ANAVEX2-73-RS-003 is a Phase 2/3, double-blind, randomized, placebo-controlled dose escalation safety, tolerability and efficacy study in patients 5-17 years of age with RTT using endpoints including multiple clinical and exploratory molecular and biochemical measures.

Start Date01 Jul 2020

Sponsor / Collaborator

Anavex Life Sciences Corp.

[+2]

NCT04314934

/ CompletedPhase 2/3

Open Label Extension Study for Patients With Early Alzheimer's Disease (AD) Enrolled in Study ANAVEX2-73-AD-004

This is a Phase 2b/3 open-label extension study to evaluate the effects of ANAVEX2-73 on safety and effficacy of daily treatment.

Start Date10 Oct 2019

Sponsor / Collaborator

Anavex Life Sciences Corp.

[+2]

NCT04575259

/ CompletedPhase 2

Open Label Extension Study for Patients With Parkinson's Disease With Dementia Enrolled in Study ANAVEX2-73-PDD-001

This is a Phase 2 open-label extension study to evaluate the effects of ANAVEX2-73 on safety and efficacy of daily treatment.

Start Date10 Oct 2019

Sponsor / Collaborator

Anavex Life Sciences Corp.

[+2]

100 Clinical Results associated with Blarcamesine

100 Translational Medicine associated with Blarcamesine

100 Patents (Medical) associated with Blarcamesine

Literatures (Medical) associated with Blarcamesine

01 Jan 2025·JPAD-Journal of Prevention of Alzheimers Disease

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial

Article

Author: Brodtmann, Amy ; Frank, Andrew ; Tartaglia, Carmela ; Woodward, Michael ; Mannering, Nicholas ; Pearson, Stephen ; Krishna, Vivek ; Smith, Eric ; Jin, Kun ; Grunfeld, Jennifer ; Grimmer, Timo ; O'Brien, Terence J ; MacSweeney, J Emer ; Asher, Aliya ; Brew, Bruce J ; Peters, Oliver ; Kurrle, Susan ; Evans, Craig ; Bharadwaj, Sneha ; Thompson, Alex ; Cohen, Sharon ; Tucker, Amanda ; Lewis, Simon J G ; Connell, Sandra ; Missling, Christopher U ; Frölich, Lutz ; Henri-Bhargava, Alexandre ; Hsiung, Ging-Yuek Robin ; Munisamy, Malathy ; Dautzenberg, Paul Lj ; Brittain, Rodney ; Bhatt, Neel ; Villa, Luca M ; Sharif, Saif ; Chertkow, Howard ; Perry, Richard ; Prins, Niels ; Lynch, Jennifer ; Macfarlane, Stephen ; Gordon, Elizabeth ; Sabbagh, Marwan N ; Short, Cathy ; Kaufmann, Walter E ; Kalafatis, Chris ; Oschmann, Patrick ; Pasternak, Stephen ; Mander, Alastair ; Rutgers, Sterre Malou ; Ingram, Jennifer ; Guizard, Nicolas ; Teo, Ken ; Lai, Rosalyn ; Wiltfang, Jens ; Chezem, William R ; Barton, David ; Jubault, Thomas ; Drysdale, Peter ; Sturm, Jonathan ; Morris, Philip ; Tacik, Pawel

BACKGROUND:

There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

OBJECTIVES:

The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

DESIGN:

ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

SETTING:

Multicenter - 52 medical research centers/hospitals in 5 countries.

INTERVENTION:

508 participants with early AD (Stage 3) were randomized to receive either blarcamesine (n = 338) in medium dose group 30 mg or in high dose group 50 mg or placebo (n = 170) oral capsules once daily for 48 weeks. Participants in these groups were offered to enroll into the open-label-extension study ATTENTION-AD, which completed June 2024, ClinicalTrials.gov Identifier NCT04314934.

MEASUREMENTS:

The co-primary cognitive and functional outcomes were assessed as change in ADAS-Cog13 and ADCS-ADL from baseline to 48 weeks. The outcomes include the secondary outcome CDR-SB and biomarkers from the A/T/N spectrum, plasma Aβ42/40-ratio and global brain volume changes measured by MRI. All clinical endpoints were analyzed using mixed model for repeated measures (MMRM), plasma biomarker measurements were analyzed by Welch's t-test, and volumetric MRI scans were analyzed by general linear model.

