On May 27, 2026, the Reagan-Udall Foundation for the FDA, working alongside ARPA-H and the XPRIZE Foundation, ran a full-day public meeting on gerotherapeutic drug and biologic development. Strip away the dense regulatory jargon, and it was the exact conversation the longevity industry has needed for years: a direct discussion between developers and regulators on how to translate geroscience into approvable human clinical trials.
Video, slides, and transcripts have just been posted and I went through them with an eye for insights on getting a FDA approval. (I do drug development but not related to longevity.) For anyone who follows longevity research, the science on display was largely familiar. What is new is that regulators gave specific, on-record statements about what they will and will not approve.
Why the FDA won’t put ‘aging’ on a label
Perhaps the clearest lesson of the day came from Lisa Yanoff, a Deputy Director in CDER’s Office of Cardiology, Hematology, Endocrinology, and Nephrology, which is one of the review offices that approves drugs. She said FDA can approve a drug to improve a specific measured thing, for example VO2 max plus a walk test plus a cognitive measure, but the agency is “not going to go ahead and call that aging in a vacuum.”
It seems the agency’s framework will continue to run on three words: feel, function, survive. A drug earns an approval by showing it changes how a patient feels, how they function, or whether they survive. A biological age clock ticking down is a surrogate biomarker, not a clinical endpoint and, absent a major shift in how the agency thinks, will not help with approval.
Stepping-stone indications are a plausible path
If you cannot get approved for aging, you get approved for a disease first, then expand. James Peyer of Cambrian Bio laid out a clear version of this. You start with a mechanism that extends healthy lifespan in animals, you pursue an actual disease with an accepted endpoint in humans, a stepping-stone, and only then do you reach toward the broad preventive use that is the real prize.
From the FDA’s way of seeing things, as Peyer put it, “a gerotherapeutic is just a preventative medicine,” only one that prevents more than one disease. The agency has no difficulty approving preventive medicines. The market failure is that prevention trials take a long time and run long, so private money avoids them as first indications. Stepping stone indications solve the money problem by getting approval and revenue within a reasonable budget.
BioAge offered the legislative version of the same idea, a Kitalys Institute proposal. The THRIVE Act would create a new “Healthspan Product” category for drugs that prevent or reverse two or more age-related diseases, with incentives modeled on rare disease and regenerative medicine. If it passes, it changes the economics of exactly the repurposed and preventive plays that are otherwise hard to fund. But the vast majority of proposed bills never become law, so at this point I’d watch it without betting on it.
Peyer also described what he calls the metabolic shortcut. The FDA already accepts that exceeding 5% weight loss in a 52-week study can support an obesity approval, and obesity, like aging, is not a classical disease but a risk factor for many diseases. So a gerotherapeutic that drives weight loss can get approved in that lane immediately and expand to non-obese people later. Most drugs do not get a shortcut like that, which is why the endpoint problem is the heart of everything.
Intrinsic capacity: a solution to the endpoint problem
Jeffrey Siegel, the CDER office director who oversees biomarker and clinical outcome assessment qualification across all therapeutic areas, discussed potential gerotherapeutic endpoints. When industry says “biomarker,” it usually means surrogate endpoint, and to use a surrogate for approval you have to show that a change in it predicts a later clinical outcome, which normally needs randomized trial evidence. His view was that getting a biomarker validated as a surrogate is “going to be a long time before we get there.” This is because you need already-effective therapies to generate that evidence, and the field does not yet have them. What you can do now is show a biomarker sits on the causal pathway of disease, which strengthens an evidence package without being a surrogate on its own. By this reasoning, clocks are years off from being useful for approval. So if not clocks, what?
The consensus answer was Intrinsic Capacity (IC). IC is a WHO framework that evaluates a patient across five core domains:
- Locomotor (movement, grip)
- Cognitive (memory, executive function)
- Psychological (mood, resilience)
- Sensory (vision, hearing)
- Vitality (metabolic/immune balance)
Because these domains measure things patients actually experience, IC possesses the immediate face-validity that biological age clocks lack. Furthermore, there is already an ICD-11 code (MG2A) for age-associated decline in IC, providing a recognized diagnosis to anchor a context of use.
