Solanezumab

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Solanezumab
Monoclonal antibody
Type Whole antibody
Source Humanized
Target Beta amyloid
Legal status
Legal status
  • Investigational
Identifiers
CAS Number 955085-14-0 N
ATC code none
ChemSpider none
UNII 5D6PWO0333 YesY
KEGG D10058 N
Chemical data
Formula C6396H9922N1712O1996S42
Molar mass 144.1 kg/mol
 NYesY (what is this?)  (verify)

Solanezumab (proposed INN) is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector[1] for patients with Alzheimer's disease.[2][3] The drug attracted extensive media coverage proclaiming it a breakthrough, and the drug is currently undergoing Phase III trials.[4]

Solanezumab, or sola, binds the amyloid-β peptides that aggregate and form plaques in the brain that are an early pathological feature of Alzheimer's disease.[5] Sola binds the central epitope of monomeric amyloid-β, KLVFFAD, (PDB ID 4XXD[6]) with picomolar affinity.[7] 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.[8][9] The drug currently has high expectations, however, amidst a market of failed Alzheimer's drugs by outside pharma companies.

References[edit]

  1. ^ International Nonproprietary Names for Pharmaceutical Substances (INN, prepublication copy), World Health Organization.
  2. ^ Clinical trial number NCT00749216 for "Solanezumab Safety Study in Japanese Patients With Alzheimer's Disease" at ClinicalTrials.gov
  3. ^ Clinical trial number NCT00905372 for "Effect of LY2062430 on the Progression of Alzheimer's Disease (EXPEDITION)" at ClinicalTrials.gov
  4. ^ McCartney M (2015). "Margaret McCartney: The "breakthrough" drug that's not been shown to help in Alzheimer's disease". BMJ. 351: h4064. doi:10.1136/bmj.h4064. PMID 26208710. 
  5. ^ Villemagne, Victor L; Burnham, Samantha; Bourgeat, Pierrick; Brown, Belinda; Ellis, Kathryn A; Salvado, Olivier; Szoeke, Cassandra; MacAulay, S Lance; Martins, Ralph; Maruff, Paul; Ames, David; Rowe, Christopher C; Masters, Colin L; Australian Imaging Biomarkers Lifestyle (AIBL) Research Group (2013). "Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: A prospective cohort study". The Lancet Neurology. 12 (4): 357–67. doi:10.1016/S1474-4422(13)70044-9. PMID 23477989. 
  6. ^ Crespi, Gabriela A. N.; Hermans, Stefan J.; Parker, Michael W.; Miles, Luke A. (2015). "Molecular basis for mid-region amyloid-β capture by leading Alzheimer's disease immunotherapies". Scientific Reports. 5: 9649. doi:10.1038/srep09649. PMID 25880481. 
  7. ^ 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 Neuropathologica. 127 (6): 803–10. doi:10.1007/s00401-014-1290-2. PMID 24803227. 
  8. ^ Christian Nordvist (9 Oct 2012). "Lilly's Solanezumab Slows Down Alzheimer's Progression". Medical News Today. 
  9. ^ Anusha Kambhampathy, Jenifer C. Smith-Parker. (4 Sep 2012). "Eli Lilly's solanezumab faces grim prospects of attaining conditional FDA approval in mild Alzheimer's". Financial Times.