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Competitor Analysis: Tau and Amyloid Beta Targeted Therapy of Alzheimer’s Disease
La Merie Publishing, Aug 2010, Pages: 105
The present Competitive Intelligence Report about Tau and Amyloid Beta Targeted Therapy of Alzheimer’s Disease provides a competitor evaluation in the field of therapeutic vaccines, antibodies and small molecules targeting Tau and/or Amyloid Beta for treatment of Alzheimer’s disease as of August 2010. Purchase of the downloadable pdf report includes a 6-month online access to the data of the report and any updates since the publication date. Credentials to access the database will be sent by e-mail and allow online work with the project data to print or export an individual report.
One of the main pillars of current drug discovery and development activities in the pharmaceutical industry for Alzheimer’s disease is prevention of the accumulation of misfolded proteins, i.e. amyloid beta and tau. At present, the majority of approaches are directed to the amyloidogenic pathway. Amyloid beta peptides derive from amyloid precursor protein (APP) by proteolytic cleavage by beta secretase and gamma secretase.
Thus, inhibitors of beta secretase (or beta-site APP-cleaving enzyme, BACE-1) are a main area of drug discovery complicated by the substate diversity of BACE-1 and the need to pass the blood-brain barrier (BBB) which explains that only very few inhibitors entered clinical development with no compound in phase III, but many ongoing discovery programs. The first representative of the class of inhibitors and modulators of gamma secretase has entered phase III but the studies recently failed to meet the efficacy endpoint and even worsened the clinical outcomes in the studies. It remains to be seen whether follower programs in clinical phases I and II will suffer the same fate or can be differentiated from Lilly’s semagacestat. Most of the gamma secretase inhibitors in development are Notch-sparing molecules, thereby avoiding typical side effects of the Notch signaling pathway, e-g. gastrointestinal and hematological toxicities.
Increasing the activy of alpha secretase is another means to reduce the activity of beta secretase. A number of compounds with different primary mechanisms of action are in clinical and preclinical development.Strong efforts are made by the industry in immunotherapy against amyloid beta to inhibit generation of toxic amyloid beta aggregates and remove soluble and aggregated amuyloid beta. At least eight therapeutic vaccines against amyloid beta are under clinical investigation and more candidates are in preclinical R&D stages. Passive immunotherapy with therapeutic antibodies against amyloid beta has already reached phase III testing in clinical studies. Ten antibody projects are in clinical or IND enabling study phases and more than ten candidates in preclinical stages. Intravenous infusion of human-plasma derived immunoglobulin preparations which contain naturally occurring plyclonal anti-amyloid beta antibodies are also in advanced clinical testing.
Another approach is the development of CNS-bioavailable compounds that inhibit amyloid beta aggregation or disintegrate amyloid beta oligomeric species without being toxic or immunogenic. The second generation of such molecules has at least ten representatives in clinical studies up to phase II.
The cytoplasmic protein Tau has recently gained much interest as a target for new therapies of Alzheimer’s disease where it is abnormally phosphorylated resulting in the generation of neurofibrillary tangles (aggregates) toxic to neurons. The main tau-targeted approaches include molecules inhibiting hyperphosphorylation and molecules that inhibit tau aggregation or promote aggregate disassembly. Only a few molecules have reached clinical stages, but strong research efforts are undertaken to come up with more clinical candidates.
The report includes a compilation of currently active projects in research and development of vaccines, antibodies, small molecules, proteins and peptides targeting Tau and/or the amyloid beta pathway. In addition, the report lists company-specific R&D pipelines of Tau and Amyloid Beta Targeted Therapeutics for Alzheimer’s disease. Competitor projects are listed in a tabular format providing information on:
- Drug Codes,
- Target / Mechanism of Action,
- Class of Compound,
- Company
- Product Category
- Indication,
- R&D Stage and
- additional comments with a hyperlink leading to the source of information.
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