On 12 December 2025, the Committee for Medicinal Products for Human use (CHMP) of the European Medicines Agency (EMA) issued a negative opinion on the marketing authorisation application of Anavex for blarcamesine, for the treatment of early Alzheimer’s disease, in people who do not have a mutation in the gene for SIGMAR-1. Blarcamesine is a small molecule drug, delivered as a daily, oral capsule, which is designed to enhance autophagy, a cellular process that removes damaging waste products from the brain. It does so by activating the SIGMAR-1 protein, which helps regulate autophagy.
The CHMP recommended refusal of the marketing authorisation application, concluding that the evidence presented did not sufficiently demonstrate effectiveness of the medicine, and that safety could not be adequately characterised.
During their assessment, the CHMP considered data from 462 participants in ANAVEX2-73-AD-004, a Phase 2b/3 clinical trial investigating blarcamesine for the treatment of early AD (mild cognitive impairment or mild dementia due to AD). ANAVEX2-73-AD-004 was a randomised, double-blind and placebo-controlled study that involved participants from five countries in north America and Europe. Trial results, which were published in a scientific journal in January 2025, showed that blarcamesine slowed clinical progression by 36.3% on the ADAS-Cog13 scale of cognition after 48 weeks of treatment, while ADCS-ADL, the co-primary endpoint measuring activities of daily living, did not reach statistical significance. Blarcamesine demonstrated a favourable safety profile with no amyloid-related imaging abnormalities (ARIA), side effects linked to small bleeds or swelling in the brain. However, transient side effects during the titration phase were fairly common: around 36% of participants reported dizziness while 14% experienced a confusional state.
In their opinion, the CHMP concluded that the main clinical study did not provide clear evidence of benefit across the key measures of cognition and daily functioning. Based on the analysis of the data for the subgroup of trial participants without SIGMAR1 mutations, it was not possible to reach a positive conclusion regarding the effectiveness of the medicine. They also stated that the available safety data were limited, with a number of participants stopping treatment due to side effects, with some unresolved concerns about potential impurities in the medicine. For these reasons, the CHMP recommended refusing the marketing authorisation, although they recognised the ongoing unmet need for treatments for Alzheimer’s disease.
Alzheimer Europe recognises that people living with Alzheimer’s disease and their families had high expectations for new treatment options and will be disappointed that the scientific evidence was considered insufficient to support the authorisation of blarcamesine. Alzheimer Europe hopes that the re-examination request announced by Anavex on 14 November will provide additional evidence for the CHMP to reconsider its position as blarcamesine represents a fundamentally different therapeutic approach compared with anti-amyloid antibodies, as a daily, oral medication that does not require intravenous infusions or brain scans for safety monitoring.
Alzheimer Europe remains encouraged by the number of companies and organisations continuing to invest in research and the new treatment options currently being developed. The organisation therefore reiterates its call for continued research into other treatment options, including symptomatic treatment for people in more advanced stages. In addition, Alzheimer Europe remains committed to a holistic approach to Alzheimer’s disease and other types of dementia where new treatment options are included alongside counselling, support and care of people with dementia and their families throughout the disease process.
You can find details of the CHMP recommendation here: https://www.ema.europa.eu/en/medicines/human/EPAR/blarcamesine-anavex
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For further information, contact: Jean Georges, Executive Director, Alzheimer Europe a.s.b.l, 5, Heienhaff, L-1736 Luxembourg, Tel.: +352-29 79 70, Fax: +352-29 79 72, jean.georges@alzheimer-europe.org, www.alzheimer-europe.org
Notes to editors:
Alzheimer Europe is the umbrella organisation of national Alzheimer associations and currently has 41 member organisations in 36 European countries.
Declaration of interests: Alzheimer Europe had an audited income of EUR 3,126,949 in 2024. Sponsorship by the developing company of blarcamesine (Anavex) in 2025 amounted to EUR25,000 or 0.8% of the organisation’s forecasted income for 2025. Sponsorship by pharmaceutical companies is only accepted in accordance with the organisation’s Sponsorship guidelines and, in line with the European Medicines Agency criteria for patient organisations, declared in full transparency on the Alzheimer Europe website: https://www.alzheimer-europe.org/about-us/governance/finances/alzheimer-europe-sponsors