blarcamesine (Anavex 2-73) / Anavex - LARVOL DELTA

Negative opinion for one medicine (European Medicines Agency) - "The committee recommended not granting a marketing authorisation for Blarcamesine Anavex (blarcamesine), a medicine intended for the treatment of Alzheimer’s disease. The CHMP concluded that the main study failed to demonstrate the effectiveness and safety of this medicine in patients with early Alzheimer's disease who do not have mutations in the SIGMAR1 gene."

CHMP • Alzheimer's Disease

Anavex Life Sciences to Present Oral Blarcamesine Data at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference (GlobeNewswire) - "Anavex Life Sciences...will present one oral late breaking communication and two poster presentations....'Blarcamesine demonstrated in early Alzheimer’s disease patients clinically meaningful effects of slowing cognitive decline with an adequate safety profile (no ARIA) as demonstrated in the Phase IIb/III program'..."

Clinical data • Alzheimer's Disease

Blarcamesine (ANAVEX®2–73) Attenuates Spasms and Hypsarrhythmia in a Rat Model of Infantile Epilepsy Spasms Syndrome (AES 2025) - "Current FDA-approved management including adrenocorticotropic hormone (ACTH) and vigabatrin, demonstrate efficacy in only 50–60% of cases and often carry significant side effects, such as immunosuppression and visual field deficits. These results highlight the efficacy of blarcamesine to suppress spasms, ameliorate EEG abnormalities, and prevent progression to spontaneous seizures later during development, advancing approaches for managing IESS."

Preclinical • Absence Seizure Disorder • Cardiovascular • CNS Disorders • Developmental Disorders • Epilepsy • CDKN1A

Expected Development Milestones: (StockTitan.net) - "Regulatory and clinical trial update for blarcamesine in early Alzheimer’s disease, Parkinson’s disease, Rett syndrome; Fragile X development update: Design of Phase 2/3 clinical trial"

Clinical • New P2/3 trial • Regulatory • Alzheimer's Disease • Fragile X Syndrome • Genetic Disorders • Parkinson's Disease

Anavex Retail Traders See Silver Lining In EMA Committee Postpones Alzheimer’s Drug Verdict: Delay ’Actually A Positive Sign’ (StockTwits) - "Anavex later confirmed it had received a negative trend vote following its oral explanation and noted that a formal opinion is expected in December. The company also stated that it plans to request a re-examination once the opinion is issued. The drug was not listed among withdrawn applications, leaving the procedure formally open heading into the next meeting."

CHMP • Alzheimer's Disease

A Systematic Review and Network Meta Analysis of Pharmacologic Disease-Modifying Therapies for Early Alzheimer's Disease (ISPOR-EU 2025) - "Comparators were standard of care (SoC), which may include acetylcholinesterase inhibitors and/or memantine, or any other listed intervention...Following a feasibility assessment, seven RCTs, investigating five DMTs (lecanemab, donanemab, blarcamesine, ALZT-OP1a/1b, and AGB108) were included in the NMA... Several AD DMTs are in the horizon. The RR of SAEs should be considered, when considering alternative AD treatment classes to mitigate the risk of ARIAs."

Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Dementia

Anavex Life Sciences (AVXL, Financial) faces a critical regulatory review by the European Medicines Agency (EMA) for its lead drug, ANAVEX 2-73. (Gurufocus) - "Anavex Life Sciences (AVXL) experienced a significant stock drop of approximately 9% following the European Medicines Agency's (EMA) request for an oral explanation regarding its lead drug, ANAVEX 2-73 (blarcamesine). This drug, aimed at treating Alzheimer's disease and dementia, will be discussed on November 11 at the EMA’s Committee for Medicinal Products for Human Use (CHMP)."

CHMP • Alzheimer's Disease

Anavex Life Sciences Announces Continued Long-Term Benefit from Oral Blarcamesine Compared to Decline Observed in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Control Group (GlobeNewswire) - "Externally matched control participants from the ADNI database were compared with participants over the 144-week period of ANAVEX2-73-AD-004 and its ATTENTION-AD (ANAVEX2-73-AD-EP-004) open-label extension (OLE) Phase IIb/III trial...In the intent-to-treat (ITT) population, significantly less cognitive decline was observed for the blarcamesine participants compared to the ADNI control group at 48 weeks with a significant, and clinically meaningful difference in mean change from baseline ADAS-Cog13 total score of −2.68 points (p < 0.0001)....Over the course of the open-label extension study at time point 96 weeks, these two groups diverged sharply, with statistically significant differences in mean change in ADAS-Cog13 total score at 96 weeks of −6.41 points (p < 0.0001). The difference between groups continues to increase at 144 weeks (ADAS-Cog13 total score difference of −12.78 points; p < 0.0001)."

