INmune Bio's Alzheimer's Drug XPro Fails to Meet Primary Endpoint in Phase II Trial

INmune Bio's investigational TNF inhibitor XPro has failed to demonstrate significant cognitive benefits in a Phase II trial for early Alzheimer's disease (AD) patients with signs of inflammation. The announcement, which led to a sharp decline in the company's stock price, highlights the ongoing challenges in developing effective treatments for this devastating neurodegenerative disorder.

Trial Results and Company Response

The Phase II MINDFuL study, which enrolled approximately 200 patients with early-stage AD and biomarkers of neuroinflammation, did not meet its primary efficacy endpoint. Over a six-month period, XPro failed to significantly improve cognition compared to placebo, as measured by the Early Mild Alzheimer's Cognitive Composite (EMACC).

Despite this setback, INmune Bio remains optimistic about XPro's potential. CEO RJ Tesi stated that the company still considers XPro a "promising treatment option" for Alzheimer's. The company is focusing on positive signals from a prespecified analysis of 100 patients with at least two inflammatory biomarkers, where XPro showed a "clinical benefit" over placebo on the EMACC, with an effect size of 0.27.

Safety Profile and Future Plans

The trial reported no instances of amyloid-related imaging abnormalities (ARIA) indicative of swelling or bleeding, a common concern with some AD treatments. However, 80% of patients receiving XPro developed injection-site reactions, compared to less than 20% in the placebo group. No deaths, organ system toxicities, or drug-related hospitalizations were reported.

INmune Bio plans to file for an FDA Breakthrough Therapy designation for XPro and has scheduled an end-of-Phase II meeting with the agency for the fourth quarter. This meeting is expected to provide clarity on the drug's path forward.

Broader Context of Alzheimer's Drug Development

The challenges faced by INmune Bio's XPro underscore the difficulties in developing effective Alzheimer's treatments. Currently, only two FDA-approved therapies exist for AD: Biogen and Eisai's Leqembi, and Eli Lilly's Kisunla. Both drugs have faced slow uptake and continued scrutiny regarding their safety and efficacy.

Recent developments in Europe highlight the ongoing debate surrounding these treatments. The European Union's Committee for Medicinal Products for Human Use (CHMP) refused to endorse Kisunla for approval, citing safety concerns. While Leqembi received CHMP approval, the UK's National Institute for Health and Care Excellence did not recommend it for coverage by the National Health Service, arguing that its benefits were too small to justify the cost.

As the pharmaceutical industry continues to grapple with the complexities of Alzheimer's disease, the setback for INmune Bio's XPro serves as a reminder of the steep challenges facing researchers and companies in this field. The search for safe, effective, and economically viable treatments for Alzheimer's disease remains an urgent priority for the global healthcare community.