- Prolonged treatment with Alzheon Inc.'s lead candidate helped preserve cognitive functions within a subgroup of Alzheimer's disease (AD) patients, suggesting the drug may offer "potential disease modifying effects," according to a study abstract presented at the Alzheimer's Association International Conference in London.
- The Phase 3 trial enrolled more than 1,000 mild to moderate AD patients who received either placebo or one of two doses — 100 mg or 150 mg — of ALZ-801 (tramiprosate) over 78 weeks. Following that investigation, participants could continue on to a 52-week blinded extension study in which they were all put on 150 mg regimens of Alzheon's drug.
- Results showed that, among patients homozygous for apolipoprotein E4 (APOE4), a known genetic risk factor for AD, those who had taken the larger dose of ALZ-801 throughout the 130 weeks of observation demonstrated greater cognitive benefits than those who switched from placebo to the 150 mg dose.
Alzheon CEO Martin Tolar said back in 2015 that his company was going to be the first to market with a disease-modifying treatment for Alzheimer's disease. But it might only work for a small patient population. Alzheon's drug is a prodrug version of tramiprosate, an Alzheimer's compound that failed in Phase 3.
It's the lack of disease-modifying drugs that makes Alzheon's data important; if continued research shows ALZ-801 can keep cognitive decline in AD patients at bay, even if just for the subpopulation homozygous for APOE4, that would be a huge breakthrough for the clinical-stage drugmaker as well as the wider pharmaceutical industry.
"All of our research and insights have brought us to the point where we can confirm how ALZ-801 blocks Alzheimer’s amyloid pathology, and confidently pursue our goal of directing an oral medicine for the Alzheimer’s patients who will most benefit from the treatment," Alzheon CEO Martin Tolar said in a July 17 statement.
Apolipoproteins are proteins responsible for transporting fats throughout the body, with apolipoprotein E (APOE) being one type. Of the three main APOE alleles, dubbed 2, 3 and 4, researchers believe the latter contributes to the development of the cytotoxic beta amyloid oligomers that are key to the progression of AD. Though the estimates vary, a growing body of evidence suggests that patients likelihood of getting the disease increases with the number of APOE4 alleles they posses.
The extended portion of Alzheon's late-stage study enrolled 735 patients, including 104 who were APOE4 homozygotes. According to the drugmaker, ALZ-801 demonstrated the largest efficacy in APOE4 homozygotes with mild AD — those who took the 150 mg doses over 130 weeks scored 3.9 points better on the Alzheimer's Disease Assessment Scale-cognitive test and had a "positive trend" on the Clinical Dementia Rating scale versus those who went from placebo to the largest dose.
Alzheon explained the novel mechanism of action for tramiprosate, the active ingredient, works by having a "multi-ligand interaction" with beta amyloid 42 monomers, which thereby stabilizes them and preventing them from aggregating to form oligomers.