Long-Term Follow-Up to Evaluate the Safety of LX1001 in Participants With APOE4 Homozygote Alzheimer's Disease
The primary purpose of this long-term follow-up study is to assess the long-term safety profile of APOE4 homozygote participants who were administered gene therapy (LX1001) for the treatment of Alzheimer's disease in Study LX100101. A secondary objective is to assess the biomarker as shown by the conversion of CSF APOE isoforms from APOE4 to APOE2-APOE4. Additional secondary outcomes include amyloid PET scan, CSF markers (including Aβ42, Aβ42/Aβ40 ratio T--tau, and P-tau), and quantitative MRI (and other biomarkers that may be informative for this therapeutic approach). Other secondary objectives include instruments to assess cognitive and clinical AD and to evaluate if treatment with AAVrh.10hAPOE2 improves brain tau pathology with tau PET scan (LX1001-01 Cohort 3 only).
A 52-Week, Multicenter, Phase 1/2 Open-label Study to Evaluate the Safety of LX1001 in Participants With APOE4 Homozygote Alzheimer's Disease
This clinical trial is an open label, dose-ranging study designed to evaluate gene therapy to treat patients who are APOE4 homozygotes with clinical diagnosis varying from mild cognitive impairment due to Alzheimer's, mild dementia due to Alzheimer's disease, and moderate dementia due to Alzheimer's disease.
LAS VEGAS, Feb. 27, 2023 /PRNewswire/ --
The prevalence of Alzheimer's disease has been rising over the past few years, which prompts the growing demand for treatment options. The increasing prevalence of Alzheimer's disease and the growing research and development activities to develop novel therapies to treat Alzheimer's disease to drive the market. The companies developing the potential therapies in the last stage of development include Eli Lilly and Company, AB Sciences, AZTherapies, and several others.
Alzheimer's Disease Pipeline Insight – 2023
' report provides comprehensive global coverage of available, marketed, and pipeline Alzheimer's disease therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the Alzheimer's disease pipeline domain.
Key Takeaways from the Alzheimer's Disease Pipeline Report
DelveInsight's Alzheimer's disease pipeline report depicts a robust space with
150+ active players working to develop
160+ pipeline therapies for Alzheimer's disease treatment.
Key Alzheimer's disease companies such as
Biogen, AZTherapies, Cerecin, Neurotrope, Synaptogenix, INmune Bio, Cassava Sciences, EIP Pharma, Neuraly, AB Science, Cortexyme, Anavex Life Sciences, Athira Pharma, Time Therapeutics, Denali Therapeutics Inc., Alector Inc., Lexeo Therapeutics, TrueBinding, Inc., Vaccinex Inc., Annovis Bio Inc., Eisai Inc., Hoffmann-La Roche, Ionis Pharmaceuticals, Inc., Otsuka Pharmaceutical Co., Ltd., Cognition Therapeutics, Merck Sharp & Dohme LLC, ImmunoBrain Checkpoint, AbbVie, AriBio Co., Ltd., Oryzon Genomics S.A., Eli Lilly and Company, Neurokine Therapeutics, Excelsior, Seelos Therapeutics, Inc., Janssen Research & Development, LLC, Shanghai Hengrui Pharmaceutical Co., Ltd., reMYND, Alzinova AB, VTBIO Co. LTD, BioVie Inc., Prothena Corporation plc, Coya Therapeutics, Inc., and others are evaluating new Alzheimer's disease drugs to improve the treatment landscape.
Promising Alzheimer's disease pipeline therapies in various stages of development include
ALZT-OP1, Tricaprilin, Bryostatin-1, INB03, Sumifilam, Neflamapimod, Pegylated exenatide, NLY-02, Masitinib, Atuzaginstat, COR588, Blarcamesine, NDX-1017, Bromocriptine, DNL788, AL002, CMS121, LX1001, TB006, Pepinemab, Posiphen, E2814, RO7126209, IONIS MAPTRx, Brexpiprazole, CT1812, MK-1942, IBC Ab002, ABBV-916, AR1001, ORY-2001, LY3372689, MW150, EX039, SLS-005, Seltorexant, Donanemab, SHR-1707, REM0046127, ALZ-101, VT301, NE3107, PRX005, MK-6240, and others.
