A charitable view of the FDA is that it is populated by well-meaning people who happen to believe that (a) any cost in lives, time, and funds is worth it in order to prevent harm by commission, and (b) zero risk is a possible goal in medicine. The Hippocratic Oath Enforcement Agency, if you like. There are much less charitable views, given the present state of regulatory capture that dramatically raises costs and slows development, as well as the invisible graveyard of countless lives lost to the absence of medical technologies that would otherwise exist and be widely available at reasonable prices.
There is no established regulatory path to approval for treatments that target aging. So at present biotech and pharma companies working on therapies that target mechanisms of aging pick a single age-related disease in order to gain regulatory approval. It is assumed that there will be widespread off-label use thereafter. There are efforts underway to pave a better road, but this will take a good long time at the usual glacial pace of large regulatory agencies.
An endocrinologist by training, Kitalys Institute founder Alexander Fleming is well qualified to take on the regulators. He spent more than a decade at the FDA, where he led the medical reviews that resulted in approval of drugs including metformin, as well as the first statin, insulin analog, and PPAR agonist. Getting approved longevity and geroscience therapies into the public domain is what Kitalys and its conferences and initiatives are all about. No easy task, as Fleming is all too aware. "I think we have some unique challenges in the geroscience domain, in particular the kind of evidence that will be required for regulatory approval. It's going to take a much longer clinical trial to get the evidence to show that the product is working, and not just on the typical endpoint that would be used to approve a drug."
One of the key challenges in geroscience and interventions that target aging is that, unless an intervention truly reverses a disability or something that people already are experiencing, then it will require very long studies to show the benefit. The first such longevity trial, the TAME trial on metformin, is about to commence, led by Nir Barzilai. "Nir and his colleagues are about to embark on a trial that could run three to five years to show an effect across multiple chronic diseases. But here's the thing - we can't expect metformin to produce more than very small effects in slowing the onset of each chronic disease. The premise of the TAME trial is that putting these small effects together in a composite endpoint will show that metformin is doing something sooner than it would be possible to demonstrate an effect on the individual diseases. Still, these effects, even when summed will never be noticed by the individual. But that is what we need - we need that data. So, that's really what we're striving to do - to create an environment that will produce that data. Part of that is having clear regulatory pathways that define the goal posts."
Kitalys is already engaged in what he considers to be two major educational projects. "One is to the regulatory authorities themselves. It's not that they are antagonistic to the development of geroscience products. They are enthralled by the science, but they're scratching their heads as to what they're being asked to do. So, we want to help them on that front. The other educational project involves the people on the other side, particularly those either in the lab or trying to do translational work, and who feel that the regulators are part of the problem. And that's not really true - the regulators are simply reflecting the reality that it takes a long time to get evidence to justify approval of products that may require decades of individual use to provide full benefit." Fleming believes that both sides need to understand each other's predicament and challenges.