China's Alzheimer’s Drug Approval Raises Hopes and Skepticism
Chinese company Shanghai Green Valley Pharmaceuticals received conditional approval to treat Alzheimer’s disease in China for its Oligomannate (GV-971). The news was met by hope, since it would break a long drought of approved therapies for Alzheimer’s, but questions as well—it sounds a little too good to be true.
China’s National Medical Products Administration (NMPA), the country’s equivalent of the U.S. Food and Drug Administration (FDA), approved Oligomannate for “mild to moderate Alzheimer’s disease (AD) and improving cognitive function.” It was granted fast-track review in November 2018.
The drug is derived from seaweed. The company reported that its Phase III clinical trial was a multicenter, randomized, double-blind, placebo-controlled, parallel-group 36-week study led by Peking Union Hospital and Shanghai Jiaotong University Medical School Mental Health Center. The trial was run at 34 Tier-1 hospitals across China on a total of 818 patients who had been diagnosed with mild to moderate Alzheimer’s disease. It was conducted in collaboration with IQVIA (formally Quintiles) and Signant Health (formerly Bracket) and other partners.
One of the things the company reported that has raised eyebrows is that the drug statistically improved cognitive function in the patients as early as week 4. This would be a very quick patient response—and for that matter, given that many Alzheimer’s studies run for years, a 36-week study is at least half the length of a typical Alzheimer’s trial.
Derek Lowe, in his “In the Pipeline” blog in Science Translational Medicine, notes that the drug apparently doesn’t focus on beta-amyloid, citing a September paper that “concentrates instead on a gut-bacteria immunology/inflammation mechanism, which frankly is more plausible in its way than any effect on beta-amyloid. Not least because it’s quite difficult to imagine a mannan polysulfate making its way past the blood-brain barrier. But the gut-bacteria explanation, which quite interesting, does make some leaps along the way. People who have been following this field (gut microbiota influencing human disease) will appreciate that it can be very difficult to prove real connections, and that the number of confounding variables is huge.”
The paper Lowe cites was published in the journal Cell Research that described the connection in mice between an altered gut microbiome and the neuroinflammation that some research associates with Alzheimer’s. The paper argued that Oligomannate suppressed the bacterial imbalance in the mice’s guts and “harnesses neuroinflammation and reverses the cognition impairment.”
The full data on the drug hasn’t been made available. The conditional approval means it will make it to the market in China by the end of the year, but will be required to submit additional research on the drug’s mechanism of action and long-term safety and effectiveness to the NMPA.
The company plans to launch a global Phase III clinical trial in 2020 in hopes of being able to file approval in other countries, including the United States.
“It’s good to see that drug regulators in China are prioritizing emerging treatments for Alzheimer’s, but we do still need to see more evidence that this drug is safe and effective,” said Carol Routledge, the director of research at Alzheimer’s Research UK. “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’re always excited to have a new potential treatment,” Joy Snider, a neurologist at Washington University in St. Louis, told STAT, “but I certainly would not prescribe it to my patients based on a single study or another country’s approval until we know more about it.”