TTP488 slows cognitive decline in patients with mild to moderate Alzheimer's

A novel, orally administered drug candidate, TTP488, has demonstrated clinical evidence of slowing of cognitive decline over 18 months of therapy in patients with mild to moderate Alzheimer's disease. TTP488 is a small-molecule drug that is the first to show clinical benefit from research on the receptor for advanced glycation endproducts (RAGE), a new biochemical target in Alzheimer's disease treatment. TransTech Pharma, Inc. of High Point, North Carolina discovered, developed and owns all rights to this drug candidate.

These new clinical results arise out of a trial sponsored by Pfizer, Inc., and conducted by the Alzheimer's Disease Cooperative Study, a national research consortium funded by the National Institute on Aging, a part of the National Institutes of Health. The trial involved 399 patients with mild to moderate Alzheimer's disease at over 40 of the country's leading teaching hospitals involved in Alzheimer's research.

Analysis, by TransTech Pharma and third-party experts, of the study data reveals a 26% benefit relative to placebo in cognitive decline over 18 months in the group that received a 5 mg dose of TTP488. A more pronounced effect was observed in subjects with mild Alzheimer's disease, who showed a 46% benefit over placebo.

"At present, no FDA-approved drug has been shown to stop, prevent or alter the course of cognitive decline in patients with Alzheimer's disease," said Dr. Adnan Mjalli, Chairman and Chief Executive Officer of TransTech Pharma. "We are very excited about this data, which may lead to an approvable, novel treatment for millions of patients suffering from Alzheimer's disease here in the United States and around the globe. Because demand remains high for a treatment that can preserve cognitive function in this population, TransTech Pharma will be exploring options for accelerated FDA approval of this novel Alzheimer's treatment."

Dr. Mjalli added his thoughts concerning the drug's novel target, RAGE. "Exploiting the RAGE pathway offers a completely new approach to the treatment of Alzheimer's disease. Mechanistically, TTP488 acts, in part, by restoring the normal balance of amyloid protein transport into and out of the brain. Restoring this natural balance in patients with Alzheimer's disease, who have diminished capacity to clear amyloid protein from the brain, may result in long-term disease modification and maintenance of cognitive function."

"Given the recent failure of bapineuzumab and the inconclusive results of solanezumab, TTP488 is emerging as a promising new drug for the treatment of Alzheimer's disease in clinical development. RAGE antagonists have been of interest for some time. These exciting phase IIb results of TTP488 on top of optimal standard background therapy are encouraging and, with further study, could lead to a new treatment for Alzheimer's disease," commented Marwan Sabbagh MD, FAAN, Director, Banner Sun Health Research Institute, Research Professor of Neurology, University of Arizona College of Medicine-Phoenix and participating investigator in the TTP488 study.

"We are encouraged by the results of this study," said Cesare Orlandi, MD, Senior Vice President and Chief Medical Officer of TransTech Pharma. "Statistical analysis of the data from this study, including execution of the pre-specified primary analyses following regulatory standards, resulted in significant p-values. Extensive post-hoc analyses also revealed a consistent signal indicative of a therapeutic benefit at the 5 mg dose level involved in this study. The magnitude of the observed effect in the subpopulation suffering from mild Alzheimer's disease is of particularly great interest. This finding will allow us to optimize the design of future studies."

TransTech Pharma believes that the benefits observable in the data collected in the clinical trial did not support the decision by Pfizer, Inc., to halt the trial prior to its intended completion. For example, although individuals enrolled in the trial at the highest tested dose experienced signs of toxicity, those effects were reversible, and the lower dose resulted in the benefits and lack of adverse events reported here.

Douglas Galasko, the principal investigator at the University of California, San Diego, for the Alzheimer's Disease Cooperative Study, suggested "Stopping the study early in accordance with a pre-specified futility analysis may have been premature. In light of the benefit of low dose TTP488 on cognitive decline important additional data could have been collected."