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

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

Drug Development. (PubMed, Alzheimers Dement) - "In this phase 2b/3 randomized clinical trial, we found that among participants with early AD, blarcamesine significantly slowed clinical progression on prespecified primary outcome global and cognitive measures at 48 weeks in the ITT population. These results suggest that blarcamesine may be an effective, safe, and novel scalable oral treatment for early AD."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Blarcamesine Receives EMA Filing Acceptance for Treatment of Alzheimer’s Disease (GlobeNewswire) - "Anavex Life Sciences Corp...today announced that the European Medicines Agency (EMA) has accepted for review the Marketing Authorization Application (MAA) for blarcamesine (ANAVEX2-73), an investigational drug for the treatment of Alzheimer’s disease. The Company is looking forward to working with the EMA...The MAA is supported by data from the randomized, double-blind, placebo-controlled Phase IIb/III, ANAVEX2-73-AD-004 trial and it’s up to 144 week open-label-extension (OLE) ATTENTION-AD ANAVEX2-73-AD-EP-004 trial investigating blarcamesine in early Alzheimer’s disease."

EMA filing • Alzheimer's Disease • CNS Disorders

Anavex Life Sciences to Report New Long-Term Oral Blarcamesine Phase IIb/III Alzheimer’s Disease Data at J.P. Morgan 2025 Healthcare Conference (GlobeNewswire) - "Anavex Life Sciences Corp...today announced its upcoming presentation of topline long-term data from the Phase IIb/III ATTENTION-AD Open-Label-Extension (OLE) trial at the J.P. Morgan 2025 Healthcare Conference, taking place January 13–16, 2025, in San Francisco, CA...The presentation will highlight new findings from the ATTENTION-AD study evaluating potential benefit of oral once daily blarcamesine (ANAVEX2-73) in early Alzheimer’s disease. The data reflect up to 144 weeks of continuous treatment in the OLE phase, following the prior 48-week double-blind Phase IIb/III study, for a total of up to 192 weeks (~4 years) of safety and efficacy data."

P2/3 data • Alzheimer's Disease

Anavex Life Sciences Announces Submission of Blarcamesine MAA for Treatment of Alzheimer’s Disease to EMA (GlobeNewswire) - "Anavex Life Sciences Corp...today announced the submission of the blarcamesine (ANAVEX2-73) MAA (Marketing Authorization Application) to the European Medicines Agency (EMA). The MAA submission is for the treatment of Alzheimer’s Disease."

EMA filing • Alzheimer's Disease • CNS Disorders

Anavex Life Sciences Announces Acceptance of Peer-Reviewed Manuscript of Oral Blarcamesine Phase IIb/III Data in a Reference Alzheimer’s Disease Journal (GlobeNewswire) - "Anavex Life Sciences Corp...today announced the acceptance of a peer-reviewed manuscript titled, 'Blarcamesine for the treatment of Early Alzheimer’s Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial,' in a medical journal with focus on Alzheimer’s disease. The publication date is expected around Q4 2024/Q1 2025...'We are on track for regulatory submission of oral blarcamesine in Europe (EMA) in the current quarter 2024.'"

EMA filing • P2/3 data • Alzheimer's Disease • CNS Disorders

Anavex’s Blarcamesine Achieves Pre-specified Efficacy in Phase IIb/III Alzheimer’s Trial: Data Presented at CTAD Conference 2024 (GlobeNewswire) - P2/3 | N=509 | NCT03790709 | Sponsor: Anavex Life Sciences Corp. | "Clinical data confirmed the mechanism of action (MoA) by pre-specified SIGMAR1 gene analysis in people with early Alzheimer's disease (AD)..This was confirmed in the Phase IIb/III study analysis: Over 48 weeks, blarcamesine significantly slowed clinical progression by 36.3% in the primary endpoint ADAS-Cog13 [LS mean ADAS-Cog13 difference of -2.027; P=0.008] in the ITT analysis. This signal was even stronger in the pre-specified common SIGMAR1 wild type (WT) group with slowed clinical progression by 49.8% at 48 weeks in the active group vs. placebo, respectively [LS mean ADAS-Cog13 difference of -2.317; P=0.015]. Equal analysis with CDR-SB led to comparable consistent results...'We are on track for regulatory submission of blarcamesine in Europe (EMA) in the current quarter 2024.'"

