Perhaps it is being driven by baby-boomers who are now facing their own mortality, but there has been a surge in activity in biotech companies looking for a ”fountain of youth” pill – a drug that would extend a person’s lifespan. There are a number of hypotheses emerging around novel biological mechanisms that possibly could do just that. For example, Elevian is exploring a protein known as growth differentiating factor 11 (GDF11) which, according to Elevian’s website, when infused into old mice can improve exercise capacity, improve brain function and accelerate muscle repair. Another prominent player in the anti-aging field is Elysium Health, which believes that boosting one’s NAD+ levels leads to an increase in longevity genes. In fact, Elysium sells an OTC nutritional supplement intended to do just that. But, the clinical benefit of this supplement is as yet unproven.
These companies are not run by charlatans. Rather, they are led by prominent researchers at academic institutions like Harvard and MIT. However, despite encouraging early stage studies in mice, skeptics question the viability of such work. In an article entitled “A ‘Fountain of Youth’ Pill? Sure, if You’re a Mouse”, Marisa Taylor of Kaiser Health News challenges this work. For one thing, she is concerned that the animal studies reported to date have not been easy to replicate. Furthermore, she worries that the hype is far too premature. Perhaps such a pill is on the horizon, but we’re still facing a long, laborious process to get there.
Nowhere is this challenge greater than running a clinical trial to prove a drug’s anti-aging properties. You would need to run a randomized clinical trial in an older population with half on drug and the other half on placebo. But how do you choose the patients? If they were on the younger side, say in their fifties, you’d have to study them for a long time to demonstrate a longevity effect as their life expectancy is still high. So you would likely need an older population to study. Since you are looking at extending life, the study endpoint is death. Such a study would require thousands of patients in order to get results that are statistically significant. Thus, to mimic the mouse studies in humans, you may need to run a 5 – 8 year study in thousands of patients and measure clinical outcomes. These types of studies have been done with cholesterol lowering medications and diabetes drugs to prove to regulators and payers that lowering LDL-cholesterol or HbA1c is actually extending life. Thus, these types of longevity experiments have precedence. But these trials are expensive and normally cost hundreds of millions of dollars.
To make things even more difficult, the FDA would require that your longevity drug exhibit a high degree of safety as these drugs would presumably be given for the rest of one’s life. This would send warning signals to payers as suddenly millions of people seventy and above would be clamoring for access for such a drug. Thus, they would set up very high hurdles to justify reimbursement for the cost of the longevity pill, as they have done with the PCSK9 cholesterol lowering drugs.
These challenges haven’t dissuaded at least one researcher from diving headlong into this arena. Dr. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine, has designed an anti-aging study called “Targeting Aging with Metformin” (TAME). Metformin is an antidiabetic drug that was approved by the FDA more than 70 years ago. It is still widely prescribed and its safety is well established. And, while its mechanism-of action is not known, it has been shown to extend the lives of nematodes by 57% and mice by 6%. Barzilai and colleagues have met with the FDA and designed TAME based on their input. TAME will consist of 3,000 patients between 65 – 79 years old and have a composite primary endpoint of myocardial infarction, stroke, heart failure, cancer, dementia and death. TAME is powered to detect a 22.5% reduction in the time to first incidence of any endpoint. Unfortunately, Barziali and his team have been struggling to raise the funds for this study. The American Federation for Aging Research has committed $35 million and they are hoping for another $40 million from the NIH. However, it is uncertain that such a relatively modest amount of funding will be appropriate for this type of study.
It is interesting to note that the big pharmaceutical companies like Pfizer, Merck and Novartis are shying away from anti-aging research. It could be that they are leery about entering an area that requires a long-term and expensive commitment in a field where the pay-off is years away. Nevertheless, anti-aging research is going to continue. The science is important and holds promise. But an anti-aging pill available for the masses is not around the corner. It might not even appear in our lifetime.