Phase 2 SHINE Data Shows Limited Improvement Signals in Alzheimer's

Cognition Therapeutics' phase 2 SHINE trial on the Alzheimer’s disease drug candidate CT1812 faced setbacks, as the oral sigma-2 antagonist did not statistically outperform the placebo or meet Cognition's set benchmarks for success. The trial, which involved 153 adults with mild to moderate Alzheimer's disease, required participants to take one of two doses of CT1812 or a placebo daily for six months. The primary measure was adverse events, while the key efficacy endpoint focused on ADAS-Cog 11, a tool used to assess cognitive symptoms severity in dementia.

In an earlier report from November 2023, data from the initial 24 patients indicated a promising three-point improvement in ADAS-Cog 11 scores. Cognition CEO Lisa Ricciardi had highlighted this preliminary success at a Needham investor event in April, emphasizing the importance of replicating these early results in the full trial to signify success.

However, the final data did not replicate this initial optimism, showing less than a one-point difference between the placebo and treatment groups after 182 days. Specifically, ADAS-Cog 11 scores worsened by 2.7 points in the placebo group compared to a 1.66-point decline in the CT1812 group, leading to a difference of just 1.04 points. Despite the modest results, Cognition framed these findings as a 39% slowing of cognitive decline favoring CT1812, comparing it to other approved drugs.

Ricciardi commented that these results were similar to those achieved with currently approved antibody treatments, highlighting the ease of administering CT1812 as a once-daily oral dose with less burden for patients. Nevertheless, Ricciardi had higher expectations for the drug, believing it could demonstrate a more significant impact on cognition due to differences in study populations. She speculated that more advanced patients, who typically decline more quickly, would show greater differences in cognitive measures.

Despite not hitting the primary efficacy endpoint, Cognition highlighted statistically significant improvements in ADAS-Cog 11 after 98 days and other cognitive impairment measures throughout the trial. According to the press release, CT1812 consistently showed trends of cognitive improvement compared to placebo across all cognitive measures, with signals of improvement in functional measures as well.

The efficacy data were derived from a pooled analysis of both the low 100-mg dose and the high 300-mg dose, with the 100-mg dose showing a particularly favorable safety and tolerability profile. Cognition plans to move forward with the low dose in additional clinical trials.

Financially, Cognition ended March with $34.7 million in cash and equivalents and $62.3 million remaining from National Institute on Aging grants. The company’s shares fell by 15% to approximately $2.04 in pre-market trading on Monday, down from a prior close of $2.37.