INmune Bio’s stock plunged by more than 50% after its TNF inhibitor failed to demonstrate efficacy in Alzheimer’s patients during a Phase II study.
The Phase II MINDFuL trial (NCT05318976) was evaluating XPro (pegipanermin), a selective soluble TNF inhibitor, in patients with early Alzheimer’s with biomarkers of inflammation.
In the intent-to-treat population, no benefit was seen at the six-month evaluation point, however a 0.27 point improvement on the primary endpoint of Early Mild Alzheimer’s Cognitive Composite (EMACC), as well a -0.20 point change in pTau217 blood levels was seen in early Alzheimer’s patients with two or more biomarkers of inflammation at baseline. INmune Bio says that this shows a population that could benefit from XPro.
INmune Bio added that XPro remained safe and well tolerated in the study, with no occurrences of ARIA-E or ARIA-H, a common adverse event (AE) associated with Alzheimer's disease therapies. Injection site reactions were more common in the XPro group, with ten patients discontinuing treatment in the XPro group due to reactions.
As a result, US-based INmune Bio plans to engage with regulatory authorities regarding a pivotal study of XPro in the patient population, and intends to submit an application to the US Food and Drug Administration (FDA) for breakthrough therapy designation.
Neuropsychologist Dr Judith Jaeger, who has worked as a consultant to INmune Bio in the study, said: “In early-phase Alzheimer’s disease trials, absolute effect sizes of 0.2 or greater are considered preliminary evidence of potential therapeutic efficacy and are informative for signal detection in early phase studies when sample sizes are small and the unknowns of a novel mechanism are significant.
"When a therapy consistently meets the 0.2 benchmark across multiple parameters (clinical and biological), confidence in the validity of the observed effects increases, indicating a therapy is worth advancing.”
Despite INmune Bio’s optimistic view of the data, investors remain unconvinced, with the company’s stock dropping by 56.6% to $2.02 on 30 June.
Additional data from the study is set to be presented at the Alzheimer's Association International Conference (AAIC) in Toronto, Canada, on 27-31 July.
The Phase II trial came to a close 12 months after a lengthy FDA clinical hold was lifted. The FDA placed the study in a clinical hold in May 2022 due to manufacturing issues. The hold was lifted in January 2024.
The Alzheimer’s disease treatment space is proving difficult to break into, with just a handful of approved therapies. These include Eli Lilly’s Kisunla (donanemab) and Eisai and Biogen’s Leqembi (lecanemab), both of which are monoclonal antibodies that remove amyloid beta (Aβ) plaques from the brain.
Both therapies are approved in the US and UK after showing clinical benefit in pivotal trials; however, in the UK, the National Institute for Health and Care Excellence (NICE) has rejected the use of either drug on the NHS, stating that neither provides “good value for money”.
