Lifespan Research Institute proposes reusing safety data for aging therapies across diseases and accepting validated measures of biological age as evidence of efficacy

Lifespan Research Institute proposes reusing safety data for aging therapies across diseases and accepting validated measures of biological age as evidence of efficacy

On October 26, Lifespan Research Institute (LRI) released a report by Lifespan.io editor-in-chief Steve Hill on how to evaluate therapies that target multiple age-related diseases.

Drug regulation is designed around a drug with one mechanism targeting one disease, whereas aging therapies, Hill argues, act on mechanisms shared by many diseases. He writes that understanding aging and developing treatment technologies are no longer the main bottlenecks: “The limiting constraint is now regulatory and institutional.”

Partial cellular reprogramming is one example. The report does not name a drug, but the trials it mentions in two optic nerve diseases are being conducted by Life Biosciences. Its ER-100 temporarily activates three genes intended to restore more youthful gene expression in retinal nerve cells, and the first human data were released in October. According to LRI, applying the technology to type 2 diabetes or heart failure would require an almost entirely separate clinical data package, renewed safety testing, and agreement on the endpoints used to assess efficacy.

LRI proposes allowing safety data to carry over when the technology is applied to other diseases, treating improvements in delivery or manufacturing as refinements of the same drug, and accepting validated surrogate endpoints alongside disease-specific outcomes. These surrogates would include epigenetic clocks (which estimate biological age from marks on DNA) and measures of organ function.

The report cites the ARDD conference, where, on October 1, the FDA announced aging as a regulatory science priority. There, the FDA’s Justin Penzenshtadler outlined his expectations: the first trials capable of supporting approval would assess age-related diseases or mortality, while collecting functional assessments alongside them so that these measures could later be linked to outcomes. He favors starting with older people at high risk, since healthy people would require prolonged treatment: “We are thinking about potentially treating someone for thirty years to gain a couple of years.” The conference discussion described three steps toward establishing a measure as a surrogate endpoint: the measure is associated with outcomes, changes in the measure are associated with changes in risk, and treatment-induced changes in the measure predict outcomes in trials.

Of the existing approval models, the report appears to favor Japan’s legal framework. It allows regenerative medicine products to receive conditional, time-limited approval when safety has been established and efficacy can reasonably be predicted. Data collection is mandatory after market entry, and a decision on full approval is made at the end of the approval period. HeartSheet, sheets of a patient’s own muscle cells used to treat heart failure, received conditional approval in 2015, and the approval period was extended. In July 2024, a health ministry advisory council concluded that efficacy had not been demonstrated, and the manufacturer, Terumo, announced that it would discontinue sales.

A4LI, LRI’s sister organization, has included a special designation in a draft amendment to the Food, Drug, and Cosmetic Act for a drug whose mechanism is shared by two or more age-related diseases in different categories. Under the proposal, such a drug would be assigned a joint team from FDA divisions and would be eligible for a single trial protocol. The proposal would also require the FDA to issue guidance on functional assessments, such as measures of a person’s abilities, as surrogate endpoints. The amendment is proposed for inclusion in PDUFA VIII, the reauthorization of the law governing fees for reviewing drug applications; the “breakthrough therapy” designation was introduced through this route in 2012.