Is This Really Possible? Legend has it that, more than 500 years ago, Ponce de Leon sought what Florida natives believed was the Fountain of Youth. Of course, no such fountain was found. Yet, that hasn’t discouraged people to search for ways to extend human lifespans. Over the past five centuries, this has been a fruitless endeavor. However, recent scientific breakthroughs have recently led to the birth of a number of new companies seeking to increase human longevity – companies with some big name backers like Jeff Bezos. Leaders of these start-ups have, in fact, made meaningful strides in uncovering new biological mechanisms that they believe can lead to drugs that will increase human longevity by at least a decade.
One particularly promising approach involves partially reprogramming our epigenome which dictates the expression of genes. In doing so it is hoped that the damage done to cells by environmental factors as well as things like obesity and diabetes can be reversed thereby providing treatments for age-related diseases. This all sounds terrific. However, there is a major challenge for discovering and developing anti-aging drugs. How does one design a clinical trial to convince patients, physicians, payers and, especially, the FDA that your drug actually works?
To do this, a company would have to prove that their drug extends lives. You can’t test such a drug in young or even middle-aged people as these groups still have considerable life left assuming a life-expectancy of 80 years. Thus, you would probably need to study the drug in healthy 70 year-olds (with a placebo control group as comparator) and then follow these subjects for a decade or more to see if those on drug live meaningfully longer than those in the placebo group. In order to see a statistically meaningful longevity effect, however, the study would need a minimum of 20,000 subjects. This “outcomes” trial would be similar to what is now done for new drugs to treat heart disease in which a drug’s efficacy is determined by whether it reduced heart attacks and strokes. Such studies are not cheap and the costs can be on the order of $2 billon.
The FDA would likely set a very high bar for safety and efficacy for such a study. Unlike studying patients with heart disease, here you would be testing your drug on 70 year-olds who are relatively healthy. Yet, these patients are entering a decade when they become more susceptible to various cancers, neurological disorders, cardiovascular diseases, etc. You would have to be certain that your drug was no different from placebo when studying these safety parameters. The FDA’s caution would be well justified. Such a drug would be in tremendous demand should it actually work. Should such a drug be approved and then later shown to increase major side-effects, the fall-out would be unprecedented.
And then, of course, you must convince payers to reimburse for such a drug – a drug that will probably command a high price. Payers would set a high bar as to who should be eligible for such a drug much as now happens with the PCSK9 inhibitors, the potent LDL-cholesterol lowering drugs which have been proven to reduce heart attacks and strokes in patients with heart disease.
Given these enormous challenges, why would anyone actually engage in anti-aging R&D drugs? After all, the people investing in these field are accomplished scientists and investors. They are aware of these challenges. Despite the hype around extending the human life-span by 10 -20 years, these companies will not look to conduct life extension studies right out of the gate. Rather, the first drugs will be tested against age-related diseases. For example, one company, Life Biosciences, hopes to use its work in epigenome reprogramming to treat strokes that occur in the back of the eye – a condition known as non-arteritic anterior ischemic optic neuropathy. While a new treatment for this disease would be welcomed, it is a far cry from adding a decade to the life-expectancy of baby boomers.
So, when reading the hype about new scientific breakthroughs that offer the promise of the “Fountain of Youth”, admire the science. But keep in mind that it’s going to be a long while before such drugs are actually available.
(John L. LaMattina is the former president of Pfizer Global R&D and the author of “Pharma & Profits – Balancing Innovation, Medicine, and Drug Prices”.)