The search is on for cures to serious conditions such as cancer, heart disease, and neurological disorders. Treatments are critical for human health and for potentially cutting health care spending. But in areas such as Alzheimer's disease, which is projected to cost Medicare $189 billion in 2015, research progress is specifically thwarted by a lack of market incentives.
Currently 5 million people in the United States carry the diagnosis of Alzheimer's, and by 2050, 13.8 million Americans will have the disease. Some forms of Alzheimer's diseases stems from abnormal buildup of a normal chemical: clumps of beta-amyloid peptide (a type of protein) accumulate between cells in the brain and cause the brain to fail. This is often compared to the deposits of another normal chemical, cholesterol (a type of fat), that builds up in the walls of blood vessels, causing heart attacks that lead to heart failure.
With the assistance of new, breakthrough technology, we can now detect build-up of beta-amyloid clumps more than 20 years before Alzheimer's memory symptoms become evident, but, at present, there is no way to predict when or if clinical disease will develop. Nor is there any way to help people delay or prevent onset of symptoms in the way statins do for heart disease.
Recently, the hope that all forms of Alzheimer's disease begins with the buildup of amyloid has been shattered. About one-third of patients with clinically probable Alzheimer's have negative brain amyloid scans despite having obvious loss of brain substance and function on other types of brain scans. Experts are now proposing that Alzheimer's be divided into "amyloid-first" and "neurodegeneration-first" classes of disease.
Experts have long recognized that inflammation plays a role in Alzheimer's. This aspect of the disease has taken on new importance with the scrutiny of the genomes of nearly 75,000 Alzheimer's patients and with the application of computational methods to predict not only which molecules cause Alzheimer's but how those dysfunctional molecules are assembled into pathways. Our list of genes linked to common forms of Alzheimer's now numbers around two dozen. What is striking is how many inflammation genes are on the list. Taking the new imaging and genetic data into account, we must now set aside our simplistic notion that all Alzheimer's began with amyloid buildup. There are other ways for the pathology to begin even though we cannot yet tell at the bedside which pathway came first in any individual patient.
Any notion of conquering common forms of Alzheimer's within the foreseeable future is naïve. Recent estimates hold that the sequester has led to 25-30 percent reductions in the academic research workforce in just the past 5 years. Success is further stymied by the lengthy drug-testing process inherent in treating such slowly progressive diseases, and an unavoidable consequence of the long Alzheimer's drug-discovery process truncate the inventor's period of patent protection and market exclusivity, after which time, the drug faces generic competition. Companies and laboratories are pulling out of Alzheimer's because the odds are stacked against the chance that they will recoup their tremendous research investment. The newly recognized complexity of the disease is likely to hasten the exit of "big pharma" (i.e., the large pharmaceutical companies).
Setting aside for a moment the enormous emotional toll of Alzheimer's, the economics are potentially devastating to most countries where lifespan exceeds 80 years. Medicare spends $13,207 per year to care for a patient with Alzheimer's, and $4,454 per year to care for a similar patient who is not affected by the disease. If, by 2015, the onset of Alzheimer's were delayed by 5 years, this delay in disease onset would lead to a savings of $111 billion over 10 years. Without such a delay, Medicare spending for Alzheimer's will soar to over $1 trillion by 2050.
To lure companies and scientists back to Alzheimer's disease drug discovery research, we must rethink our regulatory protection policies. Thirty years ago, the Orphan Drug Act offered 12 years of market protection for the development of drugs that treat diseases that affect fewer than 200,000 Americans. The result was a 40-fold increase in FDA-approved orphan drugs.
More recently, the Biologics Price Competition and Innovation Act, tucked into the Affordable Care Act, granted biologics 12 years of market exclusivity, and already all major pharmaceutical companies and smaller biotech firms have large and growing biologic enterprises in many diseases, including Alzheimer's.
As of October, 2013, a decade has now passed since the fourth and most recent standard drug for Alzheimer's was approved, and none of the four slows disease progression. Alzheimer's typically begins with changes in memory, personality, or executive function, and eventually, all sentient brain function is destroyed. Patients die in what neurologists call a vegetative state.
An effective intervention to avoid or slow Alzheimer's progression would prevent incalculable human suffering and heartache, and save the nation billions of dollars in health care costs. Let's motivate medical research in this area by granting 12 years of market exclusivity. Until we do, generations of people will continue to watch helplessly as their loved ones leave them, one memory at a time.