RESULTS:

Among 462 randomized participants in the intent-to-treat population (mean age, 73.7 years; 225 [48.7%] women), 338 (73.2%) completed the trial. The co-primary outcome was met under the multiplicity control rule, since the differences in the least-squares mean (LSM) change from baseline to 48 weeks between the prespecified blarcamesine and placebo groups for ADAS-Cog13 was significant at a level of P < 0.025 and for CDR-SB was significant at a level of P < 0.025, while ADCS-ADL did not reach significance at Week 48 (ADAS-Cog13 difference of -2.027 [95% CI -3.522 to -0.533]; P = 0.008; CDR-SB difference of -0.483 [95% CI -0.853 to -0.114]; P = 0.010; ADCS-ADL difference of 0.775 [95%CI -0.874 to 2.423]; P = 0.357). Plasma Aβ42/40-ratio increased significantly with blarcamesine group vs. placebo, (P = 0.048) and whole brain volume loss was significantly decreased (P = 0.002). Participants in the full safety population with ≥1 serious treatment-emergent adverse events (TEAEs) occurred in 56 participants (16.7%) in the blarcamesine and 17 (10.1%) in the placebo group. Common TEAEs included dizziness, which was transient and mostly mild to moderate in severity. One death in the blarcamesine group and 1 in the placebo group were both not considered treatment related.

CONCLUSIONS:

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 greater significant clinical benefit with slowed clinical progression by 49.8% at 48 weeks on the prespecified primary cognitive endpoint ADAS-Cog13. Oral once daily blarcamesine could represent a novel treatment in early AD and be complementary or alternative to anti-beta amyloid drugs.

01 Nov 2024·CNS DRUGS

Rett Syndrome: The Emerging Landscape of Treatment Strategies

Review

Author: Neul, Jeffrey L. ; Percy, Alan K ; Percy, Alan K. ; Neul, Jeffrey L ; Ananth, Amitha

Rett syndrome (RTT) has enjoyed remarkable progress in achieving specific therapies. RTT, a unique neurodevelopmental disorder first described in 1966, progressed slowly until the landmark paper of Hagberg and colleagues in 1983. Thereafter, rapid advances were achieved including the development of specific diagnostic criteria and the active search for a genetic etiology, resulting 16 years later in identification of variants in the methyl-CpG-binding protein (MECP2) gene located at Xq28. Shortly thereafter, the NIH Office of Rare Diseases funded the RTT Natural History Study (NHS) in 2003, initiating the acquisition of natural history data on clinical features from a large population of individuals with RTT. This information was essential for advancement of clinical trials to provide specific therapies for this disorder. In the process, the International Rett Syndrome Association (IRSA) was formed (now the International Rett Syndrome Foundation-IRSF), which participated directly in encouraging and expanding enrollment in the NHS and, subsequently, in developing the SCOUT program to facilitate testing of potential therapeutic agents in a mouse model of RTT. The overall objective was to review clinical characteristics developed from the NHS and to discuss the status of specific therapies for this progressive neurodevelopmental disorder. The NHS study provided critical information on RTT: growth, anthropometrics, longevity, key comorbidities including epilepsy, breath abnormalities, gastroesophageal dysfunction, scoliosis and other orthopedic issues, puberty, behavior and anxiety, and progressive motor deterioration including the appearance of parkinsonian features. Phenotype-genotype correlations were noted including the role of X chromosome inactivation. Development of clinical severity and quality of life measures also proved critical for subsequent clinical trials. Further, development of biochemical and neurophysiologic biomarkers offered further endpoints for clinical trials. Initial clinical trials prior to the NHS were ineffective, but advances resulting from the NHS and other studies worldwide promoted significant interest from pharmaceutical firms resulting in several clinical trials. 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. A landmark study in 2007 by Guy et al. demonstrated that activation of a normal MECP2 gene in a null mouse model resulted in significant improvement. Gene replacement therapy has advanced through translational studies to two current phase 1/2 clinical trials (Taysha102 and Neurogene-401). Additional genetic therapies are also under study including gene editing, RNA editing, and X-chromosome reactivation. Taken together, progress in understanding and treating RTT over the past 40 years has been remarkable. This suggests that further advances can be expected.

