Fujifilm Starts Phase II Clinical Trial of T-817MA in Europe for Treatment of Alzheimer Disease
For Patients with Mild Cognitive Impairment and Mild Alzheimer Disease
December 25, 2019
Tokyo ― FUJIFILM Corporation (President: Kenji Sukeno) announced the start of a Phase II Clinical Trial of T-817MA* for the treatment of Alzheimer disease (“AD”) in Europe. This trial targets early AD patients with mild cognitive impairment※1 and mild AD.
AD is an irreversible, progressive brain disorder with main symptoms of abnormalities in cognitive functions such as memory. Currently, it has been revealed that abnormalities in the brain such as the accumulation of fibrous amyloid β protein and neurofibrillary tangles caused by hyperphosphorylation of tau proteins (p-tau), synapse※2 loss, neuronal cell death, and atrophy of the brain are deeply related to the progression of AD, and these abnormalities occur prior to the onset of AD. It has been reported that phosphorylated tau accumulation and cognitive decline correlate significantly, suggesting that phosphorylated tau accumulation plays an important role in the progression of AD.
T-817MA is an AD drug candidate created by FUJIFILM Toyama Chemical Co., Ltd. It has neuroprotective effects and promotes neurite outgrowth. In a US phase II clinical trial on patients with mild to moderate AD that was started in 2014, the reduction in p-tau was observed compared to placebo group in the patient group whose cerebrospinal fluid (CSF) could be obtained.
Based on the results of previous clinical trials, Fujifilm has set the primary endpoint to the change in p-tau in the cerebrospinal fluid in 18 months from the start of administration for this time. Since early intervention in AD is important, this clinical trial will assess the efficacy and safety of T-817MA on patients of early AD with abnormal levels of AD biomarkers※3 such as amyloid β and p-tau.
T-817MA also acts upon microglial cells※4 that are drawing interest as a new target for AD drugs, and the compound promoted microglial cell’s phagocytosis of amyloid β in mouse and human iPS cell derived cell experiments. In addition to clinical development, Fujifilm will work to further elucidate the relationship between T-817MA and phospho-tau, amyloid β, and microglial cells, which are the main causal substances of AD.
Fujifilm will contribute to resolving social challenges through the creation of innovative and high value-added pharmaceutical products, actively promoting new drug development in the areas of “oncology”, “central nervous system diseases”, and “infectious diseases”, where there are high unmet medical needs.
※1 The precursor stage to AD characterized by mild symptoms of memory impairment such as forgetfulness.
※2 Structures that connect neurons and play a central role in the transmission of information between neurons. When a neuron is activated, neurotransmitters released from the presynaptic terminal of the neuron bind to receptors in the synapse of another neuron, conveying information.
※3 Indices that are objectively measured and evaluated as indicators of pharmacological response in diagnostic imaging data such as MRIs and clinical test values in blood tests.
※4 A type of glial cell that is responsible for maintaining homeostasis in the brain. Ordinarily, microglial cells promote phagocytosis of amyloid β accumulated in the brain and promote the regeneration of nerve cells, however, when abnormally activated, they promote inflammation in the brain, such as releasing inflammatory cytokines that cause neuronal cell death.
T-817MA is a candidate compound for an AD drug created by FUJIFILM Toyama Chemical Co., Ltd. Research results have been reported that suggest diverse properties of T-817MA such as the prevention of neuronal cell death due to various kinds of stress, suppression of the inflammatory response through the adjustment of microglial cell function, and promotion of the building of new nerve cell networks. Based on these results, in addition to the development for treatment of Alzheimer disease, the Fujifilm Group is also promoting the development of T-817MA into a new drug that promotes the effects of rehabilitation after a stroke.
*Products described herein are investigational products and not approved by the U.S. Food & Drug Administration