June 17, 2015

On June 24, FDA will meet with researchers to consider a clinical trial which treats aging as a disease target

Doctors and scientists want drug regulators and research funding agencies to consider medicines that delay ageing-related disease as legitimate drugs. Such treatments have a physiological basis, researchers say, and could extend a person’s healthy years by slowing down the processes that underlie common diseases of ageing — making them worthy of government approval. On 24 June, researchers will meet with regulators from the US Food and Drug Administration (FDA) to make the case for a clinical trial designed to show the validity of the approach.

Current treatments for diseases related to ageing “just exchange one disease for another”, says physician Nir Barzilai of the Albert Einstein College of Medicine in New York. That is because people treated for one age-related disease often go on to die from another relatively soon thereafter. “What we want to show is that if we delay ageing, that’s the best way to delay disease.”

Barzilai and other researchers plan to test that notion in a clinical trial called Targeting Aging with Metformin, or TAME. They will give the drug metformin to thousands of people who already have one or two of three conditions — cancer, heart disease or cognitive impairment — or are at risk of them. People with type 2 diabetes cannot be enrolled because metformin is already used to treat that disease. The participants will then be monitored to see whether the medication forestalls the illnesses they do not already have, as well as diabetes and death.

On 24 June, researchers will try to convince FDA officials that if the trial succeeds, they will have proved that a drug can delay ageing. That would set a precedent that ageing is a disorder that can be treated with medicines, and perhaps spur progress and funding for ageing research.

During a meeting on 27 May at the US National Institute on Aging (NIA) in Bethesda, Maryland, Robert Temple, deputy director for clinical science at the FDA’s Center for Drug Evaluation and Research, indicated that the agency is open to the idea.

Fightaging.org does not think this effort will achieve any useful regulatory decision or change for many years. He cites the example of the effort to get Sarcopenia ruled a disease. Sarcopenia is muscle loss due to old age. It is to muscle as osteoporosis is to bone.

Lobbying the FDA to consider Sarcopenia a medical condition and thus allow commercialization of treatments in the US has been underway for a long time indeed, with no sign that FDA bureaucrats are going to do anything more than continue to hold meetings, request expensive data, and waste time.

I think that the better road ahead is to commercialize treatments outside the US on the back of a strong medical tourism industry. The stem cell marketplace could grow into that, but has yet to organize to the point at which it can influence the research community sufficiently to close the funding circle. It absolutely should be any US researcher's expectation that their primary and best avenue for commercial application of medical research is outside the US. Further, a robust trade on that front is the only way to drive back the ever-increasing demands of the FDA. Regulatory competition with other regions is the only argument that bureaucrats reliably listen to: the point at which they look like fools for holding out further. I expect we'd still be waiting on legalization of stem cell treatments of any sort in the US if they hadn't been widely available for years in reliable clinics and hospitals across both land borders and the Pacific.

Organizers of the TAME trial think that the field is now in a better position because animal studies have shown that some drugs and lifestyle practices can extend life by targeting physiological pathways1.

For instance, the NIA-sponsored Interventions Testing Program, in which investigators at three sites are systematically trialling candidate age-delay treatments, has shown that a handful of interventions convincingly and reproducibly prolong the lives of various strains of mice. Those include cutting down on calorie intake and taking a drug called rapamycin that is used to prevent rejection of transplanted organs.

And researchers from the Novartis Institutes for Biomedical Research in Cambridge, Massachusetts, reported in December that elderly people develop a stronger immune response to an influenza vaccination if they also take a rapamycin-like drug2. Rapamycin, which acts on a biological pathway involved in cell growth, is now seen as one of the most promising drugs for delaying ageing, but given over long periods of time it also suppresses the immune system

Safety first

The TAME test is for metformin, which suppresses glucose production by the liver and increases sensitivity to insulin. The drug has been used for more than 60 years and is safe and prolongs healthy life and lifespan in worms3 and in some mouse strains1. Data also suggest that it could delay heart disease, cancer, cognitive decline and death in people with diabetes4. Plans call for the trial to enrol 3,000 people aged 70–80 years at roughly 15 centres around the United States. The trial will take 5–7 years and cost US$50 million, Barzilai estimates, although it does not yet have funding.

Matt Kaeberlein at the University of Washington, Seattle, who is running a trial of rapamycin in elderly dogs, says that the concept behind Barzilai’s trial is sound. Even though other drugs might be more effective at delaying ageing in animal studies, he says, the many years of experience with metformin in people, combined with data suggesting that it impacts the ageing process in people, make it a good candidate for a first clinical trial in the field.

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