P2/3 data • Alzheimer's Disease

Presentation title: “Advancing Alzheimer’s Disease Care: Convenience for Both Patients and Families with Oral Blarcamesine” (GlobeNewswire) - "Anavex Life Sciences...announced that Prof. Dr. Timo Grimmer...gave an oral presentation....at the 35th Alzheimer Europe Conference ‘Connecting Science and Communities: The Future of Dementia Care’."

Clinical • Alzheimer's Disease

Receptor subtype specific modulation of muscarinic pathways: a mechanistically distinct therapeutic strategy for schizophrenia (ECNP 2025) - "VU0152100, a selective M4 PAM, exhibits antipsychotic-like effects in rodent models, reducing amphetamine induced locomotor hyperactivity and reversing behavioral deficits...NBI-1117568, a selective M4 orthosteric agonist in Phase 2 trials for schizophrenia, attenuates dopaminergic hyperactivity and restores sensorimotor gating without sedative or motor impairments. Blarcamesine has shown neuroprotective and cognitive enhancing effects in multiple models... Targeting mAChRs, particularly M1 and M4, provides a receptor subtype specific strategy to address unmet needs in schizophrenia. KarXT and emraclidine represent leading agents in clinical development. Emerging modulators such as BQCA, AC-42, and the VU series highlight the diversity of mechanisms and potential for precision treatment tailored to receptor expression profiles and schizophrenia endophenotypes [3]."

CNS Disorders • Psychiatry • Schizophrenia

Sigma-1 receptor agonists show neuroprotective and antidepressant effects: a translational review of clinical and preclinical evidence (ECNP 2025) - "Fluvoxamine—an SSRI with sigma-1 receptor agonism—demonstrated greater efficacy than paroxetine in randomized controlled trials for treatment-resistant depression, reducing MADRS scores by 12.8 vs. 8.3 points (p < 0.05, Cohen's d = 0.71). Sigma-1 receptor agonists represent a unique and promising therapeutic class that acts at the interface of neurodegeneration and neuropsychiatry. Their pleiotropic mechanisms—ranging from modulation of ER-mitochondrial signaling to neurotrophin upregulation—position them as ideal candidates for treating diseases with overlapping molecular substrates such as AD and MDD. As research advances, sigma-1-targeting drugs like Anavex 2-73 may pave the way toward disease-modifying treatments, offering both symptomatic relief and neuroprotection."

Preclinical • Review • Alzheimer's Disease • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • Aβ42

Anavex Life Sciences Announces Publication of Oral Blarcamesine Describing a New Class of Clinical Precision Medicine from Phase IIb/III Alzheimer’s Disease Trial (Anavex Press Release) - "'This publication of blarcamesine, a once-daily oral small molecule, is very exciting, with demonstrated superior clinical efficacy versus approved therapies and slowed neurodegeneration in early Alzheimer’s patients.'....'Coupled with a strong safety profile and no need for routine MRI monitoring, its unique mechanism of action supports a Precision Medicine approach—potentially benefiting up to 70% of early Alzheimer's disease patients by targeting genetically relevant populations.'"

P2/3 data • Alzheimer's Disease

Anavex Life Sciences Announces Oral Blarcamesine Cognitive Resilience Results Approximating Normal Aging in New Precision Medicine Clinical Data from Phase IIb/III Alzheimer’s Disease Trial (Anavex Press Release) - "In comparison, the respective placebo group in the ANAVEX2-73-AD-004 Phase IIb/III ABCLEAR3 population, ADAS-Cog13 LS mean declined by 5.592 points resulting in an ADAS-Cog13 LS mean difference of -4.739 [95% CI -7.370, -2.108]; P=0.0004. This represents a 84.7% reduction in decline at 48 weeks of blarcamesine treatment vs placebo on the cognitive endpoint ADAS-Cog13....Data confirmed that within a heterogeneous Alzheimer’s disease population by targeting a prevalent genetic profile through Precision Medicine approach, the efficacy of blarcamesine may be further improved."

P2/3 data • Alzheimer's Disease

Anavex Life Sciences Reports New Publication in Medical Journal Highlighting the Established Precise Autophagy Mechanism with Blarcamesine (GlobeNewswire) - "This new publication confirms with additional biochemical data in more detail the autophagy restoration mechanism of S1R activation with blarcamesine. The specific S1R-localized motif responsible for physiologically relevant interactions with autophagy proteins—promoting autophagosome biogenesis, autophagic cargo reception, and lysosome fusion—was confirmed and modulated by blarcamesine."

