Chronic postsurgical pain — Capsaicin 8% skin patch

GSK-3 beta inhibition would reduce tau hyperphosphorylation and slow decline in mild-to-moderate Alzheimer's.

CSF p-tau181 dropped by 28% but ADAS-Cog showed no difference from placebo; the high-dose arm was halted for safety.

Why it matched: similar wording · failed the same way: Target engaged, outcome unchanged

Calmangafodipir, which reduced patient-reported chemotherapy-induced peripheral neuropathy in a randomised phase 2 trial, would prevent moderate-to-severe neuropathy in patients receiving oxaliplatin in the adjuvant and metastatic settings.

Both POLAR trials (n = 301 and 291) stopped early after unexpected hypersensitivity reactions. In the pooled primary analysis, 54.3% of calmangafodipir patients had moderate-to-severe neuropathy at month 9 versus 40.3% on placebo (relative risk 1.37, 95% CI 1.01–1.86, P = .045), and serious hypersensitivity reactions were more frequent (3.6% vs 0.8%).

Why it matched: failed the same way: Target engaged, outcome unchanged