- Alzheon said it is advancing plans for a Phase 3 clinical trial for its Alzheimer’s disease candidate, ALZ-801, following a re-evaluation of previous data. The new analysis, reported in The Journal of the Prevention of Alzheimer’s Disease, was a reversal of previous study results that failed to prove impact of beta-amyloid, the company said.
- The small drugmaker plans to evaluate ALZ-801, an optimized oral prodrug of tramiprosate, as a potential disease-modifying agent to target 65% of mild to moderate AD patients with a genetic condition, known as APOE4/4 homozygotes.
- Alzheon has joined a group of much larger drugmakers such as Eli Lilly, Biogen and others, targeting amyloid-related therapies for the treatment of Alzheimer’s disease, which has generally baffled drugmakers. The development landscape has been marked by a string of failures in developing medicines to combat the disease.
When it comes to Alzheimer’s drug development, there have been many flops along the way by big and small drug companies, and Alzheon has been there, too. Ironically, Alzheon’s previously unsuccessful studies with beta-amyloid drugs have provided new insights that the company now says are showing new possibilities and momentum for development of ALZ-801.
Alzheon is now among the companies focusing on genetically defined patients to find a pathway to treat Alzheimer’s disease. The key may be targeting APOE4, the company says, a major genetic risk factor in many Alzheimer’s patients and also associated with earlier onset AD, severe symptoms and more rapidly progressive illness. The gene, formally called apolipoprotein E (APOE), has been linked to an increased risk of Alzheimer’s.
The Phase 3 study results showed a gene-dose effect at the high dose of tramiprosate (150 mg, twice daily), with patients with two APOE4 alleles (APOE4/4 homozygotes) showing the largest clinical benefit. Those with one APOE4 allele (APOE4 heterozygotes) showed an intermediate benefit, while APOE4 non-carriers showed no benefit from tramiprosate, the company said.
The result is new momentum and a turn-of-events for the development of ALZ-801, said Martin Tolar, founder, president and CEO of Alzheon. "This new insight shows how we can apply a precision medicine approach in AD and develop this drug for the right patients, namely patients with the APOE4 genotype," said Tolar.
Tolar said in a statement he believed the study marked the first time there were clinical benefits of an amyloid targeted agent associated with APOE4 alleles in Alzheimer’s patients. For the company, it couldn’t happen any sooner, as other drugmakers such as Biogen, Merck and Anavex have candidates who are targeting amyloid-recreated therapies.
Alzheimer’s disease has a history of humiliating drug makers. In July alone, there were several high profile setbacks reported. Those failures included TauRx Therapeutics' treatment, a joint development among Roche and Evotec, for its drug sembragiline that did not demonstrate cognitive benefit after a year, and Lundbeck’s idalopirdine, an experimental drug for mild to moderate Alzheimer’s disease.
With the latest study results, Alzheon has reinforced its commitment to advance ALZ-801 into studies of APOE4/4 homozygous AD patients, Tolar added. "We are preparing to advance ALZ-801, a promising new treatment for Alzheimer’s disease into the clinical studies in 2017," he said.