The pharmaceutical industry has not won FDA approval for a new drug to treat Alzheimer’s disease since 2003. But for the first time in more than a decade, there may be hope on the horizon. At the Alzheimer’s Association International Conference in Chicago on Wednesday (July 25), representatives from Biogen, a Cambridge-based pharmaceutical company, and it’s partner Eisai, a Japanese company, provided more details about a recent phase II clinical trial they had teased earlier this month. Though no group in the trial had seen significant improvement in the first year, after 18 months, the companies had observed more promising results. For the trial, a compound known as BAN2401 was given through an IV to six groups of adults with early stages of Alzheimer’s disease (five groups received various doses of the drug, and one received a placebo). BAN2401 works by reducing the chunks of amyloid buildup in the brain, which have long been thought to be one of the causes of brain degradation from Alzheimer’s. After 18 months, the 161 people receiving the highest dose of BAN2401 showed significant improvement both with the reduction of amyloid buildups and improved cognition compared to the placebo, according to STAT. There were a handful of instances of brain swelling as an adverse side effect, and some people experienced an allergic reaction where the IV was inserted. Although amyloid proteins have always been suspected to play a significant role in Alzheimer’s disease, this study is only the second to find a concrete connection between reduced amyloid buildups and improved cognitive function. It suggests that targeting these proteins may be a good way to combat the disease in future trials. Amyloid proteins were reduced by as much as 93% in some trial participants, making 81% of participants in the successful group what researchers call “amyloid negative.” Although this doesn’t mean these patients were cured, it’s a big deal. Additionally, the team compared the cognitive decline of this group to those who received the placebo using multiple metrics. They found that participants taking the highest dose of BAN2401 performed 30% better on a new cognition test called ADCOMS than those taking the placebo. ADCOMS is not the typical scale used to assess cognitive decline, but has been shown to be more sensitive (paywall) to changes in cognitive ability. When the group used a more common, longer-standing scale, participants in the highest dosage group performed 47% better than the placebo. It’s not clear how long the road to FDA approval for BAN2401 is. Although the results are promising, this trial was fairly small, and as Vox points out, it’s frowned upon in the research community to change your end results midway through a trial. At the moment, the FDA requires new drugs targeting Alzheimer’s to go through two phase III trials, showing a reduction of both a biological marker for the disease and cognitive decline. In March of this year, the organization published a draft report that said in the future they would accept only a reduction of biomarkers, without a reduction in cognitive decline, a decision has been supported by the research community. This is because in early cases of Alzheimer’s, patients may have the biological indicators of the disease without actually showing symptoms. Lynn Kramer, the chief medical officer for neurology at Eisai, said that the company and its partner plan to ask the FDA to accelerate BAN2401’s approval, based on these new phase II trial results.<doc-sep>There's been one glaring absence on the list of pharmaceutical company breakthroughs in recent decades: a drug to treat Alzheimer’s Disease, the most common form of dementia that some experts believe could single-handedly bankrupt Medicare in a matter of decades. As cancer drugs going through clinical trials have reached a 20 percent success rate, the search for a drug to treat dementia has been one of modern medicine's greatest frustrations: a 99.6 percent failure rate. Amyloid plaques accumulate outside neurons. Amyloid plaques are characteristic features of Alzheimer's disease. They lead to a degeneration of the affected neurons. Getty Images That long history of false starts helps to explain why positive clinical trial results for a new Alzheimer’s drug reported on Thursday by Biogen and Tokyo-based Eisai sent sent shares of Biogen soaring. The companies reported “statistically significant” evidence that the drug, BAN2401, an antibody targeting the beta amyloid protein, can slow progression of the deadly disease. Investors are predicting the final drug has a 50 percent chance of getting approved, Salim Syed, Mizuho Securities analyst, told CNBC on Friday. But Biogen officials were more cautious in their optimism, and for good reason. The beta amyloid protein has long been hypothesized as the primary cause