Solanezumab, or sola, binds the amyloid-βpeptides that aggregate and form plaques in the brain that are an early pathological feature of Alzheimer's disease. Sola binds the central epitope of monomeric amyloid-β, KLVFFAD, (PDB ID 4XXD) with picomolar affinity. This epitope is known as the nucleation site for Aβ oligomerization, and it is these oligomers of Aβ that are thought to be toxic to neurons.
The two Phase III trials were EXPEDITION 1 and EXPEDITION 2. EXPEDITION 1 didn't meet the predefined assessments. Lilly changed the predefined study goal in EXPEDITION 2, but EXPEDITION 2 didn't meet that goal either. Pooled data from EXPEDITION 1 and EXPEDITION 2 demonstrated a statistically significant slowing of cognitive decline in patients with mild AD but not in moderate AD, according to Lilly in 2012.
A Lilly-funded researcher said it was the "first evidence that targeting the amyloid cascade can slow the progression of disease.”
A BBC story reported that Lilly's data, presented at a conference but not yet published in a peer-reviewed journal, "suggests" solanezumab can cut the rate of progression of dementia by 34%, which means the amount of decline normally seen in 18 months would take 24 months. A confirmation trial, scheduled for reporting in 2016, is currently underway to determine if the effects are reproducible.
An ex-FDA official told the Financial Times that solanezumab “does not have a snowball’s chance in a very hot place” of getting conditional approval. To the FDA, missing the primary endpoint in a Phase III trial is “fatal.”
^Watt, Andrew D.; Crespi, Gabriela A. N.; Down, Russell A.; Ascher, David B.; Gunn, Adam; Perez, Keyla A.; McLean, Catriona A.; Villemagne, Victor L.; Parker, Michael W.; Barnham, Kevin J.; Miles, Luke A. (2014). "Do current therapeutic anti-Aβ antibodies for Alzheimer's disease engage the target?". Acta Neuropathologica127 (6): 803–10. doi:10.1007/s00401-014-1290-2. PMID24803227.