Preclinical • Alzheimer's Disease

Anavex Life Sciences Announces Positive Precision Medicine Results from up to 4-Years of Oral Blarcamesine Treatment in Phase IIb/III Open-Label Extension Trial in Early Alzheimer’s Disease (Anavex Press Release) - P2b/3 | N=300 | ATTENTION-AD (NCT04314934) | Sponsor: Anavex Life Sciences Corp. | "The data were presented...at the 2025 Alzheimer's Association International Conference (AAIC)...Blarcamesine-treated patients continue to accrue benefit through up to 4 years, as measured by the pre-specified clinical endpoints ADAS-Cog13 and ADCS-ADL, respectively. In the intent-to-treat (ITT) population, delayed-start analysis of treatment with oral blarcamesine was significant for both cognition and function, reflecting the importance of early treatment initiation. For ADAS-Cog13 a significant difference between the early-start and late-start treatment groups at Week 192 (LS mean difference −3.83, P = 0.0165) was observed....While in the ITT population trial participants showed significant improvement versus placebo after 48 Weeks in the ANAVEX2-73-AD-004 double-blind (DB) clinical trial by 36.3% for the key endpoints, ADAS-Cog13 and 27.6% for CDR-SB, respectively..."

P2/3 data • Alzheimer's Disease

Anavex Life Sciences Announces New Publication in Medical Journal: Blarcamesine Prevented Cognitive Impairment in Animal Model of Alzheimer’s Disease (GlobeNewswire) - "This study shows that a pre-treatment with blarcamesine prevented Amyloid beta-induced memory impairment and brain oxidative injury suggesting that blarcamesine is an attractive candidate for Alzheimer's disease pharmacological prevention...While placebo-controlled mice developed significant amyloid toxicity in the brains after the toxic Aβ25-35 peptide injection, in animals pre-treated with blarcamesine, significant protection was observed with less vulnerability to Aβ_25-35-induced oxidative stress and less vulnerability to develop learning and memory deficits."

Preclinical • Alzheimer's Disease

Prevention of memory impairment and hippocampal injury with blarcamesine in an Alzheimer's disease model. (PubMed, Neurosci Lett) - "We observed significant preventions of Aβ25-35-induced memory impairments, for both spatial working and contextual long-term memories, and of Aβ25-35-induced increase in lipid peroxidation in the mouse hippocampi. These new insights, together with blarcamesine's clinical record in early AD render blarcamesine an attractive candidate for AD pharmacological prevention."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Dementia

Anavex Life Sciences Announces Positive up to 4-Years Oral Blarcamesine Results from Phase IIb/III Open-Label Extension Trial in Early Alzheimer’s Disease (GlobeNewswire) - P2b/3 | N=300 | ATTENTION-AD (NCT04314934) | Sponsor: Anavex Life Sciences Corp. | "ATTENTION-AD (ANAVEX 2-73-AD-EP-004) trial result was presented at the AD/PD 2025 Conference...The delayed-start analysis for ADAS-Cog13 showed a significant difference between early start and late start treatment groups up to Week 192 (LS mean difference -3.83, P = 0.0165), favoring the early start group. Together these results suggest that participants who initiated treatment with blarcamesine earlier in their disease progression showed greater stability of cognitive function compared to those who did not initiate blarcamesine until ~1 year later...In addition, to place these findings in context, an ADAS-Cog13 score difference between the treatment groups at Week 192 being larger than 2 points is considered a clinically meaningful improvement...Similarly, the delayed-start analysis for ADCS-ADL showed numerically favorable results for the early start group over the late start group..."

P2/3 data • Alzheimer's Disease

Anavex Life Sciences Announces Presentation at 9th International Conference on Alzheimer’s Disease and Related Disorders in the Middle East (GlobeNewswire) - "Anavex Life Sciences Corp...today announced that Marwan Noel Sabbagh, MD, Professor of Neurology at Barrow Neurological Institute and Chairman of Anavex’s Scientific Advisory Board gave an oral presentation titled, 'Oral Blarcamesine Novel Mechanism for Alzheimer Disease: Autophagy Restoration through Upstream SIGMAR1 Activation Clinical Efficacy Phase IIb/III Trial' at the 9th International Conference on Alzheimer’s Disease and Related Disorders in the Middle East."

P2/3 data • Alzheimer's Disease

Concerns about Anavex's clinical trial of Blarcamesine. (PubMed, J Prev Alzheimers Dis) - No abstract available

Journal

PHASE IIB/III ATTENTION-AD STUDY: OVER THREE YEARS OF CONTINUOUS TREATMENT WITH ORAL BLARCAMESINE CONTINUES TO SIGNIFICANTLY BENEFIT EARLY ALZHEIMER'S DISEASE PATIENTS (ADPD 2025) - "The Results provide further support for the efficacy Results in the pivotal phase IIb/III study. No new safety findings have been observed with continued blarcamesine treatment over three years with good comparative safety profile and no associated neuroimaging adverse events."