Lantheus Holdings, Inc. announced it had
Cerveau Technologies, Inc. ("Cerveau"). Cerveau's asset is
MK-6240, a second-generation F 18-labeled positron emission tomography ("PET") imaging agent that targets Tau tangles in Alzheimer's disease.Under the terms of the agreement, Lantheus will pay an upfront payment and potential additional development and commercial milestone payments. Additionally, Lantheus will pay double-digit royalty payments for research revenue and commercial sales.
Prothena Corporation plc announced positive topline
Phase I single ascending dose (SAD) study results for
PRX005, a potentially best-in-class investigational tri-epitopic antibody for the treatment of Alzheimer's disease that specifically binds with high affinity to the R1, R2, and R3 repeats within the microtubule binding region (MTBR) of tau and targets both 3R and 4R tau isoforms. The results of the study found all three dose level cohorts of PRX005 to be generally safe and well tolerated, meeting the Phase 1 SAD study primary objective. None of the treatment emergent adverse events (TEAE) were serious. No clinically relevant changes were observed in other safety parameters. PRX005 also met key pharmacokinetic (PK) and immunogenicity secondary endpoints.
Eli Lilly and Company announced the
U.S. Food and Drug Administration (FDA) has issued a
complete response letter for the accelerated approval submission of
donanemab for the treatment of early symptomatic Alzheimer's disease due to the limited number of patients with at least 12 months of drug exposure data provided in the submission. No other deficiencies in the application were noted.The confirmatory Phase 3 TRAILBLAZER-ALZ 2 trial remains ongoing, with topline data read-out expected in Q2 2023, and will form the basis of donanemab's application for traditional approval shortly thereafter. Lilly will continue to work with the FDA to evaluate the fastest pathway to make this potential treatment option widely available to patients.
Coya Therapeutics, Inc. announced the recent publication of an article entitled "Ex vivo expanded human regulatory T cells modify neuroinflammation in a preclinical model of Alzheimer's Disease" in the peer-reviewed journal Acta Neuropathologica Communications.Furthermore, Treg-treated mice showed a significant reduction in total and plaque-associated microglia as well as reactive astrocytes in the dentate gyrus and frontal cortex versus untreated mice. The reduction in the number of plaque-associated glial cells and suppression of pro-inflammatory signaling pathways within these cells following Treg therapy may attenuate the contribution of these toxic glial cells in AD pathology resulting in mitigation of amyloid burden.
Eli Lilly and Company announced that donanemab met all primary and secondary endpoints for the 6-month primary outcome analysis in the
Phase III TRAILBLAZER-ALZ 4 study, providing the first active comparator data on amyloid plaque clearance in patients with early symptomatic Alzheimer's disease treated with amyloid-targeting therapies. Donanemab is an investigational antibody that targets a modified form of beta-amyloid plaque called N3pG.
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Alzheimer's Disease Pipeline Report
The Alzheimer's disease pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage Alzheimer's disease drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the Alzheimer's disease clinical trial landscape.
Alzheimer's Disease Overview
Alzheimer's disease (AD) is a slowly progressive brain disease that manifests itself many years before symptoms appear. It is the leading cause of dementia, accounting for 60% to 80% of cases. The accumulation of the protein fragment beta-amyloid (plaques) outside neurons in the brain and twisted strands of the protein tau (tangles) inside neurons are the hallmark pathologies of Alzheimer's disease.
Alzheimer's disease is a progressive disease, so the symptoms worsen over time. Memory loss is a key feature, and it is often one of the first Alzheimer's disease symptoms to appear. The other Alzheimer's disease symptoms include cognitive deficits, problems with recognition, problems with spatial awareness, and others.
A thorough clinical evaluation, a detailed patient history, and various specialized tests are used to make an Alzheimer's disease diagnosis. Clinical diagnosis, which is usually made during the early stages of the disease, lumbar puncture, and imaging studies are all methods of diagnosing Alzheimer's disease.
Treatment for Alzheimer's disease includes options that may alleviate symptoms and improve quality of life. To treat cognitive symptoms, the FDA has approved two types of medications to treat cognitive symptoms: cholinesterase inhibitors (Aricept, Exelon, Razadyne) and memantine (Namenda). Other non-pharmacological therapies are also used to maintain or improve cognitive function, daily living ability, or overall quality of life.
