Johnson & Johnson’s Janssen Biotech said it will halt two clinical studies assessing its Alzheimer’s disease candidate atabecestat (JNJ-54861911), citing an unfavorable risk–benefit profile for the β-site amyloid precursor protein-cleaving enzyme (BACE) inhibitor.
Janssen said it will stop screening, randomization, and dosing of atabecestat in its Phase IIb/III EARLY trial (NCT02569398) assessing the drug in late-onset preclinical-stage Alzheimer’s, as well as in a Phase II European long-term safety study (EudraCT Number 2014-004274-41).
Both studies began in 2015, with the EARLY trial having an estimated primary completion date of April 10, 2024.
“Elevations of liver enzymes, which were serious in nature, have been observed in some study participants who received the Janssen BACE inhibitor, atabecestat,” Janssen said in a statement last night. “After a thorough evaluation of all available liver safety data from our studies, Janssen has concluded that the benefit–risk ratio is no longer favorable to continue development of atabecestat for people who have late-onset preclinical-stage Alzheimer’s disease.”
More than 600 people have received the study drug or placebo in these clinical trials, Janssen said.
The company added that it will alert clinical trial investigators, study participants, health authorities, ethics committees, and institutional review boards of its decision.
Janssen is the latest drug developer to stumble in the long struggle 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.
This year alone, drug developers compelled to scrap trials or development programs of Alzheimer’s candidates have included vTv Therapeutics, whose lead candidate azeliragon failed a Phase III study, causing the company’s shares to plunge more than 70%, and Eli Lilly, whose solanezumab did not significantly slow cognitive decline in a Phase III trial with a total 2129 participants with mild dementia due to Alzheimer’s, according to a study published January 25 in the New England Journal of Medicine.
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.