti-TNF-α) agents adalimumab, which showed no difference compared to placebo, and certolizumab pegol, which showed statistically important differences in all outcome measures compared to placebo at the 18-week follow-up visit. 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."

Journal • Review • Immunology • Interstitial Cystitis • Oncology • Pain • NGF

Different Drugs for the Treatment of Painful Diabetic Peripheral Neuropathy: A Meta-Analysis. (PubMed, Front Neurol) - "Pregabalin, duloxetine, tapentadol, lacosamide, mirogabalin, and capsaicin were all more effective than placebo in alleviating the pain associated with diabetic peripheral neuropathy, while ABT-894 and gabapentin showed no significant effect. In addition, the efficacy of buprenorphine, tanezumab, fulranumab and others could not be concluded due to insufficient studies...For the results of our meta-analysis, long-term studies are still needed to verify their efficacy and safety in the future. Systematic Review Registration: PROSPERO, identifier: CRD42020197397."

Retrospective data • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain • Psychiatry

Fulranumab as Adjunctive Therapy for Cancer-Related Pain: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study. (PubMed, J Pain) - P2 | "REGISTRATION: ClinicalTrials.gov identifier: NCT00929188 PERSPECTIVE: Efficacy and safety of fulranumab as adjunctive pain therapy in terminally-ill cancer patients were assessed. Results suggest that anti-NGF agents may prove to be novel additions in helping to optimize pain relief in cancer patients who fail to respond adequately to opioids and other common co-analgesics."

Clinical • Journal • P2 data • Fatigue • Oncology • Pain

Safety and efficacy of fulranumab in osteoarthritis of the hip and knee: results from four early terminated phase III randomized studies. (PubMed, Curr Med Res Opin) - P3 | "Within the limited sample analyzed, fulranumab showed evidence of improvement of pain and function in patients with moderate-to-severe osteoarthritis who had failed prior therapy and were candidates for joint replacement surgery. Fulranumab as adjuvant or monotherapy was well tolerated with no new safety signals Fulranumab demonstrated evidence suggestive of efficacy in osteoarthritic pain of hip and knee Fulranumab demonstrated evidence suggestive of improvement of pain and physical function in osteoarthritis."

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

FDA panel says pain drug trials should continue (Reuters) - The advisers to the FDA voted 21-0 that the agency should lift its hold on clinical trials of the drugs, from the class of anti-nerve growth factors; Pfizer, Regeneron and Johnson & Johnson are now pitching to resume wider trials

FDA advisory committee review • Pain

Janssen R&D discontinues fulranumab phase III program with Amgen (Pharmalive) - "Janssen Research & Development...terminated its Phase III development program for fulranumab in osteoarthritis pain due to a 'strategic portfolio prioritization,' the company announced late Thursday....In March, Janssen Research & Development struck a deal with Genentech (RHHBY) to initiate two studies to determine the safety and tolerability of daratumumab (Darzalex) and atezolizumab for treatment of in multiple myeloma and in solid tumor."

Anticipated new trial • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology • Pain

Serious joint-related adverse events in randomized controlled trials of anti-nerve growth factor monoclonal antibodies. (PubMed) - "Indeed, the syndrome of rapid progression of OA associated with chondrolysis and bone destruction appears to be a safety signal that is associated with not only increasing doses of anti-NGF antibodies but also concomitant therapy with nonsteroidal anti-inflammatory drugs.` These results have implications for future clinical trials of anti-NGF agents in OA and other painful conditions."

Adverse events • Biosimilar • Growth Hormone • Immunology • Inflammation • Osteoarthritis • Pain

Emerging therapies in clinical development and new contributions for neuropathic pain. (PubMed, Rev Esp Anestesiol Reanim) - "New drugs that act on different therapeutic targets are currently in preclinical development or in their first phases of clinical development. In this review, focus will be directed specifically on new pharmacological treatments for neuropathic pain for which clinical data are already available, including older and known drugs with new data on their anti-neuropathic activity."

Clinical • Journal • Neuralgia • Pain

Development of a method that eliminates false-positive results due to nerve growth factor interference in the assessment of fulranumab immunogenicity (AAPS J) - "...only one strategy specifically removed NGF and produced true fulranumab-specific ADA results by using competitive inhibition with fulranumab and utilizing an alternative NGF binding antibody to eliminate NGF interference. Using this new method, we confirmed that the high apparent anti-fulranumab antibody incidence (>60%) in clinical study samples was in fact due to fulranumab-bound NGF released during the acid-dissociation step of the ADA testing method."

Preclinical • Pain

Fulranumab for treatment of diabetic peripheral neuropathic pain (Neurology) - P2, N=77; NCT00993018; Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.; "The primary endpoint, the mean reduction of average daily pain at week 12 compared with baseline, showed a positive dose-response relationship (p = 0.014, 1-sided); the pair-wise comparison between the 10-mg group and placebo was significant (unadjusted p = 0.040, 2-sided). An exploratory responder analysis revealed that a greater proportion of patients in the 10-mg group reported ≥30% reduction in the average DPNP intensity compared with placebo at week 12 (p = 0.006)."

