Results from a small study indicate patients with difficult-to-treat diabetic peripheral neuropathy (DPN) may benefit from therapy with tanezumab, a humanized monoclonal antibody against nerve growth factor.
Patients with difficult-to-treat diabetic peripheral neuropathy (DPN) may benefit from therapy with tanezumab, a humanized monoclonal antibody against nerve growth factor that is administered subcutaneously and has already shown efficacy in patients with chronic pain due to osteoarthritis and chronic low back pain.
According to results from a small, short-term study presented at the American Pain Society’s 32nd Annual Scientific Meeting, held May 8-13, 2013, in New Orleans, LA, patients with DPN who received one 20 mg dose of tanezumab reported significant improvements in pain scores compared with patients who received placebo.
For the study, 73 patients with type 1 or type 2 diabetes and a diagnosis of “painful, diabetic, distal, symmetrical, sensorimotor polyneuropathy evidenced by bilateral pain in the lower extremities due to DPN” were randomized to receive either tanezumab 20 mg subcutaneous injection (n=38) or placebo (n=35). All patients had experienced painful DPN for at least three months or more which had proven refractory to other treatment. Patients were not permitted treatment with concurrent opioids, anxiolytics, antiepileptics, antidepressants, or biologics, but were permitted to use prescription and/or OTC NSAIDs.
Mean age of study participants was 59.6 years for the placebo group and 61.6 years for the treatment group. Participants in both groups had experienced painful DPN symptoms for an average of 4.6 months, with an average DPN pain intensity of 6.9 for the placebo group and 6.6 for the treatment group, as measured by an 11-point numerical rating scale (NRS).
Researchers measured change from baseline to week 8 in average DPN score (the study was originally intended to be a 24-week study in which patients received two doses of tanezumab, but the study was prematurely halted by the FDA due to joint-related safety issues in other studies). They also assesses change from baseline to week 8 in Patients’ Global Assessment (PGA) of DPN, and percentage of patients with reduction in average DPN pain score equal to or greater than 30%, 50%, 70%, and 90%.
The authors documented adverse events, performed standardized physical and neurological exams on all participants, performed quantitative sensory testing (QST) to assess and quantify the sensory function of small and large nerve fibers in patients’ lower extremities, and measured nerve fiber density to evaluate whether treatment with tanezumab is associated structural changes in small sensory nerve fibers.
Analysis of study data indicated that “a larger mean reduction (improvement) in average DPN pain score from baseline to week 8 occurred in the tanezumab 20 mg treatment group (-2.7[observed], -2.2[LOCF]) compared with the placebo treatment group (-1.1[observed], -1.0[LOCF]).”
The percentage of patients with reduction in average DPN pain score equal to or greater than 30%, 50%, and 70% at week 8 were “significantly larger for the tanezumab 20 mg treatment group compared with placebo.” There was no significant difference between the two groups for percentage of patients with reduction in average DPN pain score equal to or greater than 90%. Also, more patients in the tanezumab treatment group showed an improvement of at least two grades in PGA of DPN at week 8 compared with placebo, though this did not reach statistical significance.
The frequency and types of adverse events reported by both groups were similar to that seen in other studies of patients with DPN, with arthralgia, back pain, and pain in the extremities the most frequently reported events. Two patients in the tanezumab treatment group experienced new or worsened peripheral neuropathy based on neurological evaluation, compared with no patients in the placebo group.
The authors reported no effect on patients’ QST thresholds, and a small decline in intraepidemral nerve fiber density in the tanezumab group.
Overall, the results of this small, short-term study show that subcutaneous tanezumab 20 mg is well tolerated and produces significant improvements in average DPN pain scores compared with placebo. Candace Bramson, MD, Pfizer Global Research and Development said the results from this study were encouraging and sugested that tanezumab has real promise as an effective treatment for DPN, with affects up to half of all patients with diabetes and is often difficult to treat.