AB Science SA, of Paris, began a Phase III trial of masitinib, a drug it already has studied broadly in cancer indications, in Alzheimer's disease.
The company documented significant efficacy for masitinib in Phase II as an add-on to standard care over 24 weeks, with improvement in cognitive function and functional capacity in the treatment group, plus sustained and statistically significant response on the Alzheimer's Disease Assessment Cooperative Study Activities on Daily Living (ADAS-ADL).
It is hoping to confirm those results in Phase III, a stage of development that has been the downfall of numerous other Alzheimer's therapies in recent years.
Failures of two Abeta-peptide-targeting antibodies, Eli Lilly and Co.'s solanezumab and Pfizer Inc./Johnson & Johnson/Elan Corp. plc product bapineuzumab have dampened enthusiasm for Alzheimer's therapy and cast a shadow over subsequent late-stage clinical trials. (See BioWorld Today, Aug. 8, 2012, and Aug. 27, 2012.)
Some firms have stumbled earlier. In February, AC Immune SA discontinued development of pirenzepine, a muscarinic acetylocholine inhibitor previously approved in some European countries for ulcers, after it washed out in a Phase II study in Alzheimer's. And a glycogen synthase kinase 2beta inhibitor, tideglusib, by Zeltia SA, of Madrid, Spain, missed its primary endpoint in a Phase IIb trial last year. (See BioWorld Today, Feb. 1, 2013.)
Alzheimer's disease affects about 6 percent of people older than 65, or about 850,000 people in France. It is viewed as an imminently critical public health need due to the aging population in the U.S.
Masitinib is a tyrosine kinase inhibitor that targets mast cells and some kinases that have significance for cancer. Mast cell activity is thought to activate inflammatory cells and affect fibrosing tissue remodeling, giving them significance for inflammatory and central nervous system diseases.
The double-blind, randomized, placebo-controlled trial will assess safety and efficacy of masitinib at two doses after 24 weeks in patients with mild to moderate Alzheimer's disease.
Enrolled patients will have received a minimum of six months treatment with a stable dose of cholinesterase inhibitors and/or memantine.
Efficacy will be determined by ADAS-ADL.
AB Science is studying masitinib in eight different clinical programs. It has Phase III trials ongoing in pancreatic cancer, gastrointestinal stromal tumors (GIST) and mastocytosis. Programs in multiple myeloma, solid tumors, rheumatoid arthritis, asthma and multiple sclerosis are at Phase II.
The company scored a major coup when masitinib outperformed Sutent (sunitinib malate, Pfizer Inc.) in a Phase II head-to-head trial in Gleevec (imatinib, Novartis AG)-resistant GIST.
After 18 months, 79 percent of patients who received masitinib (n = 23) remained alive, compared to just 20 percent of those who received Sutent (n = 21). At 24 months, 53 percent of those in the masitinib arm were alive, and Sutent had no survivors. (See BioWorld Today, Feb. 8, 2012.)