It has been almost two decades since any Alzheimer’s drug was approved. Oligomannate has received scant attention in the United States during its development.
Although full data on the drug have not yet been made available, the conditional approval by regulators means Oligomannate, also known as GV-971, will on the market in China by the end of the year, Green Valley said. The company will have to submit additional research on the mechanism of the drug and its long-term safety and effectiveness to the country’s National Medical Products Administration, Reuters reported. Green Valley also said it would launch a global Phase 3 trial next year in hopes of filing for approval in other countries as well.
“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,” Carol Routledge, the director of research at Alzheimer’s Research UK, said in a statement. “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.”
Outside experts said they would want the full data to show exactly how cognitive function improved for patients on the drug versus those on placebo, and how meaningful that was in the patients’ lives.
Instead of being designed to sweep away protein buildups in the brain, as has been the case with dozens of other experimental Alzheimer’s treatments, Oligomannate was developed to modulate the connection between the brain and the bacterial communities in the gut known as the microbiome.
The connection between the microbiome and overall health is the subject of a relatively new and evolving field of research, with some scientists seeking to understand how bacteria can influence the emergence of disease, including Alzheimer’s.
Maria Carrillo, the Alzheimer’s Association’s chief science officer, said the development of Oligomannate reflected how the field had expanded beyond drugs that targeted the accumulation of protein in the brain, which, she said, “is the first step necessary toward a combination approach to treat Alzheimer’s dementia and all dementia.”
For the next trial, which Green Valley said will include U.S. sites, Carrillo said she was curious to see how the drug fared in a more diverse population and that she hoped researchers would track patients for longer. Often, Phase 3 trials in Alzheimer’s last for twice as long as the nine-month trial Green Valley ran in China, she said.
And Dr. Joy Snider, a neurologist at Washington University in St. Louis, said she hoped the next trial would include more people than the roughly 800 enrolled in the earlier Phase 3 trial.
“We’re always excited to have a new potential treatment,” Snider said, “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.”
In September, a group of Chinese scientists, including some from Green Valley, published a study in the journal Cell Research that outlined the connection in mice between an altered gut microbiome and the neuroinflammation that some researchers think contributes to Alzheimer’s. They reported that Oligomannate “suppresses” the bacterial imbalance in the mice’s guts and “harnesses neuroinflammation and reverses the cognition impairment.” They added that the results of the mouse study “suggest a novel strategy” for Alzheimer’s therapies “by remodeling the gut microbiota.” (Many experimental therapies have cured diseases in mice without ever demonstrating any benefit in people.)
The completed trial was not designed to demonstrate that the drug apparently worked through that mechanism, said Dr. Jeffrey Cummings of the Cleveland Clinic, who has been an adviser to Green Valley for about two years. But he said the upcoming global trial will try to show how the drug seems to affect cognition.
While many in the United States were caught off guard by the approval, Cummings said it should perhaps not be surprising that companies elsewhere are making advances in Alzheimer’s.
“We are in a period of global innovation that we’re not quite used to,” he said. “This is a global disease and a challenge to the health and dignity of the elderly around the world.”
Cummings noted that some details of the clinical trial were presented at a scientific conference in 2018. He added: “We need to be open to these ideas at the same time as we need to hold them to a thorough level of scrutiny.”
Researchers focused on Alzheimer’s disease have expanded their approaches after years of focus on the so-called amyloid hypothesis, which asserted that the accumulation of a protein called beta amyloid in plaques in the brain caused the disease. Trials of drugs that cleared away those plaques have regularly failed to lead to any cognitive improvements in patients.
Last month, however, the drug maker Biogen announced that it was going to try to get Food and Drug Administration approval for an amyloid-clearing drug called aducanumab that it had previously said had failed in two trials. The company said a new analysis of some of the trial data showed a reduction in cognitive decline among some patients with early Alzheimer’s.