Groundbreaking TAME trial, which directly targets aging as an endpoint, finally begins this November, reveals lead clinician Dr Nir Barzilai.

After closing the final $40m of its required $75m budget with a donation from a private source, the first drug trial directly targeting aging is set to begin at the end of this year, lead researcher Dr Nir Barzilai has revealed in an exclusive interview with Longevity.Technology.

Back in 2015, when his revolutionary anti-aging trial TAME finally received FDA approval, it would have been forgivable to think that Dr Barzilai had, at last, got past the hard part. But TAME went into financial limbo, with many wondering if it would ever be able to escape. “We wasted valuable time negotiating,” said Dr Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine,“but we’re finally on track.” His trial TAME (Targeting Aging with Metformin) had been stalled for four years while he and his colleagues engaged in funding negotiations with the US NIH (National Institute of Health).

“It was down to their conservative approach over there. They really didn’t understand what we were trying to achieve,” he said.

Longevity.Technology: Truly effective anti-aging pills are a long way away from full realisation. While a number of studies have demonstrated benefits conferred to patients both by metformin and rapamycin, not many expect the drugs to be highly effective at enhancing Longevity. The TAME trial’s green light is very good news for those who want to develop better Longevity drugs in the future. If the trial’s unique structure works, its completion in five years’ time could be the spur for many who have, so far, been discouraged from trialling drugs with aging as a direct endpoint.

The TRL score for this Longevity.Technology domain is currently set at: ‘Technology has completed initial trials and demonstrates preliminary safety data.’

The TRL score for the technology addressed in this article is: “Principles are demonstrated through experimentation.”

For those accustomed to judging the success of a drug trial’s funding acquisition by the safety and efficacy record of its drug, TAME’s funding difficulties could look confusing. Safely used and widely prescribed, the trial’s antidiabetic drug, metformin, has been US FDA approved since 1994. Its use in medical practice extends back into the Middle Ages, where it was extracted from the French lilac and later in France from the 1950s onwards, when the isolated compound was first successfully administered to diabetic patients.

But it is much more the trial structure, rather than the drug itself, that is on trial. Instead of following a traditional structure given to FDA approved trials (that look for a single disease-endpoint) TAME has a composite primary endpoint – of stroke, heart failure, dementia, myocardial infarction, cancer and death. Rather than attempting to cure one endpoint, it will look to delay the onset of any endpoint, extending the years in which subjects remain in good health – their healthspan.

Barzilai believes metformin is the perfect fit for a trial of this kind. In recent years it has been shown to extend the lives of nematodes (or roundworms) by 57% and mice by 6%. In humans, claims abound that metformin-takers are living longer, having fewer cardiovascular episodes and seeing reduced odds of getting cancer.

In a retrospective 2014 analysis [1] conducted by the University of Cardiff of 78,000 adult type 2 diabetics in their 60s, those who took metformin lived longer, on average, than healthy controls of the same age. This has led a growing body of doctors beginning to prescribe the drug off-label, so that their patients may benefit from its purported anti-aging effects.

Such widespread speculation demands deeper scientific investigation. It is TAME’s composite primary endpoint, created with the cooperation of the FDA, that excites Barzilai and his colleagues. They hope that Big Pharma will use it to develop drugs with even more powerful anti-aging effects. The NIH, however, was loath to sponsor a trial with such an unconventional format, and the off-patent status of metformin meant that, while its success would be an excellent win for the public and the Longevity field, few private investors took much interest in donating funds.

This was until the $40m donation, which made up more than half of the required funds for the trial. Steven Austad, scientific director of AFAR (American Federation for Aging Research) the organisation that provided the other $35m, says, “I’m incredibly pleased that TAME is going ahead. We want a pathway that we can use to target aging. Even if metformin doesn’t work, we’ve illuminated a route by which an anti-aging drug can get FDA approval in a relatively short-time frame study of four or five years. This will very likely interest Big Pharma.”

Whether metformin itself is a success or a failure, the trial will very likely revolutionise the way that aging research is done.

As for who provided the $40m funding, Barzilai remains coy, “I can’t tell you who gave us it, but it will be a great story one day!”

Dr. Barzilai’s exclusive interview with Longevity.Technology can be found here.

[1] https://www.ncbi.nlm.nih.gov/pubmed/25041462