Find out more about drugs for Alzheimer's disease @
New Alzheimer's Disease Drugs
A snapshot of the Alzheimer's Disease Pipeline Drugs mentioned in the report:
Learn more about the emerging Alzheimer's disease pipeline therapies @
Alzheimer's Disease Clinical Trials
Alzheimer's Disease Therapeutics Assessment
Alzheimer's disease pipeline report proffers an integral view of Alzheimer's disease emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration.
Scope of the Alzheimer's Disease Pipeline Report
Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination
Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III
By Route of Administration: Oral, Parenteral, Intravenous, Subcutaneous, Topical
By Molecule Type: Monoclonal Antibody, Peptides, Polymer, Small molecule, Gene therapy
By Mechanism of Action: Amyloid beta-protein inhibitors, Inflammation mediator inhibitors, Immunostimulants, Tumour necrosis factor alpha inhibitors, Microfilament protein modulators, Angiogenesis inhibitors, Colony stimulating factor inhibitors, Coronavirus-3C-like-proteinase inhibitors, Endopeptidase Clp inhibitors, Focal adhesion protein-tyrosine kinase inhibitors, Lyn protein-tyrosine kinase inhibitors, Macrophage colony-stimulating factor receptor modulators, Mast cell inhibitors, Platelet-derived growth factor receptor antagonists, Protein tyrosine kinase inhibitors, Proto oncogene protein c-kit inhibitors, Proto-oncogene protein c-fyn modulators, Type 3 fibroblast growth factor receptor antagonists
Key Alzheimer's Disease Companies: Biogen, AZTherapies, Cerecin, Neurotrope, Synaptogenix, INmune Bio, Cassava Sciences, EIP Pharma, Neuraly, AB Science, Cortexyme, Anavex Life Sciences, Athira Pharma, Time Therapeutics, Denali Therapeutics Inc., Alector Inc., Lexeo Therapeutics, TrueBinding, Inc., Vaccinex Inc., Annovis Bio Inc., Eisai Inc., Hoffmann-La Roche, Ionis Pharmaceuticals, Inc., Otsuka Pharmaceutical Co., Ltd., Cognition Therapeutics, Merck Sharp & Dohme LLC, ImmunoBrain Checkpoint, AbbVie, AriBio Co., Ltd., Oryzon Genomics S.A., Eli Lilly and Company, Neurokine Therapeutics, Excelsior, Seelos Therapeutics, Inc., Janssen Research & Development, LLC, Shanghai Hengrui Pharmaceutical Co., Ltd., reMYND, Alzinova AB, VTBIO Co. LTD, BioVie Inc., Prothena Corporation plc, Coya Therapeutics, Inc., and others.
Key Alzheimer's Disease Pipeline Therapies: ALZT-OP1, Tricaprilin, Bryostatin-1, INB03, Sumifilam, Neflamapimod, Pegylated exenatide, NLY-02, Masitinib, Atuzaginstat, COR588, Blarcamesine, NDX-1017, Bromocriptine, DNL788, AL002,CMS121, LX1001, TB006, Pepinemab, Posiphen, E2814, RO7126209, IONIS MAPTRx, Brexpiprazole, CT1812, MK-1942, IBC Ab002, ABBV-916, AR1001, ORY-2001, LY3372689, MW150, EX039, SLS-005, Seltorexant, Donanemab, SHR-1707, REM0046127, ALZ-101, VT301, NE3107, PRX005, MK-6240, and others.
Dive deep into rich insights for new drugs for Alzheimer's disease treatment; visit @
Alzheimer's Disease Medications
Table of Contents
For further information on the Alzheimer's disease pipeline therapeutics, reach out @
Alzheimer's Disease Drug Treatment
Alzheimer's Disease Epidemiology
Alzheimer's Disease Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted Alzheimer's disease epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan.
Alzheimer's Disease Market
Alzheimer's Disease Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Alzheimer's disease companies including
AZTherapies, Cerecin, Neurotrope, Lyndra, AC Immune, INmune Bio, Cassava Sciences, EIP Pharma, Neuraly, AB Science, Cortexyme, among others.
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Market Insight, Competitive Landscape, and Market Forecast – 2027 report delivers an in-depth understanding of market trends, market drivers, market barriers, and key neurostimulation devices companies, including
Medtronic PLC, Cyberonics, Boston Scientific Corporation, Abbott Laboratories, among others.
