Fujifilm acknowledged today that its Alzheimer’s disease drug candidate T-817MA has failed a Phase II trial—the latest in a long string of potential treatments to miss in clinical studies—though the company vowed that it would continue to develop the drug.
T-817MA missed its primary endpoints of cognition or global clinical function in the trial, conducted in the U.S. in patients with mild to moderate forms of the memory-robbing ailment. The study also saw no significant differences in secondary outcomes, Fujifilm said.
The company, however, cited exploratory analyses which found that changes to the cerebrospinal fluid biomarker phospho-tau (p-Tau) benefited from the higher-dose treatment while hippocampal volumes showed statistically significant smaller decreases among patients with lower doses of T-817MA.
Also potentially promising, Fujifilm added, were post hoc analyses that associated statistically significant better cognitive outcomes with T-817MA treatment in patients with shorter durations of illness and symptoms.
“Fujifilm will review the results of the Phase II clinical trial with regulatory authorities including the FDA, and will take necessary steps toward further development including Phase III clinical trial of this compound,” the company said in a statement.
To that end, Fujifilm said it may pursue “possible partnerships” aimed at development of T-817MA, which is designed to promote neurite outgrowth through activation of sigma receptors, and which had shown effectiveness in animal models.
T-817MA was discovered by Fujifilm’s Toyama Chemical subsidiary. In preclinical research, T-817MA was shown to act on microglia with a risk gene for Alzheimer’s by promoting the clearance of the amyloid-β (Aβ) protein. These results, according to Fujifilm, suggested that T-817MA may act on p-Tau and Aβ, major causal substances in the disease.
Struggling to Develop New Drugs
T-817MA is the latest Alzheimer’s candidate by a major biopharma to fail in clinical trials. Developers have long struggled to create successful new drugs for Alzheimer’s. Only a handful of drug successes have ever reached the market, and even they have merely slowed progression of symptoms by 6 to 12 months.
A 2014 Cleveland Clinic study found a 99.6% failure rate of clinical trials for Alzheimer's drug candidates between 2002 and 2012. That study found high attrition rates for Alzheimer’s treatments, with 72% of agents failing in Phase I, 92% failing in Phase II, and 98% failing in Phase III.
“The high rate of attrition of compounds requires a constant supply of new approaches (new chemical entities, immunotherapies, repurposed drugs, devices) that can be assessed for efficacy in Alzheimer's disease,” Jeffrey L. Cummings, M.D., Sc.D., of the Cleveland Clinic, and colleagues, concluded.
In February, Merck & Co. halted a pivotal Phase II/III study of its Alzheimer’s disease candidate verubecestat after the trial’s external Data Monitoring Committee advised that the potential treatment was unlikely to demonstrate any positive clinical benefit.
Two failures occurred late last year: Lundbeck acknowledged in September 2016 that the Alzheimer’s candidate idalopirdine, which it had been developing through a partnership with Otsuka Pharmaceutical, failed its first Phase III trial by failing to show efficacy in patients with mild to moderate forms of the disease.
Two months later, Eli Lilly disclosed the Phase III trial failure of its drug candidate solanezumab in patients with mild dementia due to Alzheimer's disease. Lilly followed up by revealing plans in January to eliminate about 485 field-based employees based in its Integrated Health Partners (IHP)/Cardiovascular Account Specialists organization within the company’s U.S. Bio-Medicines Business Unit.