title: Fasinumab (REGN475), an antinerve growth factor monoclonal antibody, for the treatment of acute sciatic pain: results of a proof-of-concept study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of subcutaneously administered fasinumab (REGN475), a nerve growth factor-neutralizing antibody, in patients with acute sciatic pain receiving standard of care therapy.
  
  
  METHODS
  This was a double-blind, parallel-group, proof-of-concept study. Patients with unilateral, moderate-to-severe sciatic pain of 2-16 weeks' duration were randomized to a subcutaneous dose of placebo (n=51), fasinumab 0.1 mg/kg (n=53), or 0.3 mg/kg (n=53); follow-up was 12 weeks. Pain was assessed in a daily diary using a numerical rating scale (NRS) (0= no pain, 10= worst pain) for average and worst leg and back pain. The primary efficacy end point was the area under the curve of NRS scores for average leg pain from baseline to week 4. Key secondary end points included changes in average and worst leg and back pain from baseline to the end of week 4 and to each weekly study visit. Patient functioning (Oswestry Disability Index) and concomitant analgesic use were also assessed. Safety and tolerability were evaluated by treatment-emergent adverse events (TEAEs).
  
  
  RESULTS
  Demographic and clinical characteristics were similar among the treatment groups; 141 (88.7%) patients completed the study. For the primary end point, mean ± standard deviation area under the curve values from baseline to week 4 were not significantly different between placebo (96.8±6.0) and fasinumab 0.1 mg/kg (112.7±58.3; P=0.0610) or fasinumab 0.3 mg/kg (112.4±55.8; P=0.0923). All secondary efficacy end points of changes in pain and function demonstrated responses that were similar between placebo and fasinumab groups. Incidence of TEAEs was 45.1%, 50.9%, and 64.8% in the placebo, fasinumab 0.1mg/kg, and fasinumab 0.3 mg/kg groups, respectively. The most commonly reported TEAEs included paresthesia, arthralgia, pain in extremity, and headache.
  
  
  CONCLUSIONS
  Administration of fasinumab provided no significant clinical benefit compared with placebo for the pain or functional limitations associated with acute sciatica. Fasinumab was generally well tolerated and incidence of TEAEs appeared to be dose related.
authors.affiliation: Pharmacovigilance Operations and Risk Management, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tiseo
authors.affiliation: Biostatitics, Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA.
authors.forename: Haobo
authors.initials: H
authors.lastname: Ren
authors.affiliation: Translational Medicine and Predictive Medicine, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Mellis
keywords: fasinumab; lumbar radiculopathy; monoclonal antibody; nerve growth factor; sciatica