P2 data • Pain

Analgesic efficacy of fulranumab in patients with painful diabetic peripheral neuropathy in a randomized, placebo-controlled, double-blind study (AAN 2013) - Presentation time: Thursday, March 21, 2013 2:15 PM; P2, N=77; NCT00993018; "Due to US FDA clinical hold, only 77 of planned 200 patients were enrolled...Change in 7-day average of daily pain intensity score from baseline to end of 12 week DB efficacy phase (primary endpoint) showed a positive dose response (p=0.014, one-sided). At DB efficacy endpoint, the pair-wise comparison between 10 mgQ4wk dose to placebo was significant (nominal p=0.04, two-sided)."

P2 data • Pain

JNJ: Pharmaceutical Business Review (Johnson and Johnson Ltd) - “Fulranumab Improves Pain and Function in Osteoarthritis”

P2 data • Pain

Anti-NGF therapy for cancer pain: More research needed (Medscape) - P2, N=100; NCT00929188; Sponsor: Janssen Research & Development, LLC; "Adding a novel anti–nerve growth factor product to opioids for terminally ill patients with inadequately controlled cancer pain did not significantly improve average cancer pain intensity in a phase 2 study, but secondary endpoints were encouraging....The primary efficacy outcome, the mean change in average cancer pain intensity score from baseline to end of DB, showed no significant difference between the two arms: -0.8 with fulranumab vs -0.7 for placebo (P = .592)."

P2 data • Pain

JNJ Pharmaceuticals: Business Review (Johnson and Johnson Ltd) - "Fulranumab Improves Pain and Function in Osteoarthritis and Diabetic Peripheral Neuropathy"

P2 data • Pain

JNJ: Pipeline Update (J&J) - Anticipated BLA submission for osteoarthritis pain in 2015-2019; Anticipated EU regulatory filing for osteoarthritis pain in 2015-2019

Anticipated BLA • Anticipated EU regulatory • Pain

Efficacy, safety, and tolerability of fulranumab, an anti-nerve growth factor antibody, in treatment of patients with moderate to severe osteoarthritis pain (Pain) - P2, N=466; PMID: 23748114; NCT00973141; Sponsor: Janssen Research & Development; "Primary efficacy results showed that fulranumab significantly reduced the average pain intensity score...from baseline to week 12 versus placebo in the 3mgQ4wk, 6mgQ8wk, and 10mgQ8wk groups...Fulranumab treatment resulted in statistically significant efficacy in pain measures and physical function versus placebo, and was generally well-tolerated."

P2 data • Pain

Double-blind, randomized study to evaluate efficacy, and safety of fulranumab in patients with moderate to severe, chronic knee pain from osteoarthritis: Interim analysis results (APS 2013) - P2, N=196; NCT01094262; Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C; "Both fulranumab groups showed significant improvement in pain relief in the responder analysis versus oxycodone CR (nominal p-values: 0.008 [3mgQ4wk]; 0.012 [9mgQ4wk]); neither fulranumab group separated statistically from placebo group (nominal p-values: 3mgQ4wk = 0.74, 9mgQ4wk = 0.84), which had a high response rate. Mean changes in average pain intensity scores from baseline to week 12 were consistent with the primary endpoint results: -3.0 (placebo and fulranumab 9mgQ4), -2.9 (fulranumab 3mgQ4), and -1.6 (oxycodone CR)."

P2 data • Pain

JNJ: Pharmaceutical Business Review (J&J) - Anticipated regulatory filing for osteoarthritis pain in 2019

Anticipated regulatory • Pain

Study of Efficacy, Safety of Fulranumab Adjunctive Use in OA of Hip or Knee, PAI3001 (clinicaltrials.gov) - P3; N=450; Recruiting; Sponsor: Janssen Research & Development, LLC; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Immunology • Inflammation • Osteoarthritis • Pain

Study of Efficacy, Safety of Fulranumab Adjunctive Use in OA of Hip or Knee, PAI3001 (clinicaltrials.gov) - P3; N=450; Not yet recruiting; Sponsor: Janssen Research & Development, LLC

New P3 trial • Biosimilar • Immunology • Inflammation • Osteoarthritis • Pain

Evaluation of the Toxicity and Neurological Effects of Fulranumab in Adult Cynomolgus Monkeys. (PubMed, Int J Toxicol) - "Fulranumab did not cause any neuronal death, necrosis, apoptosis, or any apparent decrease in function of sympathetic neurons/ganglia at any time point examined. A no observed effect level (NOEL) was established at 0.25 mg/kg fulranumab SC every 4 weeks for 28 weeks."

Clinical • Journal