Background

Alzhemed was designed as an anti-amyloid therapy. It is a patented variant of the amino acid taurine, which is reported to inhibit the interaction of Aβ with endogenous glycosaminoglycans and thereby prevent β-sheet formation. This drug originated in a screen for low-molecular-weight molecules that mimic glycosaminoglycans and can therefore antagonize the interaction of Aβ with endogenous glycosaminoglycans. Glycosaminoglycans have been reported to promote Aβ aggregation and plaque stability (Gupta-Bansal et al., 1995), and Alzhemed has been proposed to interfere with amyloid fibril formation and deposition into plaques.

In vitro, Alzhemed was reported to preferentially bind soluble Aβ, inhibit its aggregation, fibrillogenesis, and neurotoxicity (Gervais et al., 2001; Gervais et al., 2007). A decade later, multiple Alzhemed molecules were reported to bind to one Aβ42 monomer and prevent fibrillar seed formation and neuronal toxicity (Kocis et al., 2017). It takes a 1,000-fold molar excess of Alzhemed over Aβ to prevent oligomer formation. In TgCRND8 mice, systemic Alzhemed reduced brain amyloid by 30 percent. In contrast, the drug reportedly promotes abnormal aggregation of tau (Sept 2007 news).

Homotaurine is also a GABA A receptor agonist (Caltagirone et al., 2012).

Findings

In a Phase 2 study beginning in 2002, 58 people with mild to moderate AD received 50, 100, or 150 mg Alzhemed or placebo daily for three months. Endpoints included CSF Aβ and tau concentrations, and cognitive measures. Subsequently, 42 participants continued into open-label dosing with 150 mg for 17 months. The drug appeared safe, and reduced CSF Aβ42 after three months (Aisen et al., 2006). In the long-term extension, people with mild AD were reported to have stayed cognitively stable at 20 months (Jan 2007 conference news).

In June 2004, Alzhemed became the first anti-amyloid drug to enter Phase 3. This study enrolled 1,052 people age 50 or older with mild to moderate AD at 67 centers in the U.S. and Canada. They received 100 or 150 mg Alzhemed or placebo daily for 18 months, followed by one year of open-label extension. Primary endpoints were change in the ADAS-Cog and CDR-SB. The trial also tracked brain volume with MRI, and CSF Aβ and tau concentrations. A similar study in Europe began enrolling 930 participants in 2005.

In mid-2007, NeuroChem announced the trial had failed to measure an improvement in cognition in the North American trial (Aug 2007 news). In November 2007, the company stopped the European trial, but continued the open-label extension of the North American trial. Results were subsequently published (Aisen et al., 2011).

After discontinuing clinical development, NeuroChem pivoted to marketing Alzhemed as a nutritional supplement (Nov 2007 conference news). NeuroChem changed its name to Bellus Health and, in 2008, began to sell Alzhemed under the brand name Vivimind™ over the counter in Canada (Oct 2008 news). In 2011, the FDA refused to permit sales of Vivimind™ in the U.S., on the grounds that homotaurine did not qualify as a nutrient (see news).

Nine years later, a subgroup analysis of the Phase 2 and 3 data, including from their open-label extensions, was reported to indicate that the drug had slowed cognitive decline in ApoE4 homozygotes, and perhaps halted decline in those with mild AD (Abushakra et al., 2016; Abushakra et al., 2017). In 2013, the U.S. startup Alzheon licensed ALZ-801, a prodrug version of Alzhemed currently in development for Alzheimer’s disease. 

For details on Alzhemed trials, see clinicaltrials.gov.