Potential new Alzheimer's drug inspires optimism

CAUTIOUSLY OPTIMISTIC: A U.S. Centers for Disease Control and Prevention photo illustration of a couple dealing with Alzheimer's. Photo courtesy of CDC

Some of the nation's top neuroscientists responded with cautious optimism to a detailed presentation Thursday from pharmaceutical company Biogen about an experimental drug that appears to slow the brain's deterioration in the early stages of Alzheimer's disease.

Despite conflicting data from two identical studies, Biogen said the drug, known as aducanumab, appears to reduce the buildup of a key substance associated with the onset of dementia. On Thursday, the company offered the scientific community a more detailed and complete look at the data during a live-streamed presentation at the Clinical Trials on Alzheimer's Disease conference in San Diego.

Scott Turner, director of Georgetown University's Memory Disorders Program, which partnered in the study, said the presentation made a good case that the drug offers the best hope for the first significant treatment for the disease since 2003, when the Food and Drug Administration approved memantine, which is commonly marketed as Namenda and relieves some of the symptoms of dementia.

"The aducanumab results presented today are truly exciting and represent a major breakthrough in the treatment of Alzheimer's disease," Turner said in an email. "This study proves that we are on the right track to developing more effective, disease-modifying treatments designed to stop or slow memory decline in the earliest disease stage – when patients are still relatively independent in their daily functions."

Biogen has said it plans to seek FDA approval early next year. If approved, the drug would become the first to treat the underlying pathology of the dementia-causing disease.

The announcement comes about two months after the pharmaceutical company announced that after taking a second look at data from one of its studies deemed to have been a failure – and hearing anecdotal experience from study participants and their caregivers – the drug had shown evidence of effectiveness.

The drug appears to allow people in the early stages of Alzheimer's disease to continue independently going about their daily business longer than people who didn't take it. By one standardized measure of such functioning, the drug appears to slow the rate of deterioration by 40%, the study found.

"We're talking about people at a mild stage of disease still being able to work, bank, shop, travel, enjoy leisure activities for longer," said Sharon Cohen, a physician who heads the Toronto Memory Program. "And I submit to you that this matters more a lot more to our patients than what score they get on a memory test," added Cohen, who served on the panel for Biogen's presentation.

But others in the scientific community urged caution, saying Biogen's slicing and dicing of trial results could introduce bias and make the results seem better than they are. The company's stock also seesawed before ending up 3.4% at the close of trading. "At best, Biogen made a case for running a new clean trial to test its dosing hypothesis, not for putting this drug on the market," a Bloomberg Opinion biotech columnist wrote.

The Alzheimer's Association estimates that nearly 6 million Americans are living with the dementia-causing disease, a number that's certain to grow as the nation's demographics shift toward an older population. So is the cost, which has been estimated at $290 billion this year. By 2050, nearly 14 million people will have Alzheimer's and the costs could reach $1.1 trillion a year, the association says.

There are drugs on the market that alleviate some of the symptoms of Alzheimer's disease, such as memantine and donepezil, which is commonly sold as Aricept and treats symptoms of memory loss. But until now, Biogen says, no one has found a drug that attacks the underlying problem.

"We feel it's an important moment of the Alzheimer's field," said Maria Carrillo, the Alzheimer Association's chief science officer. ". . . It's not for us to determine whether that re-analysis with more complete data is going to be worth approval or not, because that's an FDA decision."

Aducanumab uses genetically engineered cells that mimic the natural disease-fighting processes in the body. The drug's monoclonal antibodies target amyloid beta, a protein whose accumulation in the brain is related to the onset of dementia.

Samantha Budd Haeberlein, Biogen's vice president of clinical development who explained the company's re-analysis, said the upshot was that the rate of deterioration for patients who were given consistently higher doses was slower than those given lower doses over time or placebos, as measured by cognitive tests and brain scans searching for biomarkers of the disease. The research also found that although side effects increased with the higher dosage – ranging from headaches and swelling in the brain to tiny hemorrhages - these also proved manageable with reductions in dosage.

But the drug's possible efficacy in attacking the disease only became apparent when the company re-examined the data after the studies were interrupted in March. At the time, one of the studies, named Emerge, was trending positive but the other, known as Engage, was not.

Owing to a midway change toward higher dosages that applied to both studies – and a difference in timing between each study's start – the researchers discovered some patients from the nonperforming study had indeed received the highest doses and the full number of treatments using the drug. By segregating that subset of data – but also taking precautions against introducing statistical bias – the researchers said they found evidence that the drug was actually working as hoped to remove beta amyloid plaque and slow the rate of deterioration in the brain.

"It's a plausible explanation for the positive study and the negative study," said Ronald Petersen, who directs the Mayo Clinic Alzheimer's Disease Research Center and the Mayo Clinic Study of Aging. Petersen, who consulted with Biogen on the results but did not participate in the study itself, said he was encouraged.

"The million-dollar question in the field has always been, 'So what?' If you remove plaque – the insoluble form of amyloid – at this stage of the disease, does it make any difference? Or is that sort of the tombstone of the disease?" Petersen said. "This seems to imply that removing the amyloid even at this stage can have a clinical impact."

Recommended for you