China’s regulatory agency has granted a conditional approval to an Alzheimer’s drug from Shanghai Green Valley Pharmaceuticals that is due to start phase 3 trials in the US and Europe next year.
The approval comes with the caveat that further research on Oligomannate (sodium oligomannurarate or GV-971) – a drug derived from marine algae – is required to show long-term safety and efficacy, according to China’s National Medical Products Administration (NMPA).
Nevertheless, if its efficacy is proven in further testing it could represent a step forward in a disease that has eluded the best efforts of researchers around the world for decades, with billions of dollars spent on dozens of failed drug candidates.
Oligomannate is the first new drug to be approved for Alzheimer’s since memantine, which was approved in Europe in 2002 and the US in 2003.
Earlier this year, Green Valley said that patients with mild-to-moderate Alzheimer’s who received a twice-daily oral dose of Oligomannate over 36 weeks showed a statistically-significant improvement over placebo on the ADAS-Cog 12 scale used to test cognitive function.
The mean difference between GV-971 versus placebo in ADAS-Cog12 score at the end of the study was 2.54. A three-point decline on the scale is viewed as a clinically significant worsening of Alzheimer’s symptoms.
Xiao Shifu of Shanghai Jiao Tong University, one of the principal investigators in the study, said that the results “showed rapid onset of efficacy of Oligomannate within four weeks, and patients’ cognitive function continued to improve”. He added: “The treatment was safe during the 36-week clinical trial.”
Oligomannate works in a different way to many of the failed drugs in Alzheimer’s, which have focused on neurotoxic beta amyloid that forms the characteristic plaques seen in the brains of people with the disease.
Green Valley says Oligomannate inhibits beta amyloid fibril formation, but also reduces hyperphosphorylation of tau protein – results in the neurofibrillary tangles that are also a hallmark of the disease – as well as dampening down inflammation in the peripheral and central nervous system and restoring the natural balance of microorganisms in the gut.
Green Valley says it will launch Oligomannate in China ‘very soon’ while also carrying out trials to support regulatory filings in other ‘selected countries’.
A phase 3 trial called GREEN MEMORY will include sites in the US, Europe and Asia and is due to get underway in early 2020.
Responding to the announcement, Alzheimer’s Research UK’s director of research Carol Routledge commented: “It’s good to see that drug regulators in China are prioritising emerging treatments for Alzheimer’s, but we do still need to see more evidence that this drug is safe and effective.”
“For any potential drug to gain a stamp of approval by regulators in the UK, we’ll need to see larger trials in countries around the world to back up the evidence from China. We must await full data from this study and further clinical trials before we can fully assess the potential of Oligomannate to improve the lives of people with Alzheimer’s disease,” she added.
Current drugs for Alzheimer’s like NMDA glutamate antagonist memantine and cholinesterase inhibitors such as donepezil and galantamine have limited efficacy and don’t address the underlying mechanism of cognitive decline.
Most of the research spend on disease-modifying therapies has gone on amyloid-targeting drugs, with little success. However last month Biogen and Eisai said that their amyloid-targeting drug aducanumab –written off earlier this year – had shown activity on a re-analysis of data from clinical trials and would be filed for approval.