XPRIZE Healthspan director: Evidence is still needed for regulatory discussions that assess aging treatments through muscle, cognitive and immune function, and the $101 million competition is generating it through shared protocols

XPRIZE Healthspan director: Evidence is still needed for regulatory discussions that assess aging treatments through muscle, cognitive and immune function, and the $101 million competition is generating it through shared protocols

The XPRIZE Healthspan prize will go to a team whose treatment restores muscle, cognitive and immune function within a year to levels seen 10–20 years earlier. On October 26, competition director Jamie Justice and jury chair Steven Cummings, an epidemiologist, explained how that result is measured on the Longevity.Technology podcast. Fellow judge Phil Newman asked the questions.

Newman asked what measurements taken over a year can tell us about decline over 10–20 years. Justice replied: “Do we currently have the evidence needed for a regulatory discussion based on function? No.” The competition keeps trials below phase three, which usually marks the start of the path to approval, to limit the regulatory burden on teams. For the FDA, a drug’s benefit concerns how a person feels, functions and survives. A one-year trial will not show outcomes such as loss of mobility or new diseases. Justice says, however, that changes in function over a year can be used in a model to estimate how those outcomes would change.

Ten of the twenty finalist teams received $1 million each. Teams run trials at their own sites but share a laboratory, tests and a data center, allowing the judges to compare results directly. The competition covers these costs for the ten grant recipients, providing $2–2.5 million in shared resources per team. A conventional grant funds the effort, Justice says, while a prize pays for “proof and demonstration.”

Muscle function is assessed with a six-minute walk, cognitive function with attention and memory tests, and immune function with blood tests. Each participant’s improvement is compared with an individual threshold corresponding to the typical decline over 10, 15 or 20 years among people of the same age, sex and baseline function. To win the grand prize, a team must show that, in each of the three domains, the proportion of treated participants who exceed that threshold is greater than the proportion in the control group by a prespecified amount. Under the competition rules, the prize increases with the threshold: $61 million for ten years, $71 million for fifteen and $81 million for twenty. Typical declines in muscle and cognitive function by age and sex are estimated from long-term observational data through a grant program run by XPRIZE and the American Federation for Aging Research. Justice says XPRIZE is already receiving requests for its protocols and decline thresholds.

Cummings divides the evidence into two parts: what the treatment changes, and whether that change predicts outcomes that matter to the FDA. For the first, he advises companies to use the competition’s measurements. Establishing the second is the next step. A change in a measured indicator can diverge from the clinical outcome. In the ACCORD trial, cited in a 2022 paper by Cummings and a coauthor, intensive treatment of people with diabetes reduced average blood sugar levels, but mortality increased.

Cummings, whose trials supported the development of several widely used osteoporosis drugs, identifies two risks for the teams. The first is safety: potent treatments carry a higher risk of serious side effects, and effective osteoporosis drugs have failed for this reason. One strengthened bones but increased the risk of stroke. The second is recruitment: if a trial falls short by a hundred participants, even a “real gem” may fail to show its value.

Justice adds that people age differently, citing a saying: “The same boiling water that softens a potato hardens an egg.” She suggests that the winning approach may be a set of strategies tailored to risk groups and individuals, rather than a single drug for everyone.