Diana Zuckerman PhD, National Center for Health Research
Many pharmaceutical companies have tried to find a more effective treatment for Alzheimer’s disease and other types of dementia. So far, they have failed. This article is based on a study we published in the prestigious medical journal BMJ in 2015, which shows what happened when new drugs for Alzheimer’s were studied to evaluate their impact on biological “markers” instead of their benefits for patients, such as improving memory and cognition.
We selected for analysis all the promising Alzheimer’s drugs reviewed by the FDA within the previous five years for which a decision had been made of whether or not to approve the drugs.
All three drugs had impressive results in preliminary clinical trials. Two of the drugs showed great improvement based on the well-established biomarker of beta amyloid plaques on the brain, and the third showed improvement based on tests of memory and cognition. However, when larger, better designed clinical trials were conducted, two of the Alzheimer’s drugs were found to be ineffective, and the third drug caused an increase in memory problems and an increase in skin cancer.
Since the cognitive abilities of patients with Alzheimer’s disease tend to worsen over time regardless of treatment, it would be virtually impossible for physicians to realize that one of these drugs (semagacestat) was causing cognitive decline or that the other drugs were ineffective. Physicians would also have been unlikely to notice that semagacestat increased patients’ risk of skin cancer. It would not have been until years after these drugs were on the market that post-market studies would have been completed showing that the drugs were ineffective and possibly harmful.
Meanwhile, what would the approval of these drugs cost patients and other U.S. taxpayers? More than five million patients in the U.S. have Alzheimer’s disease, about 1.3 million of whom are being treated with an Alzheimer’s drug. We conservatively estimated that a newly approved Alzheimer’s drug would garner 18% of market share during its first year on the U.S. market based on biomarke qr data. That would translate to 234,000 patients a year taking a drug that put them at risk of a greater loss of cognitive skills than if they had taken a drug already on the market, or perhaps no treatment at all. If semagacestat was the drug approved, almost 19,000 more patients would have developed skin cancer, based on the phase III results.
Most current Alzheimer’s drugs are available as generics, which has reduced their price. At the time of our study, donepezil had most of the U.S. market share. The brand name version (Aricept) cost about $7500 a year at Walgreens, the largest pharmacy chain in the US. The brand name versions of memantine, galantamine, rivastigmine, and memantine-donepezil each cost over $5000 a year at Walgreens.
New drugs are priced based on the current market price of competing drugs, not on research and development costs. A very conservative estimate is that a promising new Alzheimer’s drug would be priced similarly to Aricept ($7,500 a year). This is 87% more than generic donepezil, almost doubling the cost for any patient who switched to the new drug.
Assuming 18% of the market share before postmarket studies are completed, we estimate the cost of treating 234,000 patients at $1.76 billion a year, or $7 billion over four years, which is the earliest that postmarket studies would be completed. Since current Alzheimer’s drugs are not very effective, direct-to-consumer advertising of a new Alzheimer’s drug would probably result in many more prescriptions, so the cost to patients and to Medicare could easily double.
Why should this matter to you?
Under pressure from Congress and industry, FDA standards have loosened in recent years, and the agency often approves products based on biomarkers that have good but inconclusive evidence of clinical benefit. For example, cancer drugs are often approved based on tumor shrinkage or progression-free survival and studies conducted after the drugs are in widespread use have shown that many do not help patients live longer. Osteoporosis drugs have been approved based on bone mineral density or microscopic bone fractures, rather than hip fractures that harm health.
If Alzheimer’s drugs are held to similarly low standards, patients will be the ones to pay, in terms of drug costs and less ability to function.
Read our published article here.
BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h6122 (Published 23 November 2015) Cite as: BMJ 2015;351:h6122