Wnt modulators in the biotech pipeline.
Rey JP, Ellies DL
Dev. Dyn. Jan 2010
PMID: 20014100 | Free Full Text
A more favorable approach to the modulation of the Wnt pathway has been to focus on extracellular mediators of the pathway. Where, Amgen is the first in class to develop a biologic therapeutic against Sclerostin (Human Clinical Phase II). Nuvelo is following Amgen with biologics against LRP5, Dkk1, and R-Spondin (Discovery). Second in class for Sclerostin blocking antibodies will be Novartis and Eli Lilly (Preclinical). Fibrogen, who is taking a different approach, has developed a biologic against CCN family member CTGF (Preclinical). As for small molecules, OsteoGeneX is first in class to develop a Sclerostin small molecule inhibitor, currently in preclinical and lead optimization. Alternatively to Sclerostin, Galapagos is developing small molecule leads against LRP5 in a partnership with Eli-Lilly (Discovery).
Blosozumab is a new sclerostin inhibitor developed by Eli Lilly. According to Wikipedia:
Phase II trial of a monoclonal human antibody to sclerostin from Eli Lilly had positive effects on post-menopausal women. Monthly treatments of the antibody for one year increased the bone mineral density of the spine and hip by 18 percent and 6 percent, respectively, compared to the placebo group.
Romosozumab is a new Sclerostin Inhibitor from Amgen. Specifically it is a humanized monoclonal antibody that targets sclerostin for the treatment of osteoporosis. According to Wikipedia:
Its use has increased bone growth in preclinical trials in osteoporotic rats and monkeys. In a Phase I study, a single dose of anti-sclerostin antibody from Amgen (Romosozumab) increased bone density in the hip and spine in healthy men and postmenopausal women and the drug was well tolerated. In a Phase II trial, one year of the antibody treatment in osteoporotic women increased bone density more than bisphosphonate and teriparatide treatment….
The Amgen drug is expected to be on the market in 2017 and is predicted to be the gold standard in osteoporosis treatment by 2021.