New Alzheimer’s data from Cognition Therapeutics appeared to show an early drug effect, but one that lessened over time.
Cognition presented Phase 2 results from two dose cohorts comparing its oral Alzheimer’s program CT1812 to placebo. In the low-dose cohort, CT1812 improved cognition by a statistically significant margin after 98 days, inducing a -1.79 difference between the active and placebo arms on an Alzheimer’s cognition score called ADAS-Cog 11 (p-value of p=0.0430).
But at the six-month mark, that effect had waned, with the ADAS-Cog 11 score difference shrinking to -0.99 points. The p-value at this time point was p=0.3835. Additionally, the scores also worsened in the trial’s high-dose group, from -1.35 points at day 98 to -1.10 at day 182. Neither of those p-values (p=0.1410, p=0.3641) were statistically significant.
Cognition’s stock price $CGTX fell about 40% after Monday’s opening bell. The company reported its results at the 2024 Alzheimer’s Association International Conference in Philadelphia.
Lisa RicciardiCMO Anthony Caggiano said on an investor call that a rapid onset had been expected, but longer studies would be needed to determine the potential for the slowing of neurodegeneration. CEO Lisa Ricciardi added that the company is planning to design a pivotal study and raise cash to conduct it, but the trial protocols are still being discussed.
“We’re optimistic that when we do those studies that are a longer time, you’ll see that effect maintained, or perhaps even extended,” Caggiano said.
The primary endpoint of the study was safety, which was achieved, Cognition said. Researchers saw no symptomatic brain bleeding events, also known as ARIA. Five patients taking either dose experienced at least one serious side effect, as did five individuals taking placebo. Nine patients in the high-dose group experienced elevated liver enzymes, compared to none in the low-dose group.
CT1812 also appeared to show a dose response in a biomarker called neurofilament light chain, which has seen increased interest over the past few years in other neurodegenerative diseases like ALS. Reductions in the high-dose group compared to placebo were statistically significant, with a p-value of 0.0277.
The impact of lower neurofilament remains unclear, however, as the biomarker has generally taken a backseat to others in Alzheimer’s disease research like amyloid beta plaque or tau. Ratios of amyloid plaque between the groups were unchanged, and p-tau biomarkers did not approach statistical significance, Cognition said.