GAP President John Dwyer spoke about the Green Valley clinical trial’s success in China, which is now being tested in North America.
A new drug extracted from seaweed and inspired by traditional Chinese medicine has come to the United States, where researchers hope it will provide the breakthrough in Alzheimer’s treatment that has eluded us for nearly two decades.
The drug — oligomannate — has an imposing name but a humble origin. Its active ingredient is drawn from brown algae and evidence suggests that it can reduce inflammation in the brain in a way that benefits people with mild to moderate Alzheimer’s disease.
The drug was discovered in China, and promising studies there persuaded the Chinese equivalent of the FDA to approve the drug for Alzheimer’s patients in that country, as long as further research continues to show the drug is safe and effective.
Dr. Michelle Papka hopes that it will. “The exciting thing about this drug is that it takes a different approach than what we’ve seen in the past,” she says. “It’s an intervention that is derived from seaweed, so it really can be considered holistic, and people tend to favor that.”
Dr. Papka, director of The Cognitive and Research Center of New Jersey in Springfield, is one of some 200 researchers taking part in a Phase 3 clinical trial in the United States, Europe and Asia.
She’s looking for adults between the ages of 50 and 85 who have mild or moderate Alzheimer’s disease. The people chosen for the study will take the drug in the form of a pill for 12 months, or receive a placebo. At the end of a year, all participants will enter an “open-label” phase where they receive the drug for an additional six months, regardless of whether they took the drug or the placebo initially.
The question is, will this large, international study involving more than 2,000 Alzheimer’s patients bring a result convincing enough for the drug to be approved by the FDA here in the United States?
The fact that it’s already approved in China lends optimism to that.
“It is a differentiator in this study,” says John R Dwyer Jr., president of the Global Alzheimer’s Platform Foundation. “Here you have a drug that after careful evaluation by the Chinese FDA was approved for use in a population that represents roughly one-third of all the Alzheimer’s patients in the world. You’ve got an approved therapy being dispensed in China and now it’s appropriately being brought to other nations (for study).”
The drug, also known as GV-971, was discovered by Meiyu Geng of the Shanghai Institute of Materia Medica, a center that specializes in research in traditional Chinese medicine.
In the world of Alzheimer’s, it represents a dramatically different approach.
Most Alzheimer’s research over the past 20 years has focused on drugs that target the beta-amyloid “plaque” that accumulates in the brain of people with the disease. While years of effort have failed to bring a new drug to market, many researchers continue to see the “amyloid theory” as a viable approach. But at the same time, there’s a growing consensus around the need to consider new, unconventional approaches.
The Chinese drug GV-971 fits that description. It doesn’t target amyloid. In fact, it doesn’t even target the brain directly.
Instead, it goes after Alzheimer’s by way of the gut.
The drug targets an imbalance of microorganisms in the gutbiome that are thought to produce immune cells that eventually reach the brain and feed the inflammation associated with Alzheimer’s.
There are two reasons this roundabout approach makes sense for the treatment of dementia. First, the connection between the brain and the gutbiome is so strong that some scientist now refer to the gut as our “second brain.”
And inflammation is increasingly being looked at as a culprit in the progression of Alzheimer’s, alongside the plaques and “tangles” — which refers to tau protein. Amyloid and tau traditionally have been viewed as the hallmarks of the disease.
“First come the plaques, and then come the tangles, but then comes the third ingredient of neuro-inflammation,” says Dr. Papka. “The neuroinflammation piece seems to be where people can take a much more active role in trying to change their trajectory.”
That’s what studies done in China have suggested about the GV-971 drug. Successful early studies done on mice led to Phase 2 and Phase 3 trials in humans. Along the way, a Shanghai-based biotech startup called Green Valley Pharmaceutical acquired the drug and has been driving the research effort.
Dr. Sarah Lu, president of global development for Green Valley, says this medication reflects the company’s interest in bringing traditional Chinese medicine to bear on diseases such as Alzheimer’s.
“We believe in the holistic approach,” she says. “Our company has more of an emphasis on the use of natural materials and taking advantage of thousands of years of history.”
These days, Green Valley is making history of its own. In 2019, it announced that a shorter-term study involving 818 patients with mild or moderate Alzheimer’s found those who took the drug showed “solid and consistent cognition improvement.”
