The Alzheimer’s Association International Conference (AAIC) was held in Toronto, Canada from July 24-28, 2016. This year’s meeting went beyond the talk of beta-amyloid monoclonal antibodies as potential disease-modifying therapies. One of the main highlights of the conference were the results of LMTX Phase III study. The findings created much of the buzz at the conference considering that this is the first tau-aggregation inhibitor to reach Phase III development. In parallel, there were also several scientific presentations on tau pathology, stressing on its importance and ties to the progression of the disease. The heightened interest in tau-targeting therapies is also triggered by the development of tau PET tracers.

In addition to tau, there were also several presentations on the early Phase results of BACE inhibitors, with many big players involved highlighting the renewed interest around this area of development. Other presentations included new clinical data for some of the symptomatic treatments and additional analysis and trial details for some of the ongoing late-stage amyloid-targeting antibodies as an ongoing effort to identify effective disease-modifying therapies for Alzheimer’s disease. Lastly, the quest to identify diagnostic, mechanistic and prognostic biomarkers still continues, with some exploratory studies aimed at identifying cheaper and easier to use biomarkers as an effort to increase accessibility to patients. A biomarker that is easily accessible and inexpensive could make the difference between physicians intervening in the early stages of the disease when symptoms are not yet that apparent to late stage dementia.

Key Highlights

• TauRx Therapeutics presented the results of the Phase III TRx-237-015 study. In the full study population, LMTX failed to demonstrate treatment benefit in patients with mild to moderate Alzheimer’s disease receiving background therapy. When a pre-specified subgroup analysis was carried out on patients receiving LMTX exclusively as a monotherapy versus the pooled group, a statistically significant treatment benefit emerged. However, the ambiguity of the results and the questionable analysis will make the case particularly challenging when presenting this dataset to the US Food and Drug Administration.
  
  
• Roche presented the Phase III trial design of CREAD where crenezumab is evaluated in patients with prodromal to mild Alzheimer’s disease. Several adjustments were made to the design of CREAD. Patients with earlier stages of Alzheimer’s disease, specifically those with evidence of amyloid pathology, were included in the study. Furthermore, the crenezumab dose was increased four-fold from that used in ABBY. These adjustments are in line with the view that disease-modifying therapies should be targeting earlier stages of the disease, in patients with evidence of the Alzheimer’s disease pathology, and at a dose large enough to dislodge the amyloid system in the brain, such that it is translated into a clinical response.
  
  
• BACE inhibitors garnered a fair share of attention with findings from several early stage developments presented at the conference.
  
  
• Anavex presented preliminary efficacy data from the open-label, single-arm, dose-finding Phase IIa trial of Anavex 2-73 in a very limited number of mild to moderate Alzheimer’s disease patients that suggested cognitive and functional stability in these patients. Although placebo effect cannot be ruled out, the signal is strong enough to proceed with a placebo-controlled trial.
  
  
• Pfizer presented the failed Phase II SAM-760 study of the adjunctive therapy PF-05212377 in mild to moderate Alzheimer’s disease patients with neuropsychiatric symptoms. The trial was stopped due to meeting futility criteria in the first interim analysis. Details of the trial design, study population and pharmacological profile may explain differences in outcomes compared to other 5HT6 receptor antagonists in the symptomatic treatment of patients with Alzheimer’s disease.

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