01 Oct 2024·ARCHIVES OF TOXICOLOGY

Central role of Sigma-1 receptor in ochratoxin A-induced ferroptosis

Article

Author: Liu, Shuangchao ; Han, Lingyun ; Chen, Wenying ; Zhou, Yao ; Deng, Huiqiong ; Wang, Hongwei ; Yang, Ruiran ; Shen, Xiao Li ; Yao, Song

Ochratoxin A (OTA), a secondary fungal metabolite known for its nephrotoxic effects, is prevalent in various feeds and food items. Our recent study suggests that OTA-induced nephrotoxicity is linked to the Sigma-1 receptor (Sig-1R)-mediated mitochondrial pathway apoptosis in human proximal tubule epithelial-originated kidney-2 (HK-2) cells. However, the contribution of Sig-1R to OTA-induced nephrotoxicity involving other forms of regulated cell death, such as ferroptosis, remains unexplored. 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 lipid peroxidation levels in vitro.

News (Medical) associated with Blarcamesine

12 Feb 2025

·www.anavex.com

Anavex Life Sciences Reports Fiscal 2025 First Quarter Financial Results and Provides Business Update

Company to host a webcast today at 8:30 a.m. Eastern Time NEW YORK – February 12, 2025 Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company focused on developing innovative treatments for Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) diseases, today reported financial results for its first quarter of fiscal 2025. “We are receiving growing support from stakeholders for the potential to advance a novel treatment for early Alzheimer’s disease with convenient oral dosing with potential clinical meaningful benefit,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “We are excited to potentially making a difference for individuals suffering from Alzheimer’s disease, by presenting a scalable treatment alternative alongside the ease of oral administration.” Recent Highlights: On January 27, 2025, Anavex announced it was issued a new composition of matter U.S. Patent, expected to remain in force at least until July 2039, entitled “A2-73 CRYSTALLINE POLYMORPH COMPOSITIONS OF MATTER AND METHODS OF USE THEREOF” from the United States Patent and Trademark Office (USPTO). 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. On January 15, 2025, Anavex announced that The Journal of Prevention of Alzheimer’s Disease (JPAD)  published peer-reviewed detailed results from the Phase IIb/III study evaluating oral blarcamesine (ANAVEX®2-73) 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, respectively. On January 13, 2025, Anavex provided topline long-term data from the Phase IIb/III ATTENTION-AD Open-Label-Extension (OLE) trial. The data demonstrated that over three years of continuous treatment with blarcamesine (ANAVEX®2-73) significantly reduced clinical decline showing continued clinically and meaningful benefit for early Alzheimer’s disease patients. On January 27, 2025, Anavex announced it was issued a new composition of matter U.S. Patent, expected to remain in force at least until July 2039, entitled “A2-73 CRYSTALLINE POLYMORPH COMPOSITIONS OF MATTER AND METHODS OF USE THEREOF” from the United States Patent and Trademark Office (USPTO). 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. On January 15, 2025, Anavex announced that The Journal of Prevention of Alzheimer’s Disease (JPAD)  published peer-reviewed detailed results from the Phase IIb/III study evaluating oral blarcamesine (ANAVEX®2-73) 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, respectively. On January 13, 2025, Anavex provided topline long-term data from the Phase IIb/III ATTENTION-AD Open-Label-Extension (OLE) trial. The data demonstrated that over three years of continuous treatment with blarcamesine (ANAVEX®2-73) significantly reduced clinical decline showing continued clinically and meaningful benefit for early Alzheimer’s disease patients. Financial Highlights: Cash and cash equivalents of $120.8 million at December 31, 2024 compared to $132.2 million at September 30, 2024. As of quarter end, the Company anticipates at current cash utilization rates and ranges, a runway of approximately 4 years. General and administrative expenses for the first quarter of $3.1 million compared to $2.7 million for the comparable first quarter of fiscal 2024. Research and development expenses for the first quarter of $10.4 million compared to $8.7 million for the comparable first quarter of fiscal 2024. Net loss for the first quarter of $12.1 million, or $0.14 per share, compared to a net loss of $8.6 million, or $0.11 per share for the comparable first quarter of fiscal 2024. Cash and cash equivalents of $120.8 million at December 31, 2024 compared to $132.2 million at September 30, 2024. As of quarter end, the Company anticipates at current cash utilization rates and ranges, a runway of approximately 4 years. General and administrative expenses for the first quarter of $3.1 million compared to $2.7 million for the comparable first quarter of fiscal 2024. Research and development expenses for the first quarter of $10.4 million compared to $8.7 million for the comparable first quarter of fiscal 2024. Net loss for the first quarter of $12.1 million, or $0.14 per share, compared to a net loss of $8.6 million, or $0.11 per share for the comparable first quarter of fiscal 2024. The financial information for the quarter ended December 31, 2024, should be read in conjunction with the Company’s consolidated financial statements, which will appear on EDGAR, www.sec.gov and will be available on the Anavex website at www.anavex.com. About Anavex Life Sciences Corp. Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn. Forward-Looking Statements Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks set forth in the Company’s most recent Annual Report on Form 10-K filed with the SEC. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. For Further Information: Anavex Life Sciences Corp. Research & Business Development Toll-free: 1-844-689-3939 Email: info@anavex.com Investors: Andrew J. Barwicki Investor Relations Tel: 516-662-9461 Email: andrew@barwicki.com

