Solanezumab, Eli Lilly’s anti-beta-amyloid monoclonal antibody for Alzheimer’s disease

1. immunoglobulin G1-kappa, anti-[Homo sapiens amyloid-beta (Abeta)

peptide soluble monomer], humanized monoclonal antibody;
gamma1 heavy chain [humanized VH (Homo sapiens IGHV3-23*04
(87.60%) -(IGHD)-IGHJ4*01) [8.8.5] (1-112) -Homo sapiens
IGHG1*01, CH3 K130>del (113-441)], (215-219′)-disulfide with
kappa light chain (1’-219’) [humanized V-KAPPA (Homo sapiens
IGKV2-30*01 (90.00%) -IGKJ1*01) [11.3.9] (1′-112′) -Homo sapiens
IGKC*01 (113′-219′)]; (221-221″:224-224″)-bisdisulfide dimer
neuroprotective agent
C6396H9922N1712O1996S42 955085-14-0

Heavy chain / Chaîne lourde / Cadena pesada
EVQLVESGGG LVQPGGSLRL SCAASGFTFS RYSMSWVRQA PGKGLELVAQ 50
INSVGNSTYY PDTVKGRFTI SRDNAKNTLY LQMNSLRAED TAVYYCASGD 100
YWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT 150
VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK 200
PSNTKVDKKV EPKSCDKTHT CPPCPAPELL GGPSVFLFPP KPKDTLMISR 250
TPEVTCVVVD VSHEDPEVKF NWYVDGVEVH NAKTKPREEQ YNSTYRVVSV 300
LTVLHQDWLN GKEYKCKVSN KALPAPIEKT ISKAKGQPRE PQVYTLPPSR 350
DELTKNQVSL TCLVKGFYPS DIAVEWESNG QPENNYKTTP PVLDSDGSFF 400
LYSKLTVDKS RWQQGNVFSC SVMHEALHNH YTQKSLSLSP G 441
Light chain / Chaîne légère / Cadena ligera
DVVMTQSPLS LPVTLGQPAS ISCRSSQSLI YSDGNAYLHW FLQKPGQSPR 50
LLIYKVSNRF SGVPDRFSGS GSGTDFTLKI SRVEAEDVGV YYCSQSTHVP 100
WTFGQGTKVE IKRTVAAPSV FIFPPSDEQL KSGTASVVCL LNNFYPREAK 150
VQWKVDNALQ SGNSQESVTE QDSKDSTYSL SSTLTLSKAD YEKHKVYACE 200
VTHQGLSSPV TKSFNRGEC 219
Disulfide bridges location / Position des ponts disulfure / Posiciones de los puentes disulfuro
Intra-H 22-96 139-195 256-316 362-420
22”-96” 139”-195” 256”-316” 362”-420”
Intra-L 23′-93′ 139′-199′
23”’-93”’ 139”’-199”’
Inter-H-L 215-219′ 215”-219”’
Inter-H-H 221-221” 224-224”
N-glycosylation sites / Sites de N-glycosylation / Posiciones de N-glicosilación
292, 292

The market for Alzheimer’s disease therapies is set to nearly triple between 2012 and 2022, despite increasing genericisation and the fact that few new product launches are expected during this time, according to new forecasts.

The key driver of growth in the AD market will be Eli Lilly’s anti-beta-amyloid monoclonal antibody solanezumab, the first potentially disease-modifying therapy (DMT) to launch for AD, according to the study, from Decision Resources. It reports that solanezumab is expected to launch in the seven major pharmaceutical markets – the US, France, Germany, Italy, Spain, the UK and Japan – starting in 2018 and that, by 2022, the drug is forecast to attain sales in excess of $5 billion in these markets.

More than 85% of solanezumab’s projected total use in 2022 will be in the mild AD market – the population in which the drug is currently being tested – followed by the pre-AD 1-2 years market segment, says the firm, which defines this latter population as those patients who will go on to develop overt AD within the next one to two years.

Solanezumab (proposed INN) is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector^[1] for patients withAlzheimer’s disease.^[2][3]

It binds to the amyloid-β peptides that make up the protein plaques seen in the brains of people with the disease.

2012 results of the EXPEDITION 1 & 2 phase 3 clinical trials were only mildly encouraging.^[4][5][6] but were said to be the “first evidence that targeting the amyloid cascade can slow the progression of disease.”^[7]

1.  International Nonproprietary Names for Pharmaceutical Substances (INN, prepublication copy), World Health Organization.
2.  ClinicalTrials.gov NCT00749216 Solanezumab Safety Study in Japanese Patients With Alzheimer’s Disease
3.  ClinicalTrials.gov NCT00905372 Effect of LY2062430 on the Progression of Alzheimer’s Disease (EXPEDITION)
4.  “Lilly’s Solanezumab Slows Down Alzheimer’s Progression”. 9 Oct 2012.
5.  Solanezumab Did it actually work
6.  “Eli Lilly’s solanezumab faces grim prospects of attaining conditional FDA approval in mild Alzheimer’s”. 4 Sep 2012.
7. “ALZHEIMER’S DRUG SLOWS MEMORY LOSS BY ONE THIRD”. 10 Oct 2012.

yellow coloured SOLANEZUMAB blocks beta amyloid from aa 16 to aa 25

Amyloid precursor protein (APP)