Wednesday, July 25, 2018

New Experimental Drug Being Tested for Alzheimer’s Disease/Researchers Conclude Lowering Blood Pressure Reduces Mild Cognitive Impairment

“An experimental drug being tested to see if it can treat Alzheimer’s disease helped slow the inevitable loss of clear thinking and memory that comes with the condition, researchers reported Wednesday, [July 25, 2018].

“It’s a rare success in a field littered with failures. No drug has yet been shown to reverse the symptoms of Alzheimer’s, which affects more than 5 million Americans and has no cure. And this one is no home run. Everyone who took the drug continued to get worse. But those who got the highest doses got worse more slowly.

“‘We had a 47 percent reduction in decline at 18 months,’ Dr. Lynn Kramer, chief medical officer of the neurology division of drug company Eisai, told reporters. It was the second piece of good news on the Alzheimer’s front.

“Earlier Wednesday, researchers reported that lowering blood pressure to recommended levels was safe and reduced the rate of mild cognitive impairment — a precursor of dementia — by 20 percent.

“Eisai and its U.S. partner Biogen presented results to an eager audience at the Alzheimer’s Association annual meeting in Chicago Wednesday. They’ve been treating more than 800 patients with early-stage Alzheimer’s with various doses of the drug, called BAN2401. It’s a monoclonal antibody, a lab-engineered immune system protein designed to remove amyloid plaques from the brain.

“One leading theory about Alzheimer’s is that these amyloid clogs cause the disease. ‘This is the first large trial to support the amyloid hypothesis,’ Kramer said. The drug cleared the plaques from the brains of the patients, by 93 percent at the highest dose.

“Dr. James Hendrix, director of global science initiatives at the Alzheimer’s Association, says the findings are significant. ‘Not only do we see a slowing in the rate of cognitive decline, we also see that reduction of amyloid burden in the brain as measured by amyloid PET (imaging),’ Hendrix told NBC News. ‘That biomarker confirmation really adds confidence that what you are seeing in the primary measure is real.’

“Still, the researchers had to tweak the results to be able to declare a success. When the trial was at the 12-month point, they said, they didn’t see a benefit. Now, after their patients have been infused with the drug for 18 months, they say they can see an effect.

“Now, Hendrix said, the companies will have to design an advanced trial called a Phase 3 clinical trial — the final stage before seeking full Food and Drug Administration approval.20
“Dr. Howard Fillit, founding executive director of the Alzheimer’s Drug Discovery Foundation, supports the way Biogen and Eisai changed the study. ‘The Biogen studies are being done in a different way than all of the studies we have done for the past 40 years,’ Fillit, who was not involved in the research, told NBC News.

“‘The Biogen study took advantage of everything that we have learned about doing modern, efficient clinical trials.’ He called the results ‘amazing’ — especially the reduction of amyloid in the brain.

“It’s difficult to describe what a 47 percent decrease in in the worsening of symptoms looks like, researchers said. The patients all took a battery of tests used to diagnose and define Alzheimer’s. ‘When you are talking about early-stage Alzheimer’s disease, you are talking about people who are living pretty well and still able to live independently at home,’ Hendrix said. ‘If you are able to slow that decline, that means they may be able to keep that quality of life for more time.’

“One problem is a side effect that causes the brain to swell, which has been seen in all the monoclonal antibodies tried against Alzheimer’s. This affected about 10 percent of the patients. ‘This is the second Alzheimer’s clinical trial that has demonstrated both clearance of amyloid from the brain and cognitive benefits — again, the studies were not large enough to definitely demonstrate cognitive efficacy and the BAN2401 study did not meet its primary endpoint’ of 12 months, the Alzheimer’s Association said in a statement.

“‘The global urgency to better treat and prevent Alzheimer’s disease and other dementia is higher than ever, and growing.’ The group predicts that the number of people with Alzheimer’s will triple by 2050 unless someone finds a way to stop it” (NBC News).  

For More Articles on Alzheimer's Disease, Click Here. 


  1. A Critique from Intensive blood pressure control and ‘dementia’: another mad rush to report incomplete SPRINT findings:

    “…[A]lthough the Alzheimer’s Association news release DID provide detailed information about adverse consequences from aggressively lowering blood pressure, none of the news coverage we came across did so. We’ve encountered omissions like this before in our extensive coverage of the SPRINT study, whose findings were initially reported as a slam dunk that would immediately change practice. Only later did details emerge that would make many clinicians question the validity of the findings and their relevance to broad swaths of patients.

    “‘The original SPRINT trial generated a robust discussion amongst clinicians regarding how low is too low, especially for older patients,’ said Preeti Malani, MD, a professor of medicine at the University of Michigan.