EMA filing • P2/3 data • Alzheimer's Disease • CNS Disorders

Phase IIb/III Trial of Blarcamesine in Early Alzheimer Disease Demonstrates Pre-specified Clinical Efficacy Through Upstream SIGMAR1 Activation (CTAD 2024) - No abstract available

Clinical • Late-breaking abstract • P2/3 data • P2b data • Alzheimer's Disease • CNS Disorders

Pre-specified SIGMAR1 Gene Variant Analysis in Phase IIb/III Trial Supports Precision Medicine Mechanism of Action (MoA) with Improved Treatment Effect of Blarcamesine in Early Alzheimer Disease (CTAD 2024) - No abstract available

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

Rett Syndrome: The Emerging Landscape of Treatment Strategies. (PubMed, CNS Drugs) - "While some of these have been unrewarding such as sarizotan, others have been quite promising including the approval of trofinetide by the FDA in 2023 as the first agent available for specific treatment of RTT. Blarcamesine has been trialed in phase 3 trials, 14 agents have been studied in phase 2 trials, and 7 agents are being evaluated in preclinical/translational studies...Taken together, progress in understanding and treating RTT over the past 40 years has been remarkable. This suggests that further advances can be expected."

Journal • Review • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Mood Disorders • Movement Disorders • Orthopedics • Parkinson's Disease • Psychiatry • Rare Diseases

ATTENTION-AD: OLE of Phase 2b/3 Study ANAVEX2-73-AD-004 (clinicaltrials.gov) - P2/3 | N=300 | Completed | Sponsor: Anavex Life Sciences Corp. | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2/3 | N=450 ➔ 300

Enrollment change • Phase classification • Trial completion • Alzheimer's Disease • CNS Disorders

Anavex Life Sciences Reports Fiscal 2024 Third Quarter Financial Results and Provides Business Update - "Completed last patient last visit in the ATTENTION-AD open-label extension 96-week trial. Interim data expected in the second half of 2024...Initiation of ANAVEX 2-73 Phase 2b/3 >6-month trial, including biomarkers, which we believe may be key to understanding drug effects on Parkinson’s disease pathophysiology and account for the recently changing context in the field of Parkinson’s disease is expected in the second half of 2024."

New P2/3 trial • P2/3 data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Results from Anavex Life Sciences Landmark Phase IIb/III Trial of Blarcamesine Presented at Alzheimer's Association Conference (GlobeNewswire) - P2/3 | N=509 | NCT03790709 | Sponsor: Anavex Life Sciences Corp. | "Anavex Life Sciences...presented comprehensive results from the Phase IIb/III study showing that blarcamesine (ANAVEX 2-73), once daily orally, significantly slowed clinical decline in people with early Alzheimer's disease (AD)....Blarcamesine significantly slowed clinical progression by 38.5% and 34.6% at 48 weeks in 50 mg and 30 mg groups vs. placebo, respectively, on the prespecified primary cognitive endpoint ADAS-Cog13....The functional co-primary endpoint, ADCS-ADL, was trending positive but did not reach significance at Week 48. A possible explanation is that the ADCS-ADL scale is designed for AD with overt dementia and is less sensitive for early AD.2 The prespecified key secondary composite endpoint CDR-SB...is significant at both 30 mg and 50 mg at Week 48....'Full regulatory submission of blarcamesine in Europe (EMA) is expected in Q4 2024'."

