Interview: The US company appealing Europe’s rejection of daily Alzheimer’s pill
Despite having its application for a new, daily Alzheimer’s pill rejected by Europe’s regulators the CEO of US drug company Anavex Life Sciences is appealing this decision.
A Phase IIb/III trial found over one-third of patients with mild Alzheimer’s – those with a Mini-Mental State Examination (MMSE) score of between 20 and 28 – experienced a slowing of their ‘cognitive decline’.
And, for the majority of the population – those with the common sigma-1 gene – the results were even more dramatic, slowing decline by 49.8%.
Despite this success, in December last year, the European medical authorities rejected an application for the drug – known as Blarcamesine – saying the study ‘failed to demonstrate effectiveness and safety’.
Within days Anavex initiated a challenge to the decision. It has called for a re-examination of the evidence and this is now being undertaken by the European Medicines Agency (EMA).
Speaking to Agetech World Dr Christopher Missling, president and CEO of Anavex, said: “The trial data showed that patients actually improved their quality of life.
“The Alzheimer’s patients had a higher quality of life at the end of the trial than at baseline.”
What Is Blarcamesine?
Unlike other treatments targeting Alzheimer antagonists, such as amyloid-beta or tau pathology, Blarcamesine acts upstream by activating sigma-1 receptors.
This permits the restoration of autophagy – the intracellular recycling and cleaning system which is impaired in pathologies such as Alzheimer’s.
Alzheimer treatments such as Leqembi – which has been approved in over 50 counties and targets amyloid-beta plaques in the brain to slow Alzheimer progression – require regular hospital infusions and carry the risk of brain swelling and bleeding.
Blarcamesine is a pill, taken orally, with no evidence of damaging side effects, such as brain swelling or micro-bleeding, eliminating the need for frequent MRI monitoring required for other drugs.
Dr Missling said: “None of this would be required with Blarcamesine, which is a once-daily, simple oral pill you can ship anywhere.
“The efficacy is also extremely favourable; we see a double or more benefit of cognition and function compared to those injectable antibodies. So, it potentially offers a strong advantage not only in safety and convenience but also in efficacy.”
Why was it rejected by the EU?
A statement from the EMA outlined its position: “In December 2025, EMA’s human medicines committee, the Committee for Medicinal Products for Human Use (CHMP), concluded that the main study failed to demonstrate effectiveness and safety of Blarcamesine Anavex in patients with early Alzheimer’s disease who do not have a mutation in the sigma-1 gene.”
It went on to say that Anavex has requested a ‘re-examination of EMA’s opinion issued on December 11, 2025…(and) the agency will re-examine its opinion and issue a final recommendation’.
Concerns raised by the CHMP focused on trial methodology, possible side effects in the nervous system, and impurities that could potentially cause cancer.
Dr Missling highlighted how a lengthening of the titration process had addressed the mild-dizziness issue and the impurity concerns, which centred on an acceptable threshold for nitrosamines, has also been negated.
And, he highlighted how the amyloid-beta plaque-targeting drugs Leqembi and Kisunla – which have been fully approved in the US – were eventually approved in Europe after a similar re-examination process .
USA application
Anavex has started a dialogue with the US Food and Drug Administration which has requested access to all of its trial data and if approved in the USA it will open-up the potential for global market authorisation.
The potential size of the market for Blarcamesine is huge, with the number of adults suffering from Alzheimer’s disease expected to grow from around 60 million to 150 million by 2050, as the global population ages.
Dr Missling on how Blarcamesine works
“Blarcamesine activates the Sigma-1 receptor in vivo, which has been confirmed in several peer-reviewed publications and established with a PET study demonstrating dose-dependent activation in the brain.
“The sigma-1 is an integral membrane protein involved in restoring cellular homeostasis. It activates an upstream compensatory process – autophagy – through sigma-1 activation.
“Autophagy gets impaired over time during aging and especially during pathologies like Alzheimer’s and Parkinson’s. This is a very important process, which is nothing else but the recycling of neurons who cannot get rid of their ‘trash’, if you like; they have to recycle it. If this mechanism is impaired, those cells eventually die.
“It stands at the top of many cascades of this complex pathology, for example, on top of A-beta aggregation or Tau aggregation.
“That’s why it’s intriguing to try to approach this from a more comprehensive upstream viewpoint.
Blarcamesine is a small molecule you can take once a day. It restores homeostasis, reactivates impaired autophagy, and lets the body function as it does in a healthy fashion.”
