Background
Dementia affects more than 9 million people in the European Union, with numbers projected to rise by nearly 60% by 2050. As the most common cause of dementia by far, Alzheimer’s disease (AD) has been a major focus of research efforts to identify new treatments. Recent clinical trials of anti-amyloid therapies have marked a turning point for the field, demonstrating a statistically significant slowing of clinical decline for participants receiving treatment, compared to those receiving a placebo.
Another experimental AD candidate drug, blarcamesine, which is an orally-administered small molecule, represents a different therapeutic approach compared to anti-amyloid antibodies, as a daily, oral medication that does not require intravenous infusions or brain scans for safety monitoring. Rather than targeting plaques directly, blarcamesine is designed to restore cellular homeostasis by activating the sigma-1 receptor (SIGMAR1), which promotes cellular homeostasis and autophagy, and thereby slow neurodegenerative pro-cesses upstream of amyloid and tau pathology.
Based on the results of the Phase Ib/III ANAVEX2-73-AD-004 trial, supported by longer-term follow-up in the open-label extension ATTENTION-AD study, Anavex Life Sciences submitted a marketing authorisation application for the drug to the European Medicines Agency (EMA) in November 2024. ANAVEX2-73-AD-004 was a randomised, placebo-controlled trial with 462 participants aged between 60 and 85, who received a once-daily oral dose of blarcamesine. On 11 December 2025, the EMA’s Committee for Medicinal Products for Human use (CHMP) issued a negative opinion on the marketing authorisation application of Anavex for blarcamesine, for the treatment of early AD (defined as mild cognitive impairment or mild dementia due to AD).
The CHMP recommended refusal of the application on the basis that the main study failed to demonstrate effectiveness and safety of blarcamesine in people with early AD who do not have a mutation in the SIG-MAR1 gene. The CHMP noted methodological issues in the data which raised concerns about the validity of the results. The CHMP also noted that a high proportion of patients stopped treatment during the main study, mainly due to side effects related to the central nervous system (e.g. dizziness), which raised con-cerns about how well the medicine is tolerated.
On 17 December 2025, Anavex requested a re-examination of the negative opinion for blarcamesine.
Alzheimer Europe’s response to the negative opinion of the CHMP
Alzheimer Europe understands the CHMP view that the provided efficacy and safety data may have been insufficient to recommend a full marketing authorisation for blarcamesine. However, the organisation would strongly support the granting of a conditional marketing authorisation with an obligation for the company to conduct an additional phase III clinical trial and to collect real world evidence from patients being treated in European countries.
Alzheimer Europe feels that the data provided by the company meets the requirements for such a conditional marketing authorisation, namely:
- the medicine fulfils an unmet medical need
- the benefit-risk balance of the medicine is positive,
- the company can be required to provide comprehensive data post-authorisation and
- the benefit of the medicine's immediate availability to patients is greater than the risk inherent in the fact that additional data is still required.
Alzheimer Europe therefore hopes that the re-examination will result in a decision that will allow people with early AD in Europe to access another treatment option with stringent eligibility criteria and efficient monitoring of side effects to ensure patient safety.
This position statement, issued in response to the CHMP opinion, identifies the following key reasons for Alzheimer Europe and its member organisations to support a conditional approval of blarcamesine.
The full document is available for reading or downloading below.