In a slew of recent flashy endeavors, scientists, academics and exceptionally rich people have taken on the aging process. In 2013, Google launched Calico, its billion-dollar anti-aging research and development arm, which the following year formed a partnership with pharmaceutical giant AbbVie. Meanwhile, another major drug company, Novartis, is developing a patentable form of rapamycin—a biological agent discovered in the soil on Easter Island—which has been shown to boost immune function, and the company hopes it could become the first viable anti-aging pill.
But, according to Dr. Nir Barzilai, a scientist based in the Albert Einstein College of Medicine in New York City’s Bronx borough, we might already have the drug we need to slow the aging process—and it’s dirt cheap. Metformin is an old, generic diabetes drug, known for its blood sugar–lowering properties and for being quite safe. It’s common, and it costs about 35 cents per pill. It has also been found to stall the aging process in animal studies.
In June, Barzilai, along with academics from the not-for-profit American Federation for Aging Research (AFAR), approached the Food and Drug Administration with an idea: the Targeting Aging With Metformin (TAME) study, to see if metformin could do for humans what it does for animals. It would be the first clinical trial to test if a drug could slow human aging. The FDA said yes, and since that June meeting the media has exploded with excitement over the purported “fountain of youth” drug, with rumors that it could extend human life span up to 120 years.
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The problem, though, is that no one has agreed to front the capital required to get TAME off the ground. That’s not surprising: There are plenty of reasons Big Pharma won’t fund a study that would make a cheaply available, common drug the must-have for the 21st century. Pharmaceutical companies spend big money on drug research and development to bring products to market because they get several years of exclusive marketing rights for any new drug. This guaranteed temporary monopoly in the drug market can be a massive windfall. A pharma company could test generic metformin in clinical trials, get it approved and market it for something other than diabetes—and that company would be the only one allowed to do so during the patent period. Companies repurpose drugs all the time. Colesevelam, for instance, was developed by GelTex to reduce cholesterol, and later it was repurposed by Daiichi Sankyo to treat patients with Type 2 diabetes.
For that to happen, though, the FDA would have to do something it’s never done: approve an anti-aging indication for a drug. In large part, that’s because there’s little agreement in the scientific community on what biomarkers—measurable biological cues indicative of a certain condition—are quantifiably associated with aging. And the idea of testing a drug to see if it helps lower risk for a battery of ailments directly conflicts the standard model that clinical trials have followed for years: one drug, one disease.
That’s why, to some extent, what matters most about TAME is not that it proves metformin works—it’s that, if it gets off the ground, it will be proof-of-concept for future studies. “We’re doing this study to convince the FDA that aging can be targeted,” Barzilai says. “I do think delaying aging can be done within the next decade.” If metformin ends up working, great. If it doesn’t, then the next drug tested for its anti-aging properties—or the one after that—will.
TAME is structured like most other controlled, randomized clinical studies used to test drugs for diseases like diabetes or heart failure. The study will recruit approximately 3,000 elderly people; half will receive metformin and half will be given a placebo. The drug’s success will be gauged by its ability to delay the onset of afflictions associated with the aging process: cardiovascular disease, cancer and cognitive decline. Because the TAME study targets diseases associated with aging rather than the number of years a person lives, it is technically less about extending life spans than it is about extending “health spans”—making the years at the end of a person’s life healthier. The upshot could, of course, be longer lives, because healthier bodies tend to stick around longer.
One reason Big Pharma might not be so hot on TAME is that if it is successful, it could upend the pharmaceutical business. “The vast majority of older adults have multiple chronic conditions,” says Dr. Mary Tinetti, a professor of geriatrics at Yale University. FDA approval of metformin as an anti-aging medication “would encourage investigators to look at treatments that affect multiple conditions.” That matters because most elderly people typically face numerous health issues and require a plethora of pills. A person with both diabetes and heart disease, for example, might be taking a daily anti-diabetic agent, nonsteroidal anti-inflammatory, beta blocker and statin. If metformin—or some other single, cheap drug—can target multiple comorbidities in aging populations, it would significantly reduce the number of medications people need to take. Replacing all those with one would save patients money but would also cut deeply into pharmaceutical companies’ bottom lines.
Cutting down the number of drugs a patient takes other advantages: Medications prescribed for chronic conditions can have relative contraindications—they can cause serious side effects when taken with other medications, or impair the effectiveness of another drug. For instance, some arthritis drugs can make blood pressure medications less effective.
The TAME study would also pave the way for more extensive aging studies. When aging becomes a viable condition that pharma companies can target, that will encourage exponentially greater research in the field and hopefully result in new insights into the correlation between aging and chronic disease, explains Stephanie Lederman, the director of AFAR. This has the potential to be the space where Big Pharma could make the money it craves: Once pharma companies get involved, Lederman says, they will likely be able and willing to develop drugs that tackle aging even more effective than metformin.
But to get this all going, someone’s going to have to put up some initial funding. The TAME study is still projected to cost about $65 million, because of the price of recruitment and tracking the health of 3,000 people over six years. Without the backing of a major corporation, it might be a long time before Barzilai and his colleagues have the necessary resources to move TAME forward.
If it gets going, there will be a lot riding on TAME. The last time a leading drug company spent big bucks on anti-aging, they regretted it: In 2008, GlaxoSmithKline invested $720 million in a biotech startup developing drugs based on resveratrol, a compound found in red wine that appeared to increase life span in animal studies. The drug bombed in clinical trials, and GSK closed down the operation. If TAME gets off the ground but fails to produce the desired results, it’ll mean another big miss for anti-aging studies and could further discourage Big Pharma from hurrying back into the field.