That led to the approval of the drug in China and the new, more ambitious clinical trial that patients are being recruited for here in New Jersey and elsewhere.
There has not been an Alzheimer’s research breakthrough in the U.S. since 2003 and the handful of drugs currently available do not prevent the disease or stop it from progressing. They only ease some of the symptoms of Alzheimer’s, and they only do that temporarily.
Dr. Papka says the current Green Valley trial seeks to add convincingly to evidence in favor of the drug. “And also to get more data on the biomarkers of Alzheimer’s disease,” she says.
The study will look at changes in brain volume, as measured by brain MRIs, and participants also will be assessed for changes in cognition, behavior and functioning.
“In China, over the course of 36 weeks, there was an improvement in cognition in people given the drug compared to people given the placebo,” Dr. Papka says.
That research effort here in the U.S. has the active support of the Global Alzheimer’s Platform Foundation, a network of leading research centers formed in 2016 to speed up the discovery of Alzheimer’s treatments by modernizing and streamlining the research process and reducing the cost of clinical trials. The Cognitive and Research Center of NJ is one of three GAP partners in New Jersey.
Dwyer, a co-founder of GAP, says the organization is agnostic about the potential treatments it supports. “We don’t pick winners and losers,” he says. “We’ll work with any science-based sponsor that wants to amp up their study.”
Still, the innovative aspects of this drug, involving a natural ingredient that attacks inflammation by way of the intestinal tract, has created a buzz in Alzheimer’s research.
“It’s well understood that the gut has a direct pathway neurologically speaking to the brain,” Dwyer says. “It should come as no surprise there’s a potential to mitigate brain pathology using the gut and inflammation. I think these are terrific studies.”
One day, GV-971 may take its place alongside donepezil and memantine, two of the drugs currently prescribed to Alzheimer’s patients. But for now, the drug must be studied on its own merits.
In the Green Valley clinical trial, patients can only enroll if they are not currently taking drugs like donepezil, which represents a potential obstacle to recruiting participants.
“It’s for people who are more newly diagnosed or have opted out of medications, or can wash out of the medications,” Dr. Papka says. “That’s a little more challenging because the standard of care is to put people on donepezil and later on they may end up getting memantine. Doctors don’t necessarily want their patients to come off those medications.”
Dwyer agrees that is “absolutely an issue,” but says these other drugs — referred to as cholinesterase inhibitors — have to be taken out of the equation in order to measure the effectiveness of GV-971.
He says a number of Alzheimer’s patients aren’t able to take these other drugs because of the strong side effects, so that could make them better candidates for the Green Valley drug, which has been shown to be both safe and well-tolerated.
Some people may also be willing to postpone taking the traditional Alzheimer’s drugs in favor of trying a promising new treatment, he says.
Researchers have to be “very careful” to discuss the pros and cons, Dwyer says. “It will be slow to ethically and carefully enroll people,” he says, “but there are choices to be made, and appropriate decisions can be arrived at.”
If you are interested in being considered for the study or learning more about it or other clinical trials you might be eligible for, you can call The Cognitive and Research Center of NJ at (973) 850-4622 or visit its website at: https://thecrcnj.com/do-i-qualify/
Green Valley hopes to conclude the current study in time to secure approval to make the drug available to Alzheimer’s patients in the U.S. by 2025.
In the field of Alzheimer’s research, that date has a special significance. Dating back to the presidency of Barack Obama, the U.S. government has pursued a national policy of developing the first effective treatments for Alzheimer’s by the year 2025.
The discovery of a new Alzheimer’s drug would be a landmark event, and the potential of that is not lost on Green Valley Pharmaceutical or the researchers currently working on the drug.
Dr. Lu says the approval of GV-971 in China created a sensation there. “People were quite excited; it got a lot of publicity from the media,” she says. “At the time when the drug was approved, they even made a postage stamp.”
Now, the focus is on delivering the additional scientific evidence needed to make that medication available to the rest of the world.
“Because there have been so many failed Alzheimer’s trials, and with the aging population, there is significant need,” Dr. Lu says.
“We want to work together to have a successful clinical trial,” she says. “Hopefully we can be part of helping reach that goal by 2025. We are hoping we can bring a new medication to Alzheimer’s disease patients in the U.S. and other countries.”
Originally posted by NJ.com on March 1, 2021.