August 23, 2010
Last week’s disappointing news that another Alzheimer’s disease drug failed in late stage clinical trials raises an important question for policymakers: What’s Plan B?
The primary strategy of the nation’s scientific establishment, both public and private, to curb the devastating social and personal costs of the disease is to pour billions of dollars into the hunt for drugs that can slow or prevent dementia’s onset. That strategy has so far come up empty.
Eli Lilly’s drug, Semagacestat, which was designed to inhibit the buildup of amyloid beta (a-beta), a complex plaque in the brains of people with mild cognitive impairment, was only the latest in a lengthening string of failed drug candidates that promised to delay onset of full blown dementia. Not only did more people advance to Alzheimer’s on the drug compared to those on placebo, more developed debilitating side effects. In the past two years, Pfizer, Myriad Genetics and several other firms have also reported disappointing results with drugs aimed at a-beta-related targets.
Though the final results for clinical trials using expensive biotech drugs to reduce a-beta are still several years away, some researchers are beginning to question the entire thesis. The venture capital industry is already voting with its dollars. According to Windhover Information, start-up biotech firms engaged in Alzheimer’s disease research received just $36 million in venture capital funding in first half of 2010, when the economy recovery was getting underway, compared to $105 million in 2008 and $153 million in 2009, when the nation was mired in recession.
With 77 million baby boomers about to enter their
declining years, the number of people with
dementia is expected to triple by 2050.
National Institutes of Health-funded researchers who are working closely with the private sector are now focused on identifying alternative strategies for inhibiting the disease. The Alzheimer’s Disease Neuroimaging Initiative, a $93 million program that is nearly one-third funded by industry, is seeking to identify other proteins that either increase or decrease in the brains of people with early symptoms of cognitive decline. These biomarkers of the disease would then serve as alternative drug targets.
“Is a-beta the right target? Are the drugs being tested too late in the disease process?” asked John Q. Trojanowski, an Alzheimer’s researcher at the University of Pennsylvania. “That’s why we have to push forward with (other) biomarkers. Most drugs in development are a-beta focused. We need to not put all our eggs in one basket.”
One Year: $172 Billion
But finding and validating another target for drug development may take years, if not decades. Coming up with drugs for conditions like Alzheimer’s for which there is no known therapy is like a scientific crap shoot. Billions of dollars can be poured into theories that in the end prove to be no more effective than laetrile for cancer.
That’s why many researchers are encouraging the government to take a second look at developing alternative care strategies that can lower the cost of treating Alzheimer’s patients in the near term. The stakes for the health care system are enormous. Alzheimer’s disease affected 5.3 million older Americans in 2009 and burdened the health care system with $172 billion in direct costs, mostly paid for by Medicare and Medicaid (that excludes the toll, both financial and psychological, on direct caregivers, who are usually family members). With 77 million baby boomers about to enter their declining years, the number of people with dementia is expected to triple by 2050.
One program proven to lower health care costs in small but well-controlled clinical trials was conducted in New York City, with its first results published nearly 20 years ago. It provided counseling and social support for caregivers, usually the spouses and family members of the person with dementia. The family members participated in six sessions, where they learned about the stages of the disease. The caregivers enrolled in support groups. They were given a 24-hour hotline to call during acute crises, such as when the Alzheimer’s patient became angry, violent or ran away.
“We demonstrated that caregivers were less depressed, their physical health is better, and they were under less stress,” said Mary Mittelman, director of psychosocial research and support at the Center of Excellence on Brain Aging at New York University. That, of course, reduced direct health care costs for the caregiver, who was usually on Medicare him- or herself.
“But from the fiscal perspective, the most important result was that compared to usual care, this intervention kept people with dementia out of nursing home care for 557 days on average,” she said. “That’s a year and a half, or over $100,000, in nursing home costs. That’s a huge cost saving.”
The results of the experiment only recently caught the government’s eye. It has funded broader demonstration projects in California, Georgia and Minnesota, she said.
Medicare is still reluctant to pay for such counseling on a national basis. “Caregiving is not an illness,” said Mittelman. “Ideally, you want it to be paid for as part of the care of the person with dementia.”
Another project, organized by researchers at Duke University, is focusing on caregivers in rural and minority families with Alzheimer’s patients living at home. Cost-saving data are not yet available, according to Elizabeth Gould, director of state programs for the Alzheimer’s Association, but if it replicates the New York study, it could represent significant cost savings for state Medicaid programs, which pick up most of the nursing home tab for low-income Alzheimer’s patients.
Lowering Long-Term Costs
The greater coordination of care enabled by the recently enacted Patient Protection and Affordable Care Act could also lower the long-term costs of treating Alzheimer’s patients. Many seniors have multiple chronic conditions like heart disease, diabetes and arthritis. A failure to detect the early stages of dementia — a time when many spouses and family members are in denial — increases the likelihood that seniors with deteriorating mental status will skip medications or treatments that prevent far more serious and costly complications later on.
The Center for Medicare and Medicaid Services (CMS) is considering a rule that would require (and reimburse) physicians to conduct cognitive impairment testing as part of Medicare beneficiaries’ annual wellness checkup. “A recent pilot project at the Veterans Administration, which used annual cognitive impairment testing followed by care planning and other services, found that health care costs fell by 30 percent compared to a similar population where such testing wasn’t provided,” said Robert Egge, vice president for public policy at the Alzheimer’s Association. The group is pushing legislation that would make follow-up care planning, caregiver counseling and other social support services part of the Medicare benefit package, in addition to the annual screen.
And then there’s risk factor reduction. While never proven in controlled clinical trials, association studies have shown that people are at increased risk of developing dementia if they are sedentary, poorly educated, smoke and don’t follow a heart-healthy diet. Even researchers like Trojanowski, who are working on developing new drugs, recognize that “while we’re waiting for the home run, there are other things the public should be aware of. We should be doing clinical trials to show whether people with mild cognitive impairment who follow healthier lifestyles delay the onset of Alzheimer’s,” he said.
Doubt on Tactic in Alzheimer’s Battle (New York Times)
'Biomarkers' Could Spot Alzheimer's Disease Early, Studies Suggest (Bloomberg)
Would You Take a Test to Predict Alzheimer's Disease? (ABC News)