of Alzheimer’s, and as a result, the target of a majority of drug trials. But failure has been so relentless that some dementia experts have questioned the drug industry's narrow focus on amyloid. Some focus has shifted to the tau protein. BAN2401 is the first late-stage, anti-amyloid antibody to achieve statistically significant results at 18 months, Biogen reported. Slowing cognitive decline, rather than stopping or reversing it, is still progress “Extremely encouraging” said Biogen chairman Stelios Papadopoulos to CNBC's Closing Bell on Friday. It's the first time a drug has shown the ability to clear the amyloid plaque, and “more importantly ... that the clearance of plaque was associated with a slowdown of the cognitive decline,” he said. But Papadopoulos said more still needs to be done: “It’s not as if we improved the condition or we stabilized even the cognitive decline. We’ve slowed down the cognitive decline.” Biogen’s drug trial re-tested at 18 months after it was originally deemed unsuccessful after 12 months. This time, the 856 patients in the trial “demonstrated a statistically significant slowing of disease progression” compared to those taking a placebo. “I’m cautiously optimistic,” The Mayo Clinic’s Ronald Petersen, who directs its Alzheimer’s Disease Research Center, told CNBC's Power Lunch.<doc-sep>Alzheimer’s is one of the deadliest, costliest, and most emotionally draining diseases in this country. Yet we have no drugs to reverse the condition, and the last medicine that came on the market to treat Alzheimer’s symptoms was approved some 15 years ago. So it’s no surprise that Alzheimer’s researchers, patients, and investors were eagerly anticipating the results of a phase 2 study on a potentially promising new medication, called BAN2401, from the drugmakers Biogen and Eisai. On July 5, the companies released a summary of the findings from a trial of the drug involving 856 patients with early Alzheimer’s, showing the medication could slow the progression of the brain-ravaging illness. On Wednesday afternoon, they presented more details about their findings at the Alzheimer’s Association International Conference in Chicago. The results have sparked cautious optimism. “Millions of people have Alzheimer’s, and right now it’s a death sentence. So any time we see positive results from a trial that appears to show disease modification, that gives us hope,” said Keith Fargo, director of scientific programs at the Alzheimer’s Association. “But it’s a cautious hope.” That’s because, while the experimental drug is potentially exciting, and may represent a step forward in the grinding, frustrating quest to treat Alzheimer’s, it’s far from being ready to prescribe to patients. First, the results haven’t been peer-reviewed, much less replicated by other researchers. Also, the way the drug companies ran and analyzed the data in their trial makes some experts suspicious. That’s why, with a huge market for an effective drug and massive potential profits at stake, we need to evaluate the new drug very, very carefully. The drug slowed Alzheimer’s progression by 30 percent, according to the drug company Before we explore why there’s reason to question the early results, let’s briefly touch on why they may potentially be significant. First off, Alzheimer’s is an extremely complex disease of the brain. It’s not caused by a single cell failure. Instead, the best scientific understanding of what’s likely going on with Alzheimer’s is called the “amyloid hypothesis.” Beta-amyloid is a protein in the brain, and when it’s metabolized abnormally, it sets off a cascade of events that eventually kills the nerve cells in the brain and causes the brain to shrink. Years (or even decades) after this process begins, people start to experience the hallmark symptoms of Alzheimer’s, like forgetfulness and confusion. Despite the fact that Alzheimer’s is the most common cause of dementia in older people — and there are an estimated 5.7 million Americans living with the disease — there is not a single drug available to treat the condition. (The medications on offer only ameliorate Alzheimer’s symptoms — like anxiety, aggression, and depression — and only in some people.) The path to finding a drug that would stop the progression of or reverse the disease has been littered with failures. And that’s largely because of how complicated Alzheimer’s is. “It’s a complex system failure — multiple areas of the brain that depend on each other fail,” said Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center. So despite spending billions of dollars on research into a variety of therapeutic approaches, there have been no new drugs in 15 years. And while amyloid buildup is necessary to diagnose the disease, there are many potential contributors to Alzheimer’s — including genetics or a history of head