Digging into a prespecified analysis for the mid-stage study, INmune Bio identified some clinical and biological benefits of its TNF inhibitor in patients with early Alzheimer’s disease who have at least two biomarkers of inflammation.
INmune Bio’s investigational TNF inhibitor XPro showed no significant cognitive benefit in a mid-stage trial when used to treat patients with early Alzheimer’s disease who show signs of inflammation.
These findings come from the Phase II MINDFuL study, which enrolled some 200 patients with early-stage disease and biomarkers of neuroinflammation. In the trial’s modified intention-to-treat analysis, XPro over six months failed to significantly boost cognition over placebo, as measured by the Early Mild Alzheimer’s Cognitive Composite (EMACC), an assessment tool specifically meant for early Alzheimer’s disease (AD).
INmune was down by as much as 60% before the opening bell on Monday.
Despite falling short of its primary efficacy endpoint, the Florida-based biotech remained confident in the “potential” of XPro as a “promising treatment option” for Alzheimer’s, CEO RJ Tesi said in a statement.
Digging into a prespecified analysis of 100 patients who had at least two inflammatory biomarkers, INmune touted a “clinical benefit” for XPro over placebo on the EMACC. Results had an effect size of 0.27, which, according to Judith Jaeger, founder and president of CognitionMetrics and principal developer of EMACC, can be “considered preliminary evidence of potential therapeutic efficacy and are informative for signal detection in early phase studies.” Jaeger served as a consultant to INmune on the MINDFuL study.
Additionally, in this prespecified cohort, the company detected a “biological benefit” of XPro, as measured by a drop in the blood levels of the tau protein, which it called “the gold standard measure of AD pathology in blood.”
As for safety, INmune reported no instances of amyloid-related imaging abnormalities (ARIA) indicative of swelling or bleeding. Eight in 10 patients dosed with XPro developed injection-site reactions, as opposed to fewer than 20% of placebo counterparts. MINDFuL detected no deaths, organ system toxicities or drug-related hospitalizations.
Following Monday’s data drop, INmune plans to file for an FDA Breakthrough Therapy designation for XPro. An end-of-Phase II meeting with the agency is scheduled for the fourth quarter, after which the company expects to have more clarity on moving the drug forward.
Alzheimer’s remains a difficult disease to address. Currently, there are two FDA-approved therapies: Biogen and Eisai’s Leqembi and Eli Lilly’s Kisunla. While the drugs have been on the market since January 2023 and July 2024, respectively, their uptake has been slow amid continued criticism regarding their safety and efficacy.
In late March, for instance, the European Union’s Committee for Medicinal Products for Human Use (CHMP) refused to endorse Kisunla for approval in the region, citing safety concerns that the drug’s potential therapeutic benefits do not outweigh.
Meanwhile, while the CHMP has signed off on Leqembi, the U.K.’s National Institute for Health and Care Excellence has not—the agency in March did not recommend the antibody for coverage by the National Health Service, contending that its benefits are “too small to justify the cost.” Leqembi has also struggled to take off in the U.S., with Eisai being forced to lower its sales projection for the therapy again and again.
