Despite the devastating toll of Alzheimer’s disease on patients and families, and the potential for its costs to bankrupt the medical system, research into AD has been stymied. The last time a drug was specifically approved for AD was in 2003.
According to current projections, AD will overwhelm the national healthcare system by 2050, affecting 16 million Americans and costing Medicare and Medicaid $1.1 trillion. In the wake of numerous failed clinical trials over the past decade, several large pharmaceutical companies have shuttered their AD research programs, creating a sense of hopelessness.
At this rate, we might have to wait more than a century before we finally develop an effective treatment. An alternative is to take “multiple shots on goal,” developing many drugs in concurrent trials. Such an effort would exceed the budgets of even the largest pharmaceutical companies – but not that of the State of California.
But for the very reasons that Big Pharma has retreated, California has an opportunity to lead the effort to stop AD. Historically, the state has not hesitated to pursue grand challenges. With the organizational structure, financial clout, technological resources, biomedical expertise, and political will of the world’s fifth largest economy, California is the ideal venue for taking on AD.
The biggest need is covering the enormous cost of clinical trials, now upwards of $100 million per trial and growing, which is so expensive that only a few are conducted at any one time. At this rate, we might have to wait more than a century before we finally develop an effective treatment. An alternative is to take “multiple shots on goal,” developing many drugs in concurrent trials. Such an effort would exceed the budgets of even the largest pharmaceutical companies – but not that of the State of California.
California’s patient pool is unparalleled in its racial, ethnic and economic diversity, and the state is home to one of the largest AD databases, the Alzheimer’s Disease Neuroimaging Initiative, which collects and validates MRI and PET images, cognitive tests, cerebrospinal fluid and blood biomarkers, and genetic data to use as predictors of the disease.
The state is also home to the world’s most successful and advanced technology companies, many of which developed the algorithms responsible for teasing subtle patterns from oceans of data.
California has more than 12,000 life science establishments that generate an annual economic impact of $312 billion. In particular, the University of California health sciences programs are a part of the nation’s leading state university system.
According to the 2017 UC Accountability Report, UC began more than 3,000 clinical trials over the last five years, with more than 2,700 underway during 2015-16. Of the $2.5 billion UC received in that period in medical research awards, about 20 percent of the total was targeted for clinical trials, and 88 percent of these projects were sponsored by businesses.
And during 2015-16, UC medical centers managed nearly 4.9 million outpatient visits, which is the most common setting in which AD patients are seen. These numbers do not include the active relationships UC health programs maintain with more than one hundred affiliated Veterans Affairs facilities, or the county and community-based health facilities located in the nation’s most populous state.
What would a California-based approach to Alzheimer’s disease look like? It would first amass a stream of investigational drugs from UC research labs where the intellectual property for these discoveries is currently held.
These investigational compounds, and others from biotech start-ups and other universities, would advance through a California Alzheimer’s Solutions Consortium And Data Exchange (CASCADE) megafund, a new business and financial structure that would develop a network of Alzheimer’s expertise and a portfolio of compounds in much the same way that an investment fund might accelerate a portfolio of new companies.
This megafund would streamline the entry of these drugs into concurrent clinical trials through the UC system in exchange for a portion of their intellectual property, and provide follow-on financing as drug candidates progress.
One important service that CASCADE would provide is the validation of these compounds – confirming that they do what they’re supposed to do – so as to better define their role in treatment. Previous AD trials were hampered by the difficulty in directly measuring the effects of a potential drug on the brain, a crucial parameter for success.
Recent developments have greatly improved the validation of drug effects within the brain, such as brain imaging of AD pathology and biofluid measurement of drug engagement with the disease target. Besides providing greater safety for patients, such measures would allow drug candidates to be better prioritized.
These studies would be conducted within the UC healthcare system, with CASCADE’s support, providing an incentive for individual holders of investigational intellectual property to participate. Uniform standards would lower the risk of failure for new compounds.
Most investigational drugs die in the middle ground of the development process. CASCADE will select multiple investigational drugs from a prioritized portfolio to bring to the entry point of a phase 3 trial.
Clearing the runway to phase 3 will be a standing cohort of subjects within the UC health system, the use of an adaptive platform trial design similar to the innovative I-SPY breast cancer trials pioneered by UCSF, and other innovative features to speed the process.
California’s intellectual, financial, and political resources could power a scientific juggernaut, leading to a treatment or cure for one of the biggest scourges of the 21st century. By front-loading the costs of the research through a CASCADE megafund that compresses the drug discovery process into an efficient machine, the financial reward for the state should also be historic.
The return on California’s investment could exceed every other industry in the state – truly a case of “doing well by doing good.”
Kenneth S. Kosik, M.D., is co-director of the Neuroscience Research Institute at UC Santa Barbara. Andrew Lo directs MIT’s Laboratory for Financial Engineering. Reach them at firstname.lastname@example.org and email@example.com.