injury or stroke. The new, experimental medicine, BAN2401, purports to test the aforementioned amyloid hypothesis. When amyloid protein is misprocessed, it begins to accumulate in the brain, forming a sticky buildup outside the nerve cells called beta-amyloid plaques. The accumulation of amyloid also stimulates an immune response, which causes another set of proteins (the tau proteins) to form tangles inside the nerve cells. BAN2401, which is delivered intravenously, is an antibody that helps the immune system fight that disease process. “The theory is if we can interrupt the plaque formation, and these toxic forms of amyloid, hopefully we can interrupt that whole process and slow down memory loss — and that’s why we’re excited about this finding,” said Stephen Salloway, the director of neurology and the memory and aging program at Butler Hospital in Providence, Rhode Island, and a professor of neurology at Brown University. (He wasn’t involved in the trial but also runs clinical trials for Biogen.) In the placebo-controlled, double-blind, randomized study of 856 patients with early Alzheimer’s, the drug companies said brain scans showed that higher doses of the medication were able to reduce amyloid plaques after 18 months. They also used an Alzheimer’s scale (called ADCOMS) to measure clinical symptoms in the patients, and found that the reduction in plaques corresponded with a slowing of Alzheimer’s disease progression by 30 percent. The most common side effect was allergic reaction at the site of infusion, and some patients experienced brain swelling. “We think this result is really the first of its kind,” Lynn Kramer, chief medical officer of Eisai’s neurology business group, said in a press briefing Wednesday, and “robust enough to approach regulatory authorities to discuss next steps.” If the results are indeed solid, and the drug is approved for market, it could mean people with early-stage Alzheimer’s might be able to keep the disease at bay. It could also mean that we finally have an actual treatment for the disease, and not just its symptoms, available for patients. The drug still needs to pass a phase 3 clinical study and FDA scrutiny But again, there’s reason to be cautious with these findings. Today’s data, unfortunately, can’t definitively answer the question of whether this is truly an Alzheimer’s breakthrough. First, the trial was a phase 2 study, and the drug will likely need to pass a phase 3 trial, involving a larger group of people to confirm its effectiveness and monitor any side effects before it can be approved by the Food and Drug Administration. “We want to make sure the data are meaningful and reproducible, and I think doing another trial to be able to reproduce the results would make good sense,” Salloway said. The results are still preliminary and not yet peer-reviewed or published.<doc-sep>The long, discouraging quest for a medication that works to treat Alzheimer’s reached a potentially promising milestone on Wednesday. For the first time in a large clinical trial, a drug was able to both reduce the plaques in the brains of patients and slow the progression of dementia. More extensive trials will be needed to know if the new drug is truly effective, but if the results, presented Wednesday at the Alzheimer’s Association International Conference in Chicago, are borne out, the drug may be the first to successfully attack both the brain changes and the symptoms of Alzheimer’s. “This trial shows you can both clear plaque and change cognition,” said Dr. Reisa Sperling, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital in Boston, who was not involved in the study. “I don’t know that we’ve hit a home run yet. It’s important not to over-conclude on the data. But as a proof of concept, I feel like this is very encouraging.” Aside from a couple of medications that can slow memory decline for a few months, there is no effective treatment for Alzheimer’s, which affects about 44 million people worldwide, including 5.5 million Americans. It is estimated that those numbers will triple by 2050.<doc-sep>
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. 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. To find out more, 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. 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," the Alzheimer’s Association said in a statement. When trials don't meet their primary endpoints — when they don't do what they were designed to do — that can shed doubt on any results. And depending on which test results were used, the improvement was either 30 percent or 47 percent - a discrepancy that troubles some experts. But anything that might help would be welcome. “The global urgency to better treat and prevent Alzheimer’s disease and other dementias is higher than ever, and growing," the Alzheimer's Association said.