EMA filing • P2/3 data • Alzheimer's Disease

Central role of Sigma-1 receptor in ochratoxin A-induced ferroptosis. (PubMed, Arch Toxicol) - "In this investigation, cell viability, malondialdehyde (MDA) levels, glutathione (GSH) levels, and protein expressions in HK-2 cells treated with OTA and/or Ferrostatin-1/blarcamesine hydrochloride/BD1063 dihydrochloride were assessed. The results indicate that a 24 h-treatment with 1 μM OTA significantly induces ferroptosis by inhibiting Sig-1R, subsequently promoting nuclear receptor coactivator 4 (NCOA4), long-chain fatty acid-CoA ligase 4 (ACSL4), arachidonate 5-lipoxygenase (ALOX5), autophagy protein 5 (ATG5), and ATG7, inhibiting ferritin heavy chain (FTH1), solute carrier family 7 member 11 (SLC7A11/xCT), glutathione peroxidase 4 (GPX4), peroxiredoxin 6 (PRDX6), and ferroptosis suppressor protein 1 (FSP1), reducing GSH levels, and increasing MDA levels (P < 0.05). In conclusion, OTA induces ferroptosis by inhibiting Sig-1R, subsequently promoting ferritinophagy, inhibiting GPX4/FSP1 antioxidant systems, reducing GSH levels, and ultimately increasing..."

Journal • ACSL4 • AIFM2 • ATG7 • GPX4 • NCOA4 • PRDX6 • SLC7A11

Blarcamesine in Early Alzheimer Disease Phase 2b/3 Randomized Clinical Trial (AAIC 2024) - "In this phase 2b/3 randomized clinical trial, we found that among participants with early AD, blarcamesine significantly slowed clinical progression on prespecified primary outcome global and cognitive measures at 48 weeks in the ITT population. These results suggest that blarcamesine may be an effective, safe, and novel scalable oral treatment for early AD."

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

Sigma Receptor Ligands Are Potent Antiprion Compounds that Act Independently of Sigma Receptor Binding. (PubMed, ACS Chem Neurosci) - "While the precise details of the mechanism of action of these molecules remain to be determined, the present work forms the basis for further investigation of these compounds in preclinical studies. Given the therapeutic utility of several of the tested compounds, including rimcazole and haloperidol for neuropsychiatric conditions, (+)-pentazocine for neuropathic pain, and the ongoing clinical trials of SA 4503 and ANAVEX2-73 for ischemic stroke and Alzheimer's disease, respectively, this work has immediate implications for the treatment of human prion disease."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Ischemic stroke • Mental Retardation • Neuralgia • Oncology • Pain • Psychiatry

The involvement of SigmaR1K142 degradation mediated by ERAD in neural senescence linked with CdCl2 exposure. (PubMed, J Hazard Mater) - "In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2-73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice...CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Metabolic Disorders • Targeted Protein Degradation • NOTCH1

BLARCAMESINE IN EARLY SYMPTOMATIC ALZHEIMER DISEASE PHASE 2B/3 RANDOMIZED CLINICAL TRIAL (ADPD 2024) - P2b | "Among participants with early symptomatic AD, blarcamesine was generally safe, well tolerated and significantly slowed clinical progression at 48 weeks, which is also corroborated by biomarkers from the A/T/N spectrum, including plasma Aβ42/40 ratio increase and reduction of brain atrophy in several key regions of the brain measured by MRI. ClinicalTrials.gov Identifier: NCT03790709."

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

Anavex Life Sciences Announces Grant of U.S. Patent Covering Blarcamesine (ANAVEX 2-73) for Treatment of Neurodevelopmental Disorders (GlobeNewswire) - "Anavex Life Sciences Corp...announced today it was granted new U.S. Patent No. 11,839,600...from the United States Patent and Trademark Office (USPTO) for its patent application number 17/890,083. Anavex’s newest patent expands coverage of ANAVEX 2-73 (blarcamesine) therapy to ameliorate various conditions associated with loss-of-function mutations of the gene encoding methyl-CpG binding protein (MeCP2). The patent claims protect use of ANAVEX 2-73 (blarcamesine) to address a range of symptoms exhibited by patients suffering from neurodevelopmental and neurological conditions related to McCP2..."

Patent • CNS Disorders • Developmental Disorders