Announcing the results of its phase I study of CTS-21166, a disease-modifying treatment for Alzheimer's, CoMentis, Inc., said the study indicated CTS-21166 as safe and well tolerated. CTS-21166 is the proprietary, orally bioavailable, small-molecule beta-secretase inhibitor developed by the biopharmaceutical company.
Results from the study indicate that CTS-21166 is safe and well-tolerated. Pharmacodynamic proof of activity was achieved as subjects displayed a robust, sustained and dose-related reduction in plasma amyloid beta in both area-under-curve (AUC) reduction and peak reduction with effects lasting over 72 hours. Single dose administration of CTS-21166 produced a greater than 60 per cent reduction of plasma amyloid beta measured either by AUC over 24 hours or as a maximal reduction relative to predose levels. The top doses of CTS-21166 further demonstrated a sustained reduction in AUC that was greater than 40 per cent over 72 hours.
"These data represent a significant advancement in the development of novel therapeutics to treat Alzheimer's disease. CTS-21166 produced a rapid and significant reduction of plasma amyloid beta, a key biomarker that is believed to be involved in the pathogenesis of Alzheimer's disease," said Henry Hsu, M.D, chief medical officer, CoMentis. "CTS-21166 represents an entirely new approach to the treatment of Alzheimer's disease by inhibiting beta-secretase, an enzyme critical in the production of potentially toxic amyloid beta. It has the potential to become the first-in-class disease modifying therapeutic agent."
The phase I trial in healthy volunteers was designed as a dose escalation study to assess the safety, tolerability and pharmacokinetics and pharmacodynamics of CTS-21166 following intravenous administration. Forty-eight subjects received one of six different doses or placebo. The study measured levels of CTS-21166 and levels of amyloid beta in the plasma. CTS-21166 demonstrated excellent pharmacokinetic properties including dose proportional exposure and very low inter-subject pharmacokinetic variability. In addition, the pharmacokinetic profile is consistent with once a day dosing and will support a commercial product.
"We are very excited about the potential of our beta-secretase inhibitor platform and we anticipate launching a phase II study of oral CTS-21166 in Alzheimer's patients in 2008," said W. Scott Harkonen, M.D., president and chief executive officer, CoMentis. "In an effort to accelerate the development of this platform, we are in advanced partnership negotiations with multiple parties and we expect to complete a transaction during the first quarter of 2008."
Inhibition of beta-secretase reduces amyloid beta production and could slow the progression of Alzheimer's disease. CTS-21166 is the first of several highly selective, potent and orally active beta-secretase inhibitors being developed by CoMentis that show excellent efficacy in preclinical models of Alzheimer's disease.
CoMentis, Inc. is engaged in the discovery and development of small-molecule drugs to treat Alzheimer's disease, age-related macular degeneration (AMD) and cognitive disorders. The company has two fundamental technology platforms: (i) aspartic protease inhibitors, including beta-secretase inhibitors for Alzheimer's disease; and (ii) nicotinic acetylcholine receptor (nAChR) agonists and antagonists for the treatment of angiogenesis mediated diseases and cognitive disorders.