Phase 2 Randomized, Double-blind, Placebo-controlled Study of the Anti-nerve Growth Factor (NGF) Antibody Tanezumab in Subjects with Moderate to Severe Pain Due to Schwannomatosis
Danielle Silverman1, Jennifer Da1, Vanessa Merker1, Ina Ly1, Alona Muzikansky1, Michael Parsons1, Pamela Wolters2, Lei Xu 1, Mark Brown3, Mehrdad Haghpassand 3, Justin Jordan1, Scott Plotkin1
1Massachusetts General Hospital, 2National Cancer Institute, 3Pfizer Inc.
Objective:
To assess the analgesic efficacy of subcutaneous tanezumab 10 mg in subjects with schwannomatosis (SWN)-related pain, administered alongside any pre-existing non-NSAID therapy. 
Background:

Schwannomatosis is a rare neurogenetic condition characterized by multiple schwannomas and severe chronic pain. Elevated nerve growth factor (NGF) levels identified in painful schwannomas prompted our study on tanezumab, an anti-NGF antibody, as a treatment for SWN-related pain.

Design/Methods:

We enrolled subjects (≥18 years) with moderate-to-severe SWN-related pain intensity [Numerical Rating Scale (NRS-11) score ≥5, range: 0-10 (no pain-worst pain)] despite use of neuropathic pain medications, NSAIDS, and opioids; able to discontinue NSAIDS; and without osteoarthritis.  The study included a double-blind period with patients randomized to tanezumab 10 mg SQ or placebo (days 1-56), followed by unblinded tanezumab 10 mg SQ treatment (days 57-112) for all patients, and safety follow-up (days 113-281) without treatment. We measured weekly changes in pain intensity from Baseline-Day 57, Day 57-Day 113, and Day 113-Day 169 and performed a one-tailed t-test (p<0.05) to evaluate tanezumab's efficacy.

Results:

9 subjects (median age: 44, range: 33-65, 7 females) were enrolled. The mean baseline NRS-11 score was 7.6 (SD 2.1).  During the double-blind period, 4 patients received tanezumab and 5 received placebo.  The mean change in NRS-11 score was -2.5 (SD 4.5) in the tanezumab/tanezumab group and -0.4 (SD 2.1) in the placebo/tanezumab group.  During unblinded treatment, the mean change in NRS-11 scores were 0 (SD 0) for the tanezumab/tanezumab group and -1.4 (SD 1.9) for the placebo/tanezumab group. During safety follow-up, the mean change in NRS-11 score was 0.8 (SD 1.6).

Conclusions:
Among schwannomatosis patients with moderate-to-severe pain, tanezumab reduced pain intensity; although these changes reflect clinically meaningful differences (2 points), they lacked statistical significance.  Limited enrollment during the pandemic resulted in an underpowered study.  A larger trial is needed to assess tanezumab’s potential for treating SWN-related pain. 
10.1212/WNL.0000000000205317