Re-Posted from STAT News
By George Vradenburg and Howard M. Fillit
“The time has come in America when the same kind of concerted effort that split the atom and took man to the moon should be turned toward conquering this dread disease.” That was President Nixon in his State of the Union address 48 years ago. The dread disease he was talking about was cancer, the second leading cause of death in the country, and he used the address to open his “war on cancer.”
Since then, we have made major strides against that disease. Death rates have been declining for 25 years. Breakthrough treatments and cures are now coming at breakneck speeds. But we have made little or no progress against another “dread disease” plaguing Americans — Alzheimer’s.
When President Trump delivers his State of the Union address tonight, he should declare war on Alzheimer’s.
Nearly 6 million Americans are currently living with Alzheimer’s. By 2050, nearly 14 million will have it. In addition to its physical and emotional toll, Alzheimer’s is also the most expensive disease in the U.S. It now costs the nation close to $300 billion a year; by 2050 it will surpass $1 trillion. In a recent survey, 86 percent of Americans said they view Alzheimer’s and other types of dementia as the biggest health issue facing our country over the next decade.
Other world leaders are waking up to the global scale of Alzheimer’s and taking action. In fact, the fight against it was on stage at the World Economic Forum last month.
It’s time for America to take the lead, otherwise we will be on the losing end.
There has been some progress, but not nearly enough. One year ago, for example, FDA Commissioner Scott Gottlieb described the “urgent need for new medical treatments” for Alzheimer’s, and announced important changes in the drug-testing process meant to speed new treatments to market. Among them was a modern approach to approving Alzheimer’s drugs that permits clinical trials to show effectiveness by improving either a patient’s cognition or function, but not requiring it to show both, as had long been the case.
A year later, though, not a single new Alzheimer’s drug has been able to meet the new standard and be approved.
Gottlieb had it right about the urgency. Since the last novel Alzheimer’s drug hit the market 16 years ago, deaths from Alzheimer’s have climbed more than 50 percent.
But he was understated when he suggested that progress against this disease, compared with others, “has been uneven.” Today, there are nearly 1,000 studies in the final phase of the clinical trial approval process in the United States, called Phase 3. But just 31 of them are for Alzheimer’s.
In Phase 3 trials, treatments that have shown promise in earlier trials are expanded to larger populations. It’s the stage at which drugs are tested for effectiveness; it’s also the final step before the FDA evaluates a drug for approval and market use. But Phase 3 trials are hugely expensive. The cost of a single Phase 3 clinical trial in Alzheimer’s exceeds $400 million, and it can take as many as four separate Phase 3 trials to receive FDA approval.
So the biggest challenge on the path to victory lies in the drug testing process. More specifically, the lack of sufficient treatments that make it to Phase 3. We need to change that trajectory.
The 68 Alzheimer’s drugs currently in Phase 2 trials have only some assurance that their pathway for development will be supported by a modernized FDA approach. Alzheimer’s, like cancer, requires drugs that target different aspects of the disease, from memory loss and behavioral changes to inflammation and vascular problems. So we need to move through the development and testing stages a larger volume of promising drugs that address multiple causes to effectively treat Alzheimer’s.
Here are five steps that will help us develop effective new drugs to fight Alzheimer’s disease.
First, the U.S. should establish a philanthropic “impact fund” directed at mid-stage clinical research that brings government, industry, and nonprofit entities together to end Alzheimer’s. The United Kingdom has already taken steps in this direction with its Dementia Discovery Fund that includes important seed money from the government. Such an impact fund in the U.S. would significantly boost the Alzheimer’s drug development process.
Second, Medicare and Medicaid, which today bear two-thirds of the economic burden of Alzheimer’s, could model the value of drugs to reduce the cost of Alzheimer’s for these federal and state programs. A drug that would improve outcomes and reduce the costs of care presents a case for investment in reducing or offsetting the drug’s price and assuring broad access — a demand for which may be unprecedented in our nation’s experience.
Third, the FDA’s new Office of Drug Evaluation Science should create incentives for industry to increase investments in larger Phase 2 clinical trials. It should consider approving drugs that meet safety and effectiveness standards and exhibit strong performance after Phase 2 and then follow the drug after approval for further careful tracking.
Fourth, many current Phase 2 clinical trials involve repurposed drugs that have already been approved and are on the market for other diseases but that appear to address new Alzheimer’s targets. These, too, should be accelerated for review and approval. This would more quickly transition potentially effective and safe repurposed drugs to the clinic by adjusting the threshold for what is considered a significant therapeutic effect.
Fifth, the FDA can incentivize the pharmaceutical and biotech industries by using more “breakthrough therapy” designations to speed approvals for Alzheimer’s drugs. To date, more than 120 cancer drugs have received this designation. Yet you can count on one hand the number of Alzheimer’s treatments that have received the breakthrough designation.
In each of these steps, the government will be making investments that result in new treatments, better health outcomes, and reduced costs. If we don’t change the way we do business, we will slow or stop potential Alzheimer’s treatments from ever reaching patients.
Our understanding of Alzheimer’s is stronger than ever before, and there are promising drugs in the clinical trials process that have the potential to become approved novel treatments.
President Trump has the opportunity to win the war against Alzheimer’s disease. But he needs to enlist the country to fight it.
George Vradenburg is the chairman of UsAgainstAlzheimer’s, which he co-founded in 2010, and a member of the World Dementia Council. Howard M. Fillit, M.D., is the founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation and a clinical professor of geriatric medicine and palliative care, medicine, and neuroscience at the Icahn School of Medicine at Mount Sinai. He reports having received payments for consulting from Axovant, Genentech, Merck Otsuka, RTI, Samus, and vTv.