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pharmafile | September 4, 2008 | News story | Research and Development |Â Â Alzheimer'sÂ
Attention shifts from beta-amyloid to tau in the hunt for an Alzheimer's disease therapy
In years to come, scientists and pharmaceutical companies may look at the 2008 International Conference on Alzheimer's disease (ICAD) as a water-shed in the development of truly effective disease modifying treatments. As beta-amyloid focused treatments continue to produce disappointing results, approaches focused on tau tangles have now emerged as the most promising candidates.
In 1906 Dr Alzheimer described "miliary foci" (beta-amyloid plaques) and "dense bundles of fibrils" (tau neurofibrillary tangles) when first classifying Alzheimer's disease in a postmortem examination. Over the last 20 years researchers have focused predominantly on beta-amyloid as the primary Alzheimer's disease drug and research target. However, there was a small group of Alzheimer's disease researchers who believed that tau tangle formation was a more prominent feature in Alzheimer's disease pathology, supported by a closer correlation between dementia pre-mortem and tau tangle density post-mortem than that seen with beta-amyloid plaques.
Results presented at the ICAD conference this week suggest that the tau protein may well be the more viable target for clinical benefit in Alzheimer's disease. Trials of two beta-amyloid focused treatments found disappointing results, whereas developers of two tau focused treatments presented surprising and very promising positive results.
TauRx Therapeutics' tau focused treatment Rember (methylthioninium chloride) has captured the mass media's attention following announcement at the conference of the most promising Alzheimer's disease clinical trial results so far. TauRx tested the drug in a Phase II clinical trial involving 321 patients with mild and moderate Alzheimer's disease. The decline seen in patients treated with Rember was not significantly different from their starting score to the assessment at one year or 19 months, indicating a complete halting of disease progression.
Earlier in the week a 144 patient Phase IIa clinical trial of Allon Therapeutics' AL-108, an experimental therapy designed to combat tau neurofibrillary tangles in amnestic mild cognitive impairment patients (a condition believed to represent early Alzheimer's disease), showed a 62% improvement from baseline on short-term memory recall (statistically significant improvement over placebo).
Meanwhile, further analysis of Phase II results from Wyeth/Elan's anti-amyloid focused therapy bapineuzumab (AAB-001), previously thought to be the most promising pipeline candidate, have led to concern over the drug's safety. As a result of this, and the additional competition from emerging Phase II candidates, the share price of both companies has declined significantly in recent days. In addition, full results from a Phase III trial of Myriad's Flurizan (tarenflurbil), another anti-amyloid therapy, have confirmed that the drug failed to achieve significant effect on its primary endpoints.
A lot is at stake for pharmaceutical companies interested in the Alzheimer's disease market. With a high prevalence, aging population, and high unmet need, a disease modifying Alzheimer's treatment could gain in excess of $10 billion annual revenues. The tau focused treatments now look best placed to gain access to this considerable market opportunity.
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