    “‘The decisions regarding a blood pressure goal are very nuanced and individualized. While appropriate treatment of high blood pressure is one of the most important clinical interventions that can be made for patients, decreasing dementia risk is probably not what drives the calculus around lower blood pressure goals. So although the MCI data from this study may be encouraging, I’d like to see something more definitive before calling this an effective means to stave off dementia. That’s overstated based on this abstract.’

    “…Dozens of news stories have already been circulated but crucial details are missing. We recommend, at the very least, paying attention to the following:

    “Go beyond a single source — much of the coverage only quotes the lead author. Most often the quotes are glowing and not balanced by independent sources that ought to be used to confirm or refute findings.

    “Check the hyperbole — glowing quotes by lead authors are often major sources of unjustified or hyperbolic language. The lead author of this research was quoted by Bloomberg (above link) as saying this about aggressive blood pressure treatment: ‘It may give another five or 10 years with a healthy brain.’ That’s based on speculation, not data.

    “‘Preliminary & Unpublished’ — kudos to the Associated Press who had this to say about the study results: ‘They’re considered preliminary until published, expected later this year.’

    “Look beyond the meeting — …[T]here are often existing published studies available that address the same topic. Not infrequently, the findings may be quite different. Giving readers that information empowers them to better weigh harms and benefits.

    “There is something about embargoed news releases coming from medical meetings that triggers an unhelpful sense of urgency amongst healthcare reporters.

    “Very, very rarely do such abstracts contain breakthroughs, paradigm shifts, or unassailable information that will immediately change patient care. And even if they did, isn’t that exactly the kind of information reporters would want to take more time with?”

  2. One More Spoiler Alert:

    “…Why did this experimental drug — BAN2401 — attract an avalanche of news coverage?

    “…It’s a potentially market. But another explanation is less benign and hinges on the huge financial stakes, not just for the two companies developing this particular drug but for others working on similar plaque-busters as well as makers of PET scans that detect plaque and research institutions that are trying to find a way to arrest the disease.

    “‘I call it the Alzheimer’s industry complex,’ said contributor Susan Molchan, MD, who has written about the push to promote brain scans and drugs to diagnose and treat Alzheimer’s. ‘It’s a potentially huge market and that’s why these companies, despite all the decades of failures, persist.’

    “Molchan, a psychiatrist and former clinical researcher at the NIH, said while many medical experts quoted in news stories aren’t part of the BAN2401 research, they or their institutions may receive funding from companies that stand to profit if a new Alzheimer’s treatment wins FDA approval.

    “Everyone wants a drug that will provide meaningful benefits to patients, but danger lurks in the enormous incentives to make marginal drugs seem more beneficial than they really are. ‘There are other amyloid drugs out there. Once one gets approved, it will make it easier for others,’ Molchan said. This context often isn’t acknowledged in news stories about potential treatments…

    “Some news outlets did a particularly good job of conveying the limitations of the evidence. The Associated Press’s Hopes rise again for a drug to slow Alzheimer’s disease reported that the trial was ‘considered a flop’ because it didn’t meet its main goal, and further wrote: ‘There are lots of caveats about the work, which was led by company scientists rather than academic researchers and not reviewed by outside experts. The study also was too small to be definitive and the results need to be confirmed with more work, dementia experts said.’

    “…Meanwhile, the Wall Street Journal’s Alzheimer’s Drug Shows Benefit, But Some Experts Say More Testing Needed contained this critical reporting: ‘Using an older measure that is widely accepted in the Alzheimer’s disease research field, known as ADAS-COG, (drug maker) Eisai said the highest dose of the drug conferred 47% less decline in patients’ disease at 18 months, versus placebo. But with another older measure known as the clinical dementia rating, the 26% improvement wasn’t statistically significant, meaning it could have been due to chance.’

    “…Some did a better job than others at emphasizing that the drug failed to meet its primary endpoint, as mentioned in an Alzheimer’s Association news release. That’s disappointing because shifting the objective of a trial introduces the potential for researchers to create positive-sounding results by cherry-picking the outcome measures that they report. There could have been dozens of secondary outcomes that were tracked by researchers but not revealed to the public.

    “‘It’s important to say what you’re going to do beforehand to minimize bias. If you are making modifications in your protocol, which would include extending the study or your statistical analysis, it can get to the point where it can seem fudged and massaged,’ Molchan said.

    “Future news coverage should strive to examine the big picture of what will happen if one these amyloid-busting drugs does win approval. Specifically, how good are the benefits for individual patients, and what is the cost to society?

    “‘We don’t want a drug approved that has a big effect on amyloid but just squeaks by on the cognitive stuff, because it’s going to cost Medicare zillions of dollars between the drug and the scans, and most people with dementia have a number of processes going on,’ Molchan said.”