A phase 3 trial of Accera’s Alzheimer’s disease candidate has missed its primary endpoint. The trial aimed to show Accera’s brain metabolism-focused approach to improving outcomes in Alzheimer’s could succeed where beta-amyloid drugs have failed, but instead ended up becoming yet another late-phase failure.
Accera enrolled more than 400 patients with mild-to-moderate Alzheimer’s and randomized them to receive daily doses of AC-1204 or a placebo. The idea was to improve scores on an Alzheimer’s diseases scale by addressing the slowdown in cerebral metabolism associated with the condition. AC-1204 is designed to restore the energy supply to the brain by giving it a source of ketones to top up the dwindling power it derives from glucose.
In phase 2b, a subgroup analysis of patients who lack the APOE4 gene gave Accera the confidence to move into phase 3. But, like many big names before it, Accera has found it impossible to turn a hint of potential in phase 2 into success in phase 3. Accera, again following a well trodden path, is refusing to let the setback scuttle the program, though.
“The formulation of the drug was changed between the phase 2 and phase 3 studies. Unfortunately, this change in formulation had the unintended consequence of lowering drug levels in patients. We are confident that our newly developed formulation will provide increased exposure and allow a more conclusive test of drug efficacy,” Accera VP of R&D Samuel Henderson, Ph.D., said in a statement.
Prior to the results from the first phase 3, Accera was gearing up to start a second late-stage study that would tee it up to win approval in 2020. The plan now is to finalize the clinical development strategy for AC-1204 and discuss next steps with FDA.
That will put Accera in the room with an agency that has slammed some of its activities. Accera began life as a developer of Axona, a product it marketed as a medical food for use in Alzheimer’s. FDA hit Accera with a warning letter in 2013 on the grounds its marketing materials caused Axona to be classed as a drug. Accera continues to market Axona as a medical food for Alzheimer’s, but has tweaked its website since the warning letter.
Axona and AC-1204 both provide patients with a source of caprylic triglyceride—also known as fractionated coconut oil—that is intended to increase the availability of ketones to the brain. The potential of the therapeutic approach has enabled Accera to pull in more than $150 million from backers including Nestlé, according to SEC filings.