This shift toward multi-domain, functional endpoints addresses a historical trap in geroscience trial design. Historically, indications like sarcopenia have been notoriously difficult to clear because a drug might successfully increase muscle mass (a surrogate biomarker) but fail to improve walking speed or grip strength (a functional endpoint). If a drug doesn’t change how a patient feels or functions, the FDA cannot approve it.
A composite like this is not a free lunch, as trialists at the meeting emphasized. Stephen Kritchevsky noted that bundling more components into an endpoint raises the event rate, which means shorter trials or smaller samples, but if the drug does not move every component the overall effect gets diluted and the trial loses power. David Allison pressed the related problem that the weighting of a composite is an analyst’s choice rather than a fact, so two reasonable people can score the same trial differently. This is why the near-term consensus is to read IC at the domain level rather than leaning on a single global number.
ARPA-H’s PROSPR program is betting on IC precisely because of that face validity, and is funding collection of the data sets to back it. The THRIVE team (Stanford, the Buck, and others) is building a “PROSPR IC Score” from more than 20 longitudinal cohorts and submitting it to the FDA as a clinical outcome assessment through the drug development tool pathway, while separately developing an at-home IC test kit (app, wearable, blood micro-sample, AI score) through the device De Novo route. Those two routes are not the same bar. Clearing the kit as a measurement device is a far lighter lift than qualifying IC as a drug-approval endpoint, so an authorized at-home longevity tracker would not, by itself, give anyone an approvable endpoint for a therapeutic. An ARPA-H consensus on IC already exists, and its near-term recommendation is conservative: use IC at the domain level (locomotor, cognitive) as primary or secondary endpoints, not as one global score, and not yet as a validated surrogate.
The structural pitch underneath all of this is the “Adult Health Curve.” John Beard made the case with a pediatric analogy. Just as a pediatrician plots a child against a growth curve and intervenes when the trajectory deviates, adult medicine could plot a person’s intrinsic capacity from midlife onward and treat functional decline as a condition to act on before chronic multimorbidity sets in. THRIVE’s plan explicitly includes generating that normative curve, which will give the field a familiar framing to hand the FDA rather than a novel one to argue from scratch.
The roadmap, then, is not to validate a longevity biomarker. It is to build a functional endpoint that the FDA can already accept using the feel-function-survive framework, and generate the longitudinal data to make it credible. ARPA-H, XPRIZE, and the THRIVE team are working in parallel with the drug programs, because, as was repeatedly noted, bone mineral density took roughly a decade to qualify and nobody wants to retrofit endpoints after the trials are done.
Starting points: frailty, sarcopenia, and immune function
Frailty and sarcopenia came up repeatedly as ideal stepping stones, and the former FDA people and ARPA-H agreed. They are serious conditions with real unmet need, which is the criterion for accelerated approval. Andrew Brack of ARPA-H made a strong case: frailty maps onto low intrinsic capacity, and frail patients have roughly a 40% five-year survival, in the same range as ovarian cancer. As he put it, that is your mortality experiment. Sarcopenia now carries a disease code, and David Glass of Regeneron argued that simply preventing age-related muscle loss should be approvable on its own, the way bone density eventually was. Yanoff separately flagged sarcopenia as an area where the FDA is close enough to a definition to give useful input.
The third starting point, immune function in older adults, may be the one most likely to interest anyone following rapamycin. Joan Mannick, now at Altos, walked through the mTOR-inhibitor immune program (the RTB101 lineage) that this field has followed closely. The clinical lesson she drew is directly actionable: improving immune function in older adults, measured as the incidence or severity of respiratory tract infections, is a feasible regulatory path. But after the FDA pushed her program toward a softer, symptom-based endpoint that then failed, her conclusion was that it is critical that “lab confirmation be used as part of the endpoint, not just symptoms.” So “improve immune function in the elderly” is arguably the most concretely approvable construct in the whole space, and it is an mTOR story.
Then Cambrian’s Peyer described TOR-101, an mTORC1-selective inhibitor that, in their data, hits mTORC1 hard at every dose while never touching mTORC2. Cambrian claims no immunosuppression even at 100-fold higher exposures than where you normally see it, and benefits across cardiac, cancer prevention, and vaccination response. Their plan with PROSPR is to use a vaccination-response stepping stone in older adults, then move directly into an intrinsic-capacity study, shaving an estimated five to ten years off the timeline to a preventive indication.