Deep Brain Stimulation Devices Market
Deep Brain Stimulation Devices
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Alzheimer's research is having a moment, and the discovery of novel biomarkers is enabling progress far beyond diagnostics.
Since their role in Alzheimer's disease (AD) was first identified in the 1980s, amyloid beta and tau proteins have been the hallmark AD biomarkers. And while the anti-amyloid theory is regaining traction, researchers now understand there are many pathologies and co-pathologies involved in the disease.
Laura Nisenbaum, Ph.D.
Laura Nisenbaum, Ph.D., executive director of drug development at the Alzheimer’s Drug Discovery Foundation (ADDF), envisions a future of precision medicine, drug regimens tailored to each patient - as is currently the case in cancer therapeutics.
“Alzheimer’s is about 30 years behind where cancer research is,” she said.
Utilizing extensive biomarker testing, physicians could prescribe a combination of therapies based on the specific physiology of their patient’s unique disease.
Combining different therapies would allow us to “go beyond the type of effects that are beginning to be seen in the anti-amyloid base,” Nisenbaum said.
Novel Biomarkers Inform Trials
Historically, up to 30% of patients enrolled in AD drug trials didn’t actually have the disease, as defined by pathology, she said.
The advancement and accessibility of biomarker testing lends itself to more accurate diagnoses, enabling recruitment of the right people into the right trials.
Research suggests degeneration from AD begins 15-20 years before clinical manifestation, making early detection critical to treatment.
Backed by ADDF’s Diagnostics Accelerator, molecular diagnostics company DiamiR is developing CogniMIR, a blood-based assay that measures levels of specific microRNAs to detect synaptic dysfunction and neurodegeneration before clinical presentation. It can also predict disease progression.
Foregoing the needle, Israel-based NeuraLight is developing a platform to detect biomarkers in neurological diseases, including AD, utilizing oculometric measures.
NeuraLight’s platform monitors micro-movements of the eye.
Micha Breakstone, Ph.D
"[This provides] a signature of the near degeneration of the brain…, the acuity of the disease and how much it has progressed,” Micha Breakstone, Ph.D., CEO and co-founder, told BioSpace.
The ocular markers are highly sensitive to indicate change. They also offer an objective marker that “reduces noise and variability” compared to other measurements that are more subjective and “questionable,” Breakstone said.
The technology not only opens the door for earlier, non-invasive diagnosis, but it can also detect efficacy early in clinical development, leading to less time lost on trial flops.
Biomarkers can help companies “make rigorous decisions about whether to continue to explore a particular therapeutic target or mechanism of action, or to move to another approach,” Nisenbaum said.
TDP-43 and ApoE4
As biomarkers evolve to improve clinical trial outcomes, they may also have a role in building the therapeutic pipeline.
The TDP-43 protein has already shown promise as a druggable biomarker for ALS, a neurodegenerative disease with some pathological connections to AD.
PrimeC, a combination therapy being developed by NeuroSense Therapeutics, reduced functional and respiratory deterioration and led to statistically significant changes in ALS-related biological markers in a Phase IIa study.
TDP-43 is known to cause neuroinflammation, and its characteristics suggest an interaction between this biomarker and amyloid beta or tau.
In January, NeuroSense released results from a biomarker study that showed the protein was elevated in AD patients compared with a control group.
Alon Ben-Noon, co-founder and CEO of NeruoSense, started the company to tackle ALS.
“Honestly, I didn’t think at the time about Alzheimer’s at all,” he told BioSpace. But, as the data progressed and the biomarker study revealed the huge potential, he deemed it worth the effort to try to advance another therapy in the AD space.
Based on the biomarker study, NeuroSense will commence a Phase II double-blind proof-of-concept study to test the therapy in AD in the first half of 2023. The company has partnered with NeuraLight to track ocular biomarkers in clinical trials.
Another prime biomarker for the development of Alzheimer's disease is the apolipoprotein E (APOE)4 gene variant. While 15% of healthy people have the variant, it is present in over 50% of AD patients. APOE4 is considered to be the strongest risk factor gene for the disease.
Armed with that knowledge, Lexeo Therapeutics is developing LX1001, an AAV-based gene therapy, for patients with this mutation.
LX1001 is designed to work by delivering the apolipoprotein E2 (APOE2) gene into the central nervous system in an attempt to halt or slow disease progression.
The gene therapy is currently in Phase I/II trials.