Clinical ResultPhase 3Financial StatementPhase 2

01 Feb 2025

·www.globenewswire.com

Anavex Life Sciences Announces Issuance of Blarcamesine (ANAVEX®2-73) Composition of Matter U.S. Patent Expanding its Intellectual Property Portfolio

Jan. 27, 2025 -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company focused on developing innovative treatments for Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) disorders, 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. Anavex’s newest patent will be expected to remain in force at least until July 2039, not including any patent term extensions. It will expand and supplement the current ANAVEX®2-73 (blarcamesine) patent portfolio, which includes several U.S. Patents, including U.S. Patent Nos. 10,413,519; 10,966,952; 11,661,405; and 11,498,908. “The issuance of this U.S. Patent again showcases our expertise in identifying and pursuing novel therapeutic forms and formulations that are rooted in science,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. He further added: “We believe the unique properties of the dihydrogen phosphate crystals make it possible in addition to convenient once daily oral dosing to also deliver the active (ANAVEX®2-73 freebase) in transdermal patches, which could simplify further the administration and boost patients’ compliance. As such, we believe that the addition of the dihydrogen phosphate crystals to our platform could greatly benefit the patients at large.” Crystal polymorphism is a unique phenomenon related to chiral compounds, wherein the compounds may crystallize into different crystal structures or crystal forms under different conditions and/or processes. Specifically for pharmaceuticals, polymorphic forms of drug substances ‘exist in different crystalline forms which differ in their physical properties’.1 These property differences may result in direct medical implications, such as ease of formulation, increased efficacy, and reduced side effects. For example, the widely used analgesic drug, acetaminophen has three polymorphic forms, I, II, and III, among which only Form I is made into commercial dosage forms as the other two forms are either meta-stable or unstable.2 Nonetheless, uncovering an optimal crystal form is NOT an easy or straightforward task, because there are so many variables and possibilities involved, and chance of success lies heavily on the researcher’s experience and insights into the compounds in question. Both ANAVEX®2-73 (blarcamesine) and ANAVEX®19-144 have the potential to form different crystal forms. Through its deep understanding and abundance experience with these two compounds, Anavex was successful in discovering crystal forms of ANAVEX®2-73 (blarcamesine) and ANAVEX®19-144 that have advantageous physiochemical and/or pharmacological properties. This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval. Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. 1 ICH HARMONISED TRIPARTITE GUIDELINE, SPECIFICATIONS: TEST PROCEDURES AND ACCEPTANCE CRITERIA FOR NEW DRUG SUBSTANCES AND NEW DRUG PRODUCTS: CHEMICAL SUBSTANCES Q6A, Current Step 4 version dated 6 October 1999, page 8. 2 Lee E.H., “A practical guide to pharmaceutical polymorph screening & selection,” Asian Journal of Pharmaceutical Sciences, Vol 9, Issue 4, August 2014, Pages 163-175. The content above comes from the network. if any infringement, please contact us to modify.

Clinical Result

17 Jan 2025

·www.globenewswire.com

Anavex Life Sciences Announces Peer-Reviewed Publication of Oral Blarcamesine Phase IIb/III Data in The Journal of Prevention of Alzheimer’s Disease

Blarcamesine potential novel oral treatment to target upstream Alzheimer’s disease pathology through autophagy enhancement Impairment of autophagy precedes both amyloid beta and tau tangles, and therefore anticipates the neurodegenerative process in Alzheimer’s disease Jan. 15, 2025 -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company focused on developing innovative treatments for Alzheimer's disease, Parkinson's disease, schizophrenia, neurodevelopmental, neurodegenerative, and rare diseases, including Rett syndrome, and other central nervous system (CNS) disorders, 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 (ANAVEX®2-73) 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. Oral once daily blarcamesine could represent a novel treatment in early Alzheimer’s disease and be complementary or alternative to injectable anti-beta amyloid drugs. “The Alzheimer’s disease community has been actively pursuing new medicines for decades. To have data like these published in JPAD gives us energy and hope. We are now seeing in the data what we suspected about blarcamesine for a long time – that it has the potential to make a clinical difference for people living with early Alzheimer’s disease,” said senior author behavioral neurologist Professor Dr. Marwan Noel Sabbagh MD, Chairman of the Scientific Advisory Board. “The advantage of blarcamesine lies in its small oral formulation, which offers clinical benefits for cognition and neurodegeneration. Its ease of administration and favorable safety profile make it an appealing option.” Data from the Phase IIb/III trial demonstrated oral once daily blarcamesine pre-specified clinical efficacy through upstream SIGMAR1 activation. SIGMAR1 is an integral membrane protein which activates an upstream compensatory process: Blarcamesine induces autophagy through SIGMAR1 activation resulting in restoring cellular homeostasis. “The results from the Phase IIb/III blarcamesine study show real promise for patients living with early Alzheimer’s disease,” said lead author Associate Professor Dr. Stephen Macfarlane, FRANZCP, Head of Clinical Services at the Dementia Centre, HammondCare and Principal Investigator. “Early Alzheimer’s disease can progress swiftly, and the potential for blarcamesine to target on a constitutional level of the pathology should bring hope and excitement to persons living with Alzheimer’s disease and those of us who care for them.” Impaired autophagy precedes both amyloid beta and tau tangles, and therefore anticipates the neurodegenerative process in Alzheimer’s disease.1 Hence, stabilization or restoration of autophagy can be seen as an early preventative measure countering the Alzheimer’s disease pathology. “Publication of the pivotal placebo-controlled Phase IIb/III blarcamesine early Alzheimer’s disease trial allows for a broader dissemination of these important data and highlights blarcamesine’s impressive and consistent clinical profile that has led to meaningful results for these patients,” said Juan Carlos Lopez-Talavera, MD, PhD, Head of Research and Development of Anavex. “These data serve as the foundation for the MAA filing that is currently being reviewed by the EMA. We are aiming to potentially advance an important medicine to patients in need.” Blarcamesine, a small molecule administered orally once daily, demonstrated clinically meaningful improvement over 48 weeks with primary endpoint ADAS-Cog13 score being larger than 2 points.2 This suggests superior numerical clinical efficacy compared to approved therapies while also slowing neurodegeneration in early Alzheimer’s disease patients. Blarcamesine’s safety profile indicates not requiring routine MRI monitoring, and given its differentiated mechanism of action, oral blarcamesine could represent a novel treatment that could be complementary or an alternative to injectable anti-beta amyloid monoclonal antibody drugs. “The peer-reviewed publication of these data underscores the significance of the findings for both the scientific community and those focused on Alzheimer's disease,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “Alzheimer's disease is a highly complex condition, and this dataset plays a crucial role in advancing our understanding of the Phase IIb/III results. We are grateful to the dedication from participants, their families, and the sites for taking part in this important study.” This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain health authority approval. The publication may be accessed here. There are an estimated 7 million people in Europe with Alzheimer’s disease, a number expected to double by 2030, according to the European Brain Council.3 The World Health Organization (WHO) estimated the cost in Europe of caring for people with dementia, including Alzheimer's disease, at $439 billion, or $31,144 per person in 2019. That includes hospital care, medicines, diagnostics, informal caregiver time, community services and long-term care facility costs.4,5 Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate designed to restore cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. __________________________ 1 Christ MG, Clement AM, Behl C. The Sigma-1 Receptor at the Crossroad of Proteostasis, Neurodegeneration, and Autophagy. Trends Neurosci. 2020 Feb;43(2):79-81; Chen, J., He, HJ., Ye, Q. et al. Defective Autophagy and Mitophagy in Alzheimer’s Disease: Mechanisms and Translational Implications. Mol Neurobiol 58, 5289–5302 (2021). 2 Muir RT, Hill MD, Black SE, Smith EE. Minimal clinically important difference in Alzheimer's disease: Rapid review. Alzheimers Dement. 2024;20(5):3352-3363. doi:10.1002/alz.13770 3 https://www.braincouncil.eu/projects/rethinking-alzheimers-disease/ 4 Jönsson L. The personal economic burden of dementia in Europe. Lancet Reg Health Eur. 2022 Jul 25;20:100472. doi: 10.1016/j.lanepe.2022.100472. PMID: 35910037; PMCID: PMC9326307. 5 World Health Organization (WHO); 2021. Global status report on the public health response to dementia. The content above comes from the network. if any infringement, please contact us to modify.