Generic rapamycin itself remains in the mix as a repurposed agent: it is one of the three drugs (with semaglutide and the SGLT2 inhibitor dapagliflozin) that UT San Antonio is running in its ARPA-H VITAL-H healthspan trial, and Mount Sinai’s XPRIZE finalist program pairs weekly rapamycin with spermidine and exercise. The drug many in the community already take is now the substrate for multiple formal, FDA-facing programs.
FDA advice to sponsors
Four points stood out to me from FDA statements.
First, come in at the IND stage with a specific proposal. Yanoff was clear about how things move fastest: a sponsor arrives with a specific product and specific questions and the FDA is on a user-fee clock to respond. She suggested a reasonable, well-justified proposal gets a yes more often than people expect. You can of course file an IND on a repurposed drug you do not have a patent on. And for pre-product concepts there are cheaper Critical Path Innovation Meetings that can include non-industry participants.
Second, use the framework that already exists, and use the cost-savers in it. Justin Penzenstadler, the nuts-and-bolts reviewer on the panel, said he sees “no impasse towards getting this across the finish line” if you can clearly define a population and reliably measure benefit and risk. Hard endpoints like overall survival and disability-free survival are ready today, TAME-style, and the agency already uses model-based methods to translate hazard ratios into years of survival. For the repurposing approach, his most useful tip was ICH E19, the guidance on selective safety data collection: you do not need exhaustive safety labs on a well-characterized old drug, and designing around E19 strips out cost and logistics. His parting advice was the same three words: feel, function, survive. Keep your endpoint face-valid and you need far less validation than a surrogate like LDL or bone density required.
Third, get the review division to want your endpoint. Siegel explained that the qualification programs sit separate from the review divisions but work hand in glove with them, and that biomarkers move fast only when a review division actively pushes. His worked examples were bone mineral density for osteoporosis and the non-invasive tests for MASH, where the FDA published the process and now has submissions in flight. He emphasized this sequence: agree on what the disease or disorder is first, then talk endpoints and biomarkers. Define the condition, then the measure.
Fourth, expect the bar to be set by the most thorough sponsor. Yanoff pointed to cachexia, another multifactorial condition without a clean single definition, as a template for how a multi-domain construct could eventually be approved: the FDA’s approach there is to require effects across several aspects (appetite, body weight, a meaningful functional measure), which is plausibly how intrinsic capacity earns acceptance over time. She paired it with a competitive warning. The agency treats similarly situated sponsors fairly, so if you measure one domain and a competitor measures three, you will not both get the same broad claim. The field tilts toward whoever does the most complete work.
Former CDER reviewer Sandra Kweder delivered a useful reminder, noting that the biggest gap she saw all day was safety. When she reviewed the slides in advance, she said, “all I saw was well tolerated. That’s not enough.” The agency wants off-target effects and the downsides of on-target effects spelled out. Dose selection is uniquely hard when the real outcome is years away, and we cannot assume a dose validated for one indication has the same profile in an older, sicker population.
Putting it together
The destination is not an “anti-aging” label. It is a series of specific, function-based approvals that add up to gerotherapeutics by another name. We get there by picking a stepping-stone indication the FDA already accepts, with frailty, sarcopenia, and immune function in older adults being the conditions the agency signaled openness to. We anchor trials in face-valid functional endpoints, with intrinsic capacity at the domain level as the rallying point, and we treat biological age clocks as enrollment and mechanism tools, not registrational endpoints. We engage at the IND stage with a specific, well-justified proposal rather than waiting for consensus, exploit cost-savers like ICH E19 when repurposing, and work to get a review division to actually want the endpoint. In parallel, the field builds the shared infrastructure (the PROSPR IC score, the at-home kit, pooled longitudinal cohorts, proteomic panels) that no single company will fund alone, because that is the public-good layer everyone will rent.
None of this binds the FDA to anything, and the people most eager to call a path open are usually the ones with money riding on it. Optimism about the THRIVE Act and fast timelines should be weighed accordingly, as the sitting CDER officials were careful to say the science is still mostly upstream of where the agency can act. But the field spent years unsure how the agency would engage with aging. Now its own reviewers have said, on the record, what they will accept: a real indication, a population they can define, and evidence that someone feels, functions, or survives better. That is a more tractable ask than reversing aging, and it is more than the field had before.