Clinical • P2/3 data • P2b data • Alzheimer's Disease • CNS Disorders

Anavex Life Sciences Announces Issuance of Blarcamesine (ANAVEX 2-73) Composition of Matter U.S. Patent Expanding its Intellectual Property Portfolio (GlobeNewswire) - "Anavex Life Sciences Corp...announced today it was issued a new U.S. Patent No. 12,180,174 entitled 'A2-73 CRYSTALLINE POLYMORPH COMPOSITIONS OF MATTER AND METHODS OF USE THEREOF' from the United States Patent and Trademark Office (USPTO) for its U.S. Patent Application Serial Number USSN: 17/978,818. This new patent claims crystalline forms of the dihydrogen phosphate salt of ANAVEX 2-73 (blarcamesine), freebase, transdermal patches and enteric coated oral dosage forms including the same for neuroprotection and treatment of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and other disorders."

Patent • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Anavex Life Sciences Announces Peer-Reviewed Publication of Oral Blarcamesine Phase IIb/III Data in The Journal of Prevention of Alzheimer’s Disease (GlobeNewswire) - P2b/3 | N=300 | ATTENTION-AD (NCT04314934) | Sponsor: Anavex Life Sciences Corp. | "Anavex Life Sciences Corp...today announced that The Journal of Prevention of Alzheimer’s Disease (JPAD) has published peer-reviewed detailed results from the Phase IIb/III study evaluating oral blarcamesine (ANAVEX2-73) for the treatment of early Alzheimer’s Disease (AD). Once daily oral blarcamesine, demonstrating a safety profile with no associated neuroimaging adverse events, significantly slowed clinical progression by 36.3% at 48 weeks with blarcamesine group as well as the prespecified SIGMAR1 wild-type gene group by 49.8% at 48 weeks on the prespecified primary cognitive endpoint ADAS-Cog13...Data from the Phase IIb/III trial demonstrated oral once daily blarcamesine pre-specified clinical efficacy through upstream SIGMAR1 activation."

P2/3 data • Alzheimer's Disease

New Phase IIb/III Clinical Data Demonstrates Over Three Years of Continuous Treatment with Oral Blarcamesine to Significantly Benefit Early Alzheimer’s Disease Patients (GlobeNewswire) - P2/3 | N=300 | ATTENTION-AD (NCT04314934) | Sponsor: Anavex Life Sciences Corp. | "The delayed-start analysis for ADAS-Cog13 showed a significant difference between early start and late start treatment groups at Week 144 (LS mean difference -2.70, P = 0.0348), favoring the early start group. This observed treatment difference continued to increase up to Week 192 (LS mean difference -3.83, P = 0.0165)...The delayed-start analysis for ADAS-Cog13 showed a significant difference between early start and late start treatment groups at Week 144...favoring the early start group. This observed treatment difference continued to increase up to Week 192 (LS mean difference -3.83, P = 0.0165)...Blarcamesine exhibited a favorable safety profile with the majority of adverse events (AEs) mild to moderate in severity (Grade 1 or 2), were predominantly linked to the initial titration phase, and could be managed with adjusted titration schedules...There were no deaths related to blarcamesine."

P2/3 data • Alzheimer's Disease

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial. (PubMed, J Prev Alzheimers Dis) - P2/3 | "Blarcamesine, demonstrating a safety profile with no associated neuroimaging adverse events, significantly slowed clinical progression by 36.3% at 48 weeks with blarcamesine group as well as the individual 30 mg (by 34.6%) and 50 mg (by 38.5%) blarcamesine groups vs. placebo on the prespecified primary cognitive endpoint ADAS-Cog13. The prespecified secondary endpoint CDR-SB, which is used as the sole primary endpoint in recent successful AD drug submissions, is significantly improved at Week 48 with blarcamesine relative to placebo. The findings are supported by biomarkers from the A/T/N spectrum, including plasma Aβ42/40-ratio and reduction of whole brain atrophy. Additionally, the prespecified SIGMAR1 gene variant subgroup analysis confirmed beneficial clinical effect of blarcamesine group through upstream SIGMAR1 activation - subjects with the common SIGMAR1 wild-type gene (excluding carriers of the mutated SIGMAR1 rs1800866 variant) experienced an even..."

Clinical • Journal • P2/3 data • P2b data • Alzheimer's Disease • CNS Disorders • Aβ42 • SIGMAR1