Clinical Result

100 Deals associated with Blarcamesine

External Link

KEGG	Wiki	ATC	Drug Bank
D11383	Blarcamesine	-	DB05592

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	NDA/BLA	EU	Anavex Life Sciences Corp.	20 Nov 2023
Rett Syndrome	Phase 3	AU	Anavex Life Sciences Corp.	06 May 2019
Rett Syndrome	Phase 3	GB	Anavex Life Sciences Corp.	06 May 2019
Fragile X Syndrome	Phase 3	US	Anavex Life Sciences Corp.	-
Dementia due to Parkinson's disease	Phase 2	AU	Anavex Life Sciences Corp.	09 Jul 2018
Dementia due to Parkinson's disease	Phase 2	ES	Anavex Life Sciences Corp.	09 Jul 2018
Parkinson Disease	Phase 2	AU	Anavex Life Sciences Corp.	09 Jul 2018
Parkinson Disease	Phase 2	ES	Anavex Life Sciences Corp.	09 Jul 2018
Angelman Syndrome	Phase 1	-	Anavex Life Sciences Corp.	-
Spasms, Infantile	Phase 1	-	Anavex Life Sciences Corp.	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04314934 (ATTENTION-AD, GlobeNewswire) Manual	Phase 2/3	Alzheimer Disease	-	blarcamesine (early start treatment)	xusqztyudx(pltssztybe) = from previously 25.2% in the ANAVEX®2-73-AD-004 trial to 9.6% in the ATTENTION-AD trial. nyqnhxhxen (fwteqydqkg ) View more	Positive	13 Jan 2025
				blarcamesine (late start treatment)
NCT04314934 (GlobeNewswire) Manual	Phase 2/3	Alzheimer Disease	-	Blarcamesine 50 mg	jppxnzhenh(vijdexovhp) = rocblxrqsh tizzqzjnjy (zlvlhccbnw ) View more	Positive	28 Jul 2024
				Blarcamesine 30 mg	jppxnzhenh(vijdexovhp) = ghsglfcmrg tizzqzjnjy (zlvlhccbnw ) View more
NCT04304482 (EXCELLENCE, GlobeNewswire) Manual	Phase 2/3	Rett Syndrome	92	ANAVEX2-73	hbmlcqosqr(kbmpppiggc) = veheghrjvr txrnbxmsky (qtpmfnnokw, 2.150) View more	Positive	02 Jan 2024
				Placebo	hbmlcqosqr(kbmpppiggc) = xrbwghicdj txrnbxmsky (qtpmfnnokw, 2.537) View more
NCT03790709 (Corporate Publications) Manual	Phase 2/3	Alzheimer Disease	508	ANAVEX2-73	njfbiwijri(upzttwsuwm): Difference = -1.783 (95% CI, −3.314 - −0.251), P-Value = 0.0226 Met View more	Positive	14 Sep 2023
				Placebo
NCT03790709 (ANAVEX2-73-AD-004, GlobeNewswire) Manual	Phase 2/3	Alzheimer Disease	509	Blarcamesine	vthkofbhkq(wneyjfbfao): OR = 1.84, P-Value = 0.015 View more	Positive	01 Dec 2022
				Placebo
NCT03758924 (Biospace) Manual	Phase 2	Rett Syndrome SIGMAR1	-	Blarcamesine	bgtknkhwuf(olnhujjnqk) = mxgnvyfvdt tjarnqevcw (etwygadgkm ) View more	Positive	21 Jun 2021
				Placebo	-
CTAD2015	Phase 2	-	-	ANAVEX 2-73	geaqoywlnj(elxjizpfjw) = The average Cogstate test improved across the test batteries owsgkxmkfn (pglvcqmces ) View more